Shifting Streets COVID-19 Mobility Data: Findings from a global dataset and a research agenda for transport planning and policy -
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+The COVID-19 pandemic brought a dramatic shift in demand for spaces for safe, physically distanced walking, bicycling, and outdoor commerce. Cities around the world responded by instituting a variety of policies and programs meant to address this shift, such as carving out roadway space for non-car uses, putting pedestrian walk signals on recall, reducing speed limits, and subsidizing bike share schemes. The extraordinarily rapid pace and global scale of these responses—and the public’s reactions to them—suggest that the transport planning, policy, and engineering professions may be at an inflection point with respect to equitable accommodation of non-car transport modes. In this paper we describe an effort to support potential shifts in practice by documenting and cataloging over a thousand COVID-19-related mobility responses into a publicly available database. We provide detailed guidance on using the database, along with preliminary summaries of key variables in the database. We also put forth a research agenda intended to build understanding about the processes that led to these actions, their implications for future efforts to design and implement pedestrian and bicycle infrastructure, and ways in which the transport professions might evolve in response to lessons learned during and after the pandemic.
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Extensive recombination-driven coronavirus diversification expands the pool of potential pandemic pathogens -
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+The ongoing SARS-CoV-2 pandemic is the third zoonotic coronavirus identified in the last twenty years. Previously, four other known coronaviruses moved from animal reservoirs into humans and now cause primarily mild-to-moderate respiratory disease. The emergence of these viruses likely involved a period of intense transmission before becoming endemic, highlighting the recurrent threat to human health posed by animal coronaviruses. Enzootic and epizootic coronaviruses of diverse lineages pose a significant threat to livestock, as most recently observed for virulent strains of porcine epidemic diarrhea virus (PEDV) and swine acute diarrhea-associated coronavirus (SADS-CoV). Unique to RNA viruses, coronaviruses encode a proofreading exonuclease (ExoN) that lowers point mutation rates to increase the viability of large RNA virus genomes, which comes with the cost of limiting virus adaptation via point mutation. This limitation can be overcome by high rates of recombination that facilitate rapid increases in genetic diversification. To compare dynamics of recombination between related sequences, we developed an open-source computational workflow (IDPlot) to measure nucleotide identity, locate recombination breakpoints, and infer phylogenetic relationships. We analyzed recombination dynamics among three groups of coronaviruses with impacts on livestock or human health: SARSr-CoV, Betacoronavirus-1, and SADSr-CoV. We found that all three groups undergo recombination with highly diverged viruses, disrupting phylogenetic relationships and revealing contributions of unknown coronavirus lineages to the genetic diversity of established groups. Dynamic patterns of recombination impact inferences of relatedness between diverse coronaviruses and expand the genetic pool that may contribute to future zoonotic events. These results illustrate the limitations of current sampling approaches for anticipating zoonotic threats to human and animal health.
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Codon arrangement modulates MHC-I peptides presentation: implications for a SARS-CoV-2 peptide-based vaccine -
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+Among various vaccination strategies, peptide-based vaccines appear as excellent candidates because they are cheap to produce, are highly stable and harbor low toxicity. However, predicting which MHC-I Associated Peptide (MAP) will ultimately reach cell surface remains challenging, due to high false discovery rates. Previously, we demonstrated that synonymous codon arrangement (usage and placement) is predictive of, and modulates MAP presentation. Here, we apply CAMAP (Codon Arrangement MAP Predictor), the artificial neural network we used to unveil the role of codon arrangement in MAP presentation, to predict SARS-CoV MAPs. We report that experimentally identified SARS-CoV-1 and SARS-CoV-2 MAPs are associated with significantly higher CAMAP scores. Based on CAMAP scores and binding affinity, we identified 48 non-overlapping MAP candidates for a peptide-based vaccine, ensuring coverage for a high proportion of HLA haplotypes in the US population (>78%) and SARS-CoV-2 strains (detected in >98% of SARS-CoV-2 strains present in the GISAID database). Finally, we built an interactive web portal (https://www.epitopes.world) where researchers can freely explore CAMAP predictions for SARS-CoV-1/2 viruses. Collectively, we present an analysis framework that can be generalizable to empower the rapid identification of virus-specific MAPs, including in the context of an emergent virus, to help accelerate target identification for peptide-based vaccine designs that could be critical in safely attaining group immunity in the context of a global pandemic.
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Site-specific O-glycosylation analysis of SARS-CoV-2 spike protein produced in insect and human cells -
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+Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures. SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported. The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence difficult to predict. Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S – insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD). In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD. Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites. However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy. This suggests possible complimentary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
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Large-scale analysis of SARS-CoV-2 spike-glycoprotein mutants demonstrates the need for continuous screening of virus isolates -
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+Due to the widespread of the COVID-19 pandemic, the SARS-CoV-2 genome is evolving in diverse human populations. Several studies already reported different strains and an increase in the mutation rate. Particularly, mutations in SARS-CoV-2 spike-glycoprotein are of great interest as it mediates infection in human and recently approved mRNA vaccines are designed to induce immune responses against it. We analyzed 146,920 SARS-CoV-2 genome assemblies and 2,393 NGS datasets from GISAID, NCBI Virus and NCBI SRA archives focusing on non-synonymous mutations in the spike protein. Only around 13.6% of the samples contained the wild-type spike protein with no variation from the reference. Among the spike protein mutants, we confirmed a low mutation rate exhibiting less than 10 non-synonymous mutations in 99.98% of the analyzed sequences, but the mean and median number of spike protein mutations per sample increased over time. 2,592 distinct variants were found in total. The majority of the observed variants were recurrent, but only nine and 23 recurrent variants were found in at least 0.5% of the mutant genome assemblies and NGS samples, respectively. Further, we found high-confidence subclonal variants in about 15.1% of the NGS data sets with mutant spike protein, which might indicate co-infection with various SARS-CoV-2 strains and/or intra-host evolution. Lastly, some variants might have an effect on antibody binding or T-cell recognition. These findings demonstrate the increasing importance of monitoring SARS-CoV-2 sequences for an early detection of variants that require adaptations in preventive and therapeutic strategies.
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People with intellectual disabilities living in care facilities engaging in virtual social contact: A systematic review of the feasibility and effects on well-being -
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+During the initial phase of the COVID-19 pandemic, many people with disabilities living in care facilities could not receive visitors. The use of virtual social contact has been recommended by health authorities such as the World Health Organization. This systematic review examined the scientific evidence of the use and feasibility of information and communication technology (ICT) for social contact by people with intellectual disabilities living in care facilities, and potential effects on well-being.
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Is Commitment Getting Infected Too? How COVID-19 Stay-Home Orders Influence Workgroup Commitment -
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+The COVID-19 pandemic and associated “Stay-Home” restrictions in the United States have disrupted employees’ lives. We leverage the change brought on by the Stay-Home restrictions to examine corresponding changes in employees’ commitment to their workgroup. Specifically, we advance and test a model predicting that the Stay-Home restrictions prevented workgroups from engaging in rigidly performed, meaningful workplace activities (i.e., ritualistic workplace activities), which subsequently made members feel that the group was less cohesive and ultimately reduced members’ workgroup commitment. We also compare changes in workgroup commitment to changes in workgroup identification, hypothesizing that commitment to one’s group erodes more than identification when workgroups are perceived to be less cohesive. We test our model in a four-wave panel survey of 772 U.S. employees at the onset of the Stay-Home restrictions, which allows us to examine within-person changes to commitment over time. Consistent with our hypotheses, commitment decreased as the duration of Stay-Home restrictions increased, which was mediated by corresponding declines in engaging in ritualistic workplace activities and perceptions of the workgroup’s cohesiveness. Further, commitment to one’s workgroup declined more than did identification with the workgroup, due to the stronger relationship between perceived group cohesion and commitment (vs. identification). We replicated these results in a separate, preregistered cross-sectional survey. Our findings shed light on the mechanisms underlying workgroup commitment, demonstrating that engagement in ritualistic activities, which enhance workgroup cohesion, is linked to stronger commitment— more so than identification—over time.
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Targeted in situ cross-linking mass spectrometry and integrative modeling reveal the architectures of Nsp1, Nsp2, and Nucleocapsid proteins from SARS-CoV-2 -
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+Atomic structures of several proteins from the coronavirus family are still partial or unavailable. A possible reason for this gap is the instability of these proteins outside of the cellular context, thereby prompting the use of in-cell approaches. In situ cross-linking and mass spectrometry (in situ CLMS) can provide information on the structures of such proteins as they occur in the intact cell. Here, we applied targeted in situ CLMS to structurally probe Nsp1, Nsp2, and Nucleocapsid (N) proteins from SARS-CoV-2, and obtained cross-link sets with an average density of one cross-link per twenty residues. We then employed integrative modeling that computationally combined the cross-linking data with domain structures to determine full-length atomic models. For the Nsp2, the cross-links report on a complex topology with long-range interactions. Integrative modeling with structural prediction of individual domains by the AlphaFold2 system allowed us to generate a single consistent all-atom model of the full-length Nsp2. The model reveals three putative metal binding sites, and suggests a role for Nsp2 in zinc regulation within the replication-transcription complex. For the N protein, we identified multiple intra- and inter-domain cross-links. Our integrative model of the N dimer demonstrates that it can accommodate three single RNA strands simultaneously, both stereochemically and electrostatically. For the Nsp1, cross-links with the 40S ribosome were highly consistent with recent cryo-EM structures. These results highlight the importance of cellular context for the structural probing of recalcitrant proteins and demonstrate the effectiveness of targeted in situ CLMS and integrative modeling.
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Modulation of SARS-CoV-2 Spike-induced Unfolded Protein Response (UPR) in HEK293T cells by selected small chemical molecules -
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+Coronaviruses (CoV) exploits the endoplasmic reticulum (ER) of the host cells for replication and in doing so, increases ER stress. evokes Unfolded Protein Response (UPR) and possibly autophagy, which could all attribute to the pathophysiology of the viral infections. To date, little is known about the roles of ER stress, UPR, and autophagy in SARS-CoV-2 infection. Here we over-expressed the viral Spike (S) protein in cultured HEK293T cells, as it has been shown that such protein is largely responsible for UPR activation in other CoV-infected cells. We noticed, in the transfected cells, heightened ER stress, activation of the PERK-eIF2 arm of the UPR, induction of autophagy and cell death. When we treated the transfected cells with Tauroursodeoxycholic acid (TUDCA), 4-phenyl butyric acid (PBA), Salubrinal, Trazadone hydrochloride, and Dibenzoylmethane (DBM), we saw reduced the BiP/GRP78 levels, but only PBA and TUDCA could significantly diminish the levels of peIF2 and autophagy expression.
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Molnupiravir (EIDD-2801) inhibits SARS-CoV-2 replication and enhances the efficacy of favipiravir in a Syrian hamster infection model -
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+Since its emergence in Wuhan, China in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide resulting in a global pandemic with >2 million deaths within a year of the emergence of the virus. In the search for small molecule inhibitors of SARS-CoV-2 Molnupiravir (EIDD-2801), an orally bioavailable nucleoside analog that was originally developed as an antiviral against influenza viruses but that exerts also activity against a number of other RNA viruses, including SARS-CoV2 and other coronaviruses. We here report on the effect of EIDD-2801 in a well-established Syrian hamster SARS-CoV-2 infection model. Oral treatment of SARS-CoV-2-infected hamsters with EIDD-2801 for four consecutive days, starting from the day of infection, significantly reduced infectious virus titers and viral RNA loads in the lungs and markedly improved lung histopathology in a dose-dependent manner when assessed at 4 dpi. When onset of treatment with 500 mg/kg/dose was delayed until 24h post-infection, a modest but significant antiviral effect was observed. When suboptimal doses of both favipiravir (300 mg/kg, BID) and EIDD-2801 (150 mg/kg, BID) were combined, a complete reduction (~5 log10) of infectious virus titers was observed in the lungs of most of the combo-treated animals whereas either compound alone resulted in a reduction of respectively 1.2 and 1.3 log10. The potential of EIDD-2801 for the treatment and/or prevention of SARS-CoV-2 alone or in combination with favipiravir deserves further attention.
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Sensitive visualization of SARS-CoV-2 RNA with CoronaFISH -
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+The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The positive-sense single-stranded RNA virus contains a single linear RNA segment that serves as a template for transcription and replication, leading to the synthesis of positive and negative-stranded viral RNA (vRNA) in infected cells. Tools to visualize viral RNA directly in infected cells are critical to analyze its replication cycle, screen for therapeutic molecules or study infections in human tissue. Here, we report the design, validation and initial application of fluorescence in situ hybridization (FISH) probes to visualize positive or negative RNA of SARS-CoV-2 (CoronaFISH). We demonstrate sensitive visualization of vRNA in African green monkey and several human cell lines, in patient samples and human tissue. We further demonstrate the adaptation of CoronaFISH probes to electron microscopy (EM). We provide all required oligonucleotide sequences, source code to design the probes, and a detailed protocol. We hope that CoronaFISH will complement existing techniques for research on SARS-CoV-2 biology and COVID-19 pathophysiology, drug screening and diagnostics.
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A model for pH coupling of the SARS-CoV-2 spike protein open/closed equilibrium. -
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+SARS-CoV-2, causative agent of the COVID-19 pandemic, is thought to release its RNA genome at either the cell surface or within endosomes, the balance being dependent on spike protein stability, and the complement of receptors, co-receptors and proteases. To investigate possible mediators of pH-dependence, pKa calculations have been made on a set of structures for spike protein ectodomain and fragments from SARS-CoV-2 and other coronaviruses. Dominating a heat map of the aggregated predictions, 3 histidine residues in S2 are consistently predicted as destabilising in pre-fusion (all 3) and post-fusion (2 of 3) structures. Other predicted features include the more moderate energetics of surface salt-bridge interactions, and sidechain-mainchain interactions. Two aspartic acid residues in partially buried salt-bridges (D290-R273 and R355-D398) have pKas that are calculated to be elevated and destabilising in more open forms of the spike trimer. These aspartic acids are most stabilised in a tightly closed conformation that has been observed when linoleic acid is bound, and which also affects the interactions of D614. The D614G mutation is known to modulate the balance of closed to open trimer. It is suggested that D398 in particular contributes to a pH-dependence of the open/closed equilibrium, potentially coupled to the effects of linoleic acid binding and D614G mutation, and possibly also A570D mutation. These observations are discussed in the context of SARS-CoV-2 infection, mutagenesis studies, and other human coronaviruses.
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One Year of Evidence on Mental Health Disorders in China during the COVID-19 Crisis - A Systematic Review and Meta-Analysis -
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+ABSTRACT Objective: This paper provides a systematic review and meta-analysis on the prevalence rate of mental health issues of the major population, including general population, general healthcare workers (HCWs), and frontline healthcare workers (HCWs), in China over one year of the COVID-19 crisis. Design: A systematic review and meta-analysis. Data sources: articles in PubMed, Embase, Web of Science, and medRxiv up to November 16, 2020, one year after the first publicly known confirmed COVID-19 case. Eligibility criteria and data analysis: any COVID-19 and mental disorders relevant English studies with frontline/general healthcare workers, general adult population sample, using validated scales. We pooled data using random-effects meta-analyses to estimate the prevalence rates of anxiety, depression, distress, general psychological symptoms (GPS), insomnia, and PTSD and ran meta-regression to tease out the heterogeneity. Results: The meta-analysis includes 131 studies and 171 independent samples. The overall prevalence of anxiety, depression, distress, GPS, insomnia, and PTSD are 11%, 13%, 20%, 13%, 19%, and 20%, respectively. The meta-regression results uncovered several predictors of the prevalence rates, including severity (e.g., above severe vs. above moderate, p<0.01; above moderate vs. above mild, p<0.01) and type of mental issues (e.g., depression vs. anxiety, p=0.04; insomnia vs. anxiety p=0.04), population (frontline HCWs vs. general HCWs, p<0.01), sampling location (Wuhan vs. non-Wuhan, p=0.04), and study quality (p=0.04). Limitations: First, we only focus on China population, which may limit the generalizability of the results. Second, 96.2% studies included in this meta-analysis were cross-sectional. Last, since we only included studies published in English, we expect to have a language bias. Conclusion: Our pooled prevalence rates are significantly different from, yet largely between, the findings of previous meta-analyses, suggesting the results of our larger study are consistent with, yet fine-tune, the findings of the smaller, previous meta-analyses. Hence, this meta-analysis not only provides a significant update on the mental health prevalence rates in COVID-19 but also suggests the need to update meta-analyses continuously to provide more accurate estimates of the prevalence of mental illness during this ongoing health crisis. While prior meta-analyses focused on the prevalence rates of mental health disorders based on one level of severity (i.e., above mild), our findings also suggest a need to examine the prevalence rates at varying levels of severity. The one-year cumulative evidence on sampling locations (Wuhan vs. non-Wuhan) corroborates the typhoon eye effect theory. Our finding that the prevalence rates of distress and insomnia and those of frontline healthcare workers are higher suggest future research and interventions should pay more attention to those mental outcomes and populations. Keywords: systematic review; meta-analysis; COVID-19; mental health; epidemic; general population; healthcare workers; frontline healthcare workers
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+The Australian Government9s COVID-19 vaccine rollout strategy is scheduled to commence in late February 2021 and aims to vaccinate the Australian adult population by the end of October 2021. The task of vaccinating some 20 million people within this timeframe presents considerable logistical challenges. Key to meeting this target is the rate of vaccine delivery: the number of vaccine doses that can be administered per day. In the opening phase, high priority groups will receive the Pfizer/BioNTech vaccine through hospital hubs at an initial rate of 80,000 doses per week. However, pending regulatory approval, the currently announced plan appears to be to distribute the AstraZeneca vaccine to the bulk of the popluation through a combination of general practices and community pharmacies. Here, we run a series of projections to estimate how long it will take to vaccinate the Australian population under different assumptions about the rate of vaccine administration as well as the schedule for second doses and prevalence of vaccine hesitancy. Our analysis highlights the ambitious rate of vaccine administration that will be neccessary to meet the Australian Government completion target of October 2021. A rate of 200,000 doses per day would comfortably meet that target; 80,000 doses a day would see roll-out extended until mid-2022. Speed is of the essence when it comes to vaccine rollout: protecting the population quickly will minimise the risk of sporadic and costly lockdowns lockdowns and the potential for small, local clusters getting out of control and sparking new epidemic waves. The government should gather all its resources to maximise the daily vaccination rate, ideally aiming to ramp up administration to at least 200,000 doses per day as quickly as possible. Quickly achieving and maintaining this pace will likely require dedicated large-scale vaccination sites that are capable of delivering thousands of doses a week in addition to the enthusiastic participation of GP practices and community pharmacies around the country. Lessons on the neccessary logistical planning, including coordination of delivery, ultra-cold-chain storage and staffing, can potentially be learned from Israel, where between 7,000 and 20,000 vaccinations per million population have been delivered daily throughout January.
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Dynamics of SARS-CoV-2 with Waning Immunity in the UK Population -
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+The dynamics of immunity are crucial to understanding the long-term patterns of the SARS-CoV-2 pandemic. Several cases of reinfection with SARS-CoV-2 have been documented 48-142 days after the initial infection and immunity to seasonal circulating coronaviruses is estimated to be shorter than one year. Using an age-structured, deterministic model, we explore potential immunity dynamics using contact data from the UK population. In the scenario where immunity to SARS-CoV-2 lasts an average of three months for non-hospitalised individuals, a year for hospitalised individuals, and the effective reproduction number after lockdown ends is 1.2 (our worst case scenario), we find that the secondary peak occurs in winter 2020 with a daily maximum of 387,000 infectious individuals and 125,000 daily new cases; three-fold greater than in a scenario with permanent immunity. Our models suggests that longitudinal serological surveys to determine if immunity in the population is waning will be most informative when sampling takes place from the end of the lockdown in June until autumn 2020. After this period, the proportion of the population with antibodies to SARS-CoV-2 is expected to increase due to the secondary wave. Overall, our analysis presents considerations for policy makers on the longer term dynamics of SARS-CoV-2 in the UK and suggests that strategies designed to achieve herd immunity may lead to repeated waves of infection as immunity to reinfection is not permanent.
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Study to Evaluate the Safety and Efficacy of a Single Dose of STI-2020 (COVI-AMG™) to Treat COVID-19 - Condition: Covid19 Interventions: Biological: COVI-AMG; Drug: Placebo Sponsor: Sorrento Therapeutics, Inc. Not yet recruiting
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Study to Evaluate a Single Dose of STI-2020 (COVI-AMG™) in Adults With Mild COVID-19 Symptoms - Condition: Covid19 Interventions: Biological: COVI-AMG; Drug: Placebo Sponsor: Sorrento Therapeutics, Inc. Not yet recruiting
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Phase III Study of AZD7442 for Treatment of COVID-19 in Outpatient Adults - Condition: COVID-19 Interventions: Drug: AZD7442; Drug: Placebo Sponsor: AstraZeneca Not yet recruiting
TOCILIZUMAB - An Option for Patients With COVID-19 Associated Cytokine Release Syndrome; A Single Center Experience - Condition: Covid19 Intervention: Drug: Tocilizumab Sponsor: FMH College of Medicine and Dentistry Completed
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Convalescent Plasma in the Treatment of Covid-19 - Condition: Covid19 Interventions: Biological: Convalescent plasma from COVID-19 donors; Biological: Placebo Sponsors: Helsinki University Central Hospital; Finnish Red Cross Recruiting
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A Study to Evaluate the Efficacy and Safety of VB-201 in Patients With COVID-19 - Condition: Severe COVID-19 Interventions: Drug: VB-201 + Standard of care; Drug: Standard of care Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics Recruiting
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Efficacy of Nano-Ivermectin Impregnated Masks in Prevention of Covid-19 Among Healthy Contacts and Medical Staff - Condition: Covid-19 Intervention: Other: ivermectin impregnated mask Sponsor: South Valley University Recruiting
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An Outpatient Clinical Trial Using Ivermectin and Doxycycline in COVID-19 Positive Patients at High Risk to Prevent COVID-19 Related Hospitalization - Condition: Covid19 Interventions: Drug: Ivermectin Tablets; Drug: Doxycycline Tablets; Drug: Placebo Sponsor: Max Health, Subsero Health Recruiting
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COVID-19 Immunologic Antiviral Therapy With Omalizumab - Condition: Covid19 Interventions: Biological: Omalizumab; Other: Placebo Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre Not yet recruiting
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CPI-006 Plus Standard of Care Versus Placebo Plus Standard of Care in Mild to Moderately Symptomatic Hospitalized Covid-19 Patients - Condition: Covid-19 Interventions: Drug: CPI-006 2 mg/kg + SOC; Drug: CPI-006 1 mg/kg + SOC; Drug: Placebo + SOC Sponsor: Corvus Pharmaceuticals, Inc. Recruiting
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Phase IIb Clinical Trial of Recombinant Novel Coronavirus Pneumonia (COVID-19) Vaccine (Sf9 Cells) - Condition: COVID-19 Interventions: Biological: Recombinant COVID-19 vaccine (Sf9 cells); Biological: Placebo Sponsors: Jiangsu Province Centers for Disease Control and Prevention; West China Hospital Not yet recruiting
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Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients - Condition: Covid19 Intervention: Drug: Ivermectin Sponsor: FMH College of Medicine and Dentistry Completed
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Famotidine vs Placebo for the Treatment of Non-Hospitalized Adults With COVID-19 - Condition: Covid-19 Interventions: Drug: Famotidine; Drug: Placebo Sponsors: Northwell Health; Cold Spring Harbor Laboratory Recruiting
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Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19 - Conditions: Severe Acute Respiratory Syndrome Coronavirus 2; COVID-19 Interventions: Drug: SNG001; Drug: Placebo Sponsor: Synairgen Research Ltd. Recruiting
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From PubMed
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In silico Screening of Natural Compounds as Potential Inhibitors of SARS-CoV-2 Main Protease and Spike RBD: Targets for COVID-19 - Historically, plants have been sought after as bio-factories for the production of diverse chemical compounds that offer a multitude of possibilities to cure diseases. To combat the current pandemic coronavirus disease 2019 (COVID-19), plant-based natural compounds are explored for their potential to inhibit the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The present study is aimed at the investigation of antiviral action of several groups of…
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Structural basis for the inhibition of the SARS-CoV-2 main protease by the anti-HCV drug narlaprevir - No abstract
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Potent and Selective Knockdown of Tyrosine Kinase 2 by Antisense Oligonucleotides - Tyrosine kinase 2 (TYK2) is a member of the JAK family of nonreceptor tyrosine kinase, together with JAK1, JAK2, and JAK3. JAKs are important signaling mediators of many proinflammatory cytokines and represent compelling pharmacological targets for autoimmune and inflammatory diseases. Pan-acting small-molecule JAK inhibitors were approved for the treatment of rheumatoid arthritis and ulcerative colitis. However, their limited selectivity among JAK members have led to undesirable side effects,…
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A Neutralization Assay Based on Pseudo-Typed Lentivirus with SARS CoV-2 Spike Protein in ACE2-Expressing CRFK Cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic zoonotic virus that spreads rapidly. In this work, we improve the hitherto existing neutralization assay system to assess SARS-CoV-2 inhibitors using a pseudo-typed lentivirus coated with the SARS-CoV-2 spike protein (LpVspike +) and angiotensin-converting enzyme 2 (ACE2)-transfected cat Crandell-Rees feline kidney (CRFK) cells as the host cell line. Our method was 10-fold more sensitive compared to the typical…
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Mechanisms of Coronavirus Nsp1-Mediated Control of Host and Viral Gene Expression - Many viruses disrupt host gene expression by degrading host mRNAs and/or manipulating translation activities to create a cellular environment favorable for viral replication. Often, virus-induced suppression of host gene expression, including those involved in antiviral responses, contributes to viral pathogenicity. Accordingly, clarifying the mechanisms of virus-induced disruption of host gene expression is important for understanding virus-host cell interactions and virus pathogenesis. Three…
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SARS-CoV-2 entry inhibitors by dual targeting TMPRSS2 and ACE2: An in silico drug repurposing study - The coronavirus disease (COVID-19) is spreading between human populations mainly through nasal droplets. Currently, the vaccines have great hope, but it takes years for testing its efficacy in human. As there is no specific drug treatment available for COVID-19 pandemic, we explored in silico repurposing of drugs with dual inhibition properties by targeting transmembrane serine protease 2 (TMPRSS2) and human angiotensin-converting enzyme 2 (ACE2) from FDA-approved drugs. The TMPRSS2 and ACE2…
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An Urgent Industrial Scheme both for Total Synthesis, and for Pharmaceutical Analytical Analysis of Umifenovir as an Anti-Viral API for Treatment of COVID-19 - CONCLUSION: The most important pharmaceutical analytical methods containing OVI test (mainly ethanol (about 171 ppm) much lower than the limits, by gas chromatography-Flame Ionization Detector (GC-FID) instrument), Assay content (about 99.6% by potentiometric titration), and related purity analysis (by High performance liquid chromatography-Ultraviolet Detector (HPLC-UV)) (about 99.8%) were performed and described to give a more clear industrial scheme.
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Ethical Dilemma: An Unprecedented Strike by Health care Workers in Early February 2020 in Hong Kong - Urging the government to exercise a complete border closure to inhibit the spread of the novel coronavirus from Mainland China, about 8,000 health care workers participated in a 5-day strike in early February 2020 in Hong Kong. Despite gaining 61% support from the public, dissenters criticised that the participants violated professional ethics and abandoned their accountabilities, which led to moral distress. However, the participants were guided by the four fundamental medical principles…
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Complement inhibition initiated recovery of a severe myasthenic crisis with COVID-19 - We report on a patient with refractory Myasthenia gravis with acetylcholine receptor antibodies with two prior myasthenic crises suffering from COVID-19 with rapid evolving weakness and respiratory failure. Respiratory failure developed and prolonged mechanical ventilation was necessary. After plasmapheresis, residual, severe generalized and bulbar weakness persisted. Complement inhibition with eculizumab was, therefore, introduced and lead to rapid recovery. In refractory myasthenic crisis…
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Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study - A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness…
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Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity - Human high-density lipoproteins (HDL) show a broad spectrum of antiviral activity in terms of anti-infection. Although many reports have pointed out a correlation between a lower serum HDL-C and a higher risk of COVID-19 infection and progression, the in vitro antiviral activity of HDL against SARS-CoV-2 has not been reported. HDL functionality, such as antioxidant and anti-infection, can be impaired by oxidation and glycation and a change to pro-inflammatory properties. This study compared the…
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Genome-scale metabolic modeling reveals SARS-CoV-2-induced host metabolic reprogramming and identifies metabolic antiviral targets - Tremendous progress has been made to control the COVID-19 pandemic, including the development and approval of vaccines as well as the drug remdesivir, which inhibits the SARS-CoV-2 virus that causes COVID-19. However, remdesivir confers only mild benefits to a subset of patients, and additional effective therapeutic options are needed. Drug repurposing and drug combinations may represent practical strategies to address these urgent unmet medical needs. Viruses, including coronaviruses, are known…
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Analogue discovery of safer alternatives to HCQ and CQ drugs for SAR-CoV-2 by computational design - COVID-19 outbreak poses a severe health emergency to the global community. Due to availability of limited data, the selection of an effective treatment is a challenge. Hydroxychloroquine (HCQ), a chloroquine (CQ) derivative administered for malaria and autoimmune diseases, has been shown to be effective against both Severe Acute Respiratory Syndrome (SARS-CoV-1) and SARS-CoV-2. Apart from the known adverse effects of these drugs, recently the use of CQ and HCQ as a potential treatment for…
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Repurposing of Tetracyclines for COVID-19 Neurological and Neuropsychiatric Manifestations: A Valid Option to Control SARS-CoV-2-Associated Neuroinflammation? - The recent outbreak of coronavirus disease 2019 (COVID-19) has gained considerable attention worldwide due to its increased potential to spread and infect the general population. COVID-19 primarily targets the human respiratory epithelium but also has neuro-invasive potential. Indeed, neuropsychiatric manifestations, such as fatigue, febrile seizures, psychiatric symptoms, and delirium, are consistently observed in COVID-19. The neurobiological basis of neuropsychiatric COVID-19 symptoms is not…
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SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4 - Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here we have isolated primary SARS-CoV-2 viral strains and studied their interaction with human plasmacytoid predendritic cells (pDCs), a key player in antiviral immunity. We show that pDCs are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in…
A PHARMACEUTICAL COMPOSITION OF NITAZOXANIDE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of a nitazoxanide or its pharmaceutically acceptable salts thereof and an mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the nitazoxanide in the ratio of 0.05% to 66% w/v and the mefloquine in the ratio of 0.05% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of nitazoxanide and mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. - link
METHOD AND APPARATUS FOR ACQUIRING POWER CONSUMPTION IMPACT BASED ON IMPACT OF COVID-19 EPIDEMIC - - link
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A PHARMACEUTICAL COMPOSITION OF ARTESUNATE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of an artesunate or its pharmaceutically acceptable salts thereof and a mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the artesunate in the ratio of 0.25% to 66% w/v and mefloquine in the ratio of 0.25% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of Artesunate and Mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. The present invention also discloses a method to preparing the pharmaceutical composition comprising of Artesunate and Mefloquine. - link
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Zahnbürstenaufsatz, elektrische Versorgungseinheit einer elektrischen Zahnbürste, elektrische Zahnbürste mit einem Zahnbürstenaufsatz, Zahnbürste sowie Testaufsatz für eine elektrische Zahnbürste -
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Zahnbürstenaufsatz für eine elektrische Zahnbürste (20) umfassend einen Koppelabschnitt (2), über den der Zahnbürstenaufsatz (1) mit einer elektrischen Versorgungseinheit (10) der elektrischen Zahnbürste (20) verbindbar ist und einen Bürstenabschnitt (3), der zur Reinigung der Zähne ausgebildete Reinigungsmittel (3.1) aufweist, dadurch gekennzeichnet, dass an dem Zahnbürstenaufsatz (1) eine Sensoreinheit (4) vorgesehen ist, die dazu ausgebildet ist, selektiv das Vorhandensein eines Virus oder eines Antigen im Speichel eines Nutzers des Zahnbürstenaufsatzes (1) durch Messen zumindest eines virusspezifischen Parameters zu bestimmen.
一种医用可佩戴式防护口鼻的微型气幕系统 - 本发明公开了一种医用可佩戴式防护口鼻的微型气幕系统，包括框柱，框柱一侧开凿有气幕送风口和呼吸用送风口，气幕送风口和呼吸用送风口内分别连接有软管一和软管二，框柱内开凿有水平条缝和垂直条缝，水平条缝与垂直条缝均与气幕送风口相连通，框柱靠近水平条缝的一侧贯穿开凿有出风口，出风口内设有滤网，出风口贯穿框柱的一端连接有高效过滤器，滤网与高效过滤器之间连接有吸气泵，框柱靠近出风口的一侧连接有电池和开关。本发明通过提出一种在口腔处应用洁净空气幕阻挡气溶胶传播的可佩戴装置，可以在口腔类相关诊疗过程，保护医生和周围人的健康，避免引起可能引发的呼吸道疾病交叉感染。 - link
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COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS - - link
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Vorrichtung umfassend einen Schutzschirm und einen Filter zum Herausfiltern von Viren aus einem Schall erzeugenden Luftstrom -
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Vorrichtung (10) umfassend einen Schutzschirm (12) und einen Filter (14) zum Herausfiltern von Viren (16) aus einem Schall erzeugenden Luftstrom (18), der von einem Musiker (20) beim Musizieren mit einem Musikinstrument oder beim Singen erzeugt wird, wobei der Schutzschirm (12) zur Verringerung des Risikos einer Infektion mit den Viren (16) dafür vorgesehen ist, wenigstens einen Teil der mit dem Luftstrom transportierten Viren (16) aufzufangen, der Schutzschirm (12) eine erste Seite (22) und eine zweite Seite (24) aufweist, die voneinander abgewandt sind, und der Schutzschirm (12) wenigstens einen sich von der ersten (22) bis zu der zweiten Seite (24) erstreckenden Durchlass (26) aufweist, wobei dieser Durchlass (26) zum Durchströmen mit wenigstens einem Teil des beim Musizieren erzeugten Luftstroms (18) vorgesehen ist und der Filter (14) zum Herausfiltern von Viren (16) aus dem Luftstrom (18) in dem Durchlass (26) des Schutzschirms (12) angeordnet ist.
Examining the Case Against the Filibuster - In a new book, Adam Jentleson blames government failures on more than a century of Southern obstruction in the Senate. - link
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Joe Biden Is Playing It Cool with Benjamin Netanyahu - The Biden Administration’s support for the Abraham Accords is having unintended consequences for Israel’s Prime Minister. - link
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On Climate, Biden’s Administration Needs to Combat Zombie Trumpism Quickly - And Montana’s Yaak Valley is a good place to start. - link
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The Risks of Trump’s Impeachment Trial - Given the importance of condemning Trump’s destructive actions, the message sent by an acquittal may be worse than no trial. - link
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The San Francisco School-Renaming Debate Is Not About History - Somehow, our sport of celebrity has blurred into the real work of society-making. - link
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From Vox
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The Marjorie Taylor Greene committee removal vote, explained -
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+Rep. Marjorie Taylor Greene (R-GA) leaves her office at the US Capitol on February 3. | Tasos Katopodis/Getty Images
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+Eleven House Republicans joined Democrats to take the conspiracy theory-promoting lawmaker off her committee assignments.
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+House Republicans were forced to go on the record Thursday evening about Rep. Marjorie Taylor Greene (R-GA) when the lower chamber voted on partisan lines to remove her from her two committee assignments.
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+The vote comes after days of back-and-forth between party leaders, as Democrats have pushed for consequences forthe first-term representative, who has supported or suggested, in no particular order: the QAnon conspiracy theory; Parkland and 9/11 denial; the killing of Democratic leaders; and the idea that 2018 forest fires were started by a Jewish-controlled space laser.
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+The removal vote — which passed 230-199, with 11 Republicans joining the Democrats — could be a watershed moment for both parties, but particularly the GOP. House Republicans effectively weighed in on the future of their party, and whether it welcomes lawmakers like Greene and the supporters they bring.
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+Eleven Republicans voted YEA
Fitzpatrick Gimenez Jacobs of New York Katko Kim of Calif Kinzinger MALLIOTAKIS Salazar Smith of NJ Upton Diaz-Balart
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+But it also could be a pivotal moment in the House’s institutional politics.
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+Disciplining members is a rare tactic, and practically unheard of for comments made before being elected. During debate, Republicans warned that Democrats were opening a “Pandora’s box” of majority tyranny, while Democrats maintained that Greene’s comments represent a uniquely unacceptable situation.
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+Going forward, both parties could have some control over whether it’s a one-off in Congress’s history or a signal of what’s to come.
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+Republicans are trying to unify two very contentious factions
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+The vote is another battle in the ongoing wrestling between the establishment wing of the Republican Party — represented by Rep. Liz Cheney (R-WY) and Senate Minority Leader Mitch McConnell, who have sought to distance the party from former President Donald Trump and Greene — and the pro-Trump, conspiracy-embracing right flank, which includes QAnon supporters, election deniers, and a significant number of House Republicans.
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+In a closed meeting of House Republicans Tuesday night, Greene privately apologized for how her statements may have hurt fellow Republicans, stating that 9/11 and school shootings did happen and saying she embraced QAnon during a dark period of her life but has since moved forward. In a display of just how embedded she is in the House GOP, she received a standing ovation.
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+Of course, Greene is still fundraising off her controversies — she says she has raised $175,000 — and had yet to address the incidents publicly until speaking on the floor Thursday during debate over the resolution. She expressed “regret” over her posts supporting 9/11 and school shooting denial, but did not mention her previous anti-Semitic and raicst remarks or suggestions that House Speaker Nancy Pelosi should be killed.
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+Greene also blamed tech companies for enforcing “cancel culture” by taking “teeny, tiny pieces of words that I’ve said, that you have said, that any of us, and portray us into something we’re not,” and said the media is “just as guilty as QAnon” in promoting lies.
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+Rep. Jim McGovern (D-MA), the chair of the House Rules Committee, spoke with increasing exasperation as the debate went on, saying he had yet to hear an apology from Greene and expressed shock that such a weak explanation warranted a standing ovation from Republicans.
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+If @SpeakerPelosi was the minority leader, she would pull every identity politics trick in the book to defend her member.
White, Woman, Wife, Mother, Christian, Conservative, Business Owner
These are the reasons they don’t want me on Ed & Labor.
+Now, Republicans must weigh the pressures associated with the vote. On the one hand, establishment leaders have condemned Greene. The Democratic Congressional Campaign Committee has been hammering Republicans over Greene, already releasing ads in vulnerable Republican districts linking some moderates to the controversial representative.
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+On the other hand, Trump still wields enormous influence over the party and its base. He has reportedly embraced Greene, and she has explicitly tied herself to the former president, making a vote against her a potential repudiation of Trump and all he represents.
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+In the middle of it all is McCarthy, who tried to unify his caucus in that closed-door meeting, standing behind Cheney and Greene both. Hehas condemned Greene’s statements but taken no action against her.
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+In a statement condemning Greene’s anti-Semitic theories and embrace of violence, McCarthy picked a scapegoat he is betting his whole caucus can agree on: Democrats. And given that Republicans voted overwhelmingly to unsuccessfully keep Greene on her committees, it’s clear his gamble worked.
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+The institutional future of the House is at stake
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+Democrats say Greene’s comments are so egregious that it warrants taking such historic action, and that if Republicans had stepped up and taken care of it themselves — as both parties have previously done with errant members — the vote would be unnecessary. They are particularly bothered by Republican leadership’s decision to place her on the Education Committee, despite her comments about the Parkland shooting and harassment of survivor David Hogg.
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+But Republicans say Democrats are playing with procedural fire, opening the door to a tit-for-tat escalation where the majority party is free to punish members of the minority with whom they disagree.
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+“I understand that Marjorie’s comments have caused deep wounds to many, and as a result, I offered Majority Leader [Steny] Hoyer a path to lower the temperature and address these concerns,” McCarthy said in a statement. “Instead of coming together to do that, the Democrats are choosing to raise the temperature by taking the unprecedented step to further their partisan power grab regarding the committee assignments of the other party.”
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+McCarthy’s comment is a warning shot to Democrats that if they pursue committee removal, Republicans could dictate minority assignments if they take the majority back in 2022. It also provides cover to House GOP members to say they are voting to support Greene purely to keep Democrats from abusing their power as the majority.
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+Rep. Tom Cole (R-OK) embraced that argument speaking on the floor during debate.
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+“The matter we are faced with is bigger than any one individual member,” he said. “It’s about how we as an institution will continue to function in the future. I fear that if we open this particular Pandora’s box, we will not like what happens next.”
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+Asked whether she’s concerned about the precedent being set with the Marjorie Taylor Greene vote, Pelosi responds:
“No, not at all. If any of our members threatened the safety of other members, we’d be the first ones to take them off of a committee. That’s it.”
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+Both parties would have control over whether that becomes the case. It would be an active choice on the part of both Democrats and Republicans (next time they hold the majority) to target members of the other party.
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+Already, a group of House Republicans sponsored a retaliatory amendment to remove progressive Rep. Ilhan Omar (D-MN) from her committee assignments. The move has no political chance in a Democratic House, but sends a clear, though disingenuous, message about punishing supposed “extremism.” As Vox’s Zack Beauchamp has written, comparing the most left-wing Democrats with Greene draws a false equivalency between embracing socialist policies seen in peer democracies and suggesting a cabal of Jews are creating natural disasters from outer space.
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+Democrats, for their part, say the action is uniquely inspired by the circumstances of a member encouraging violence against another member — a stance McGovern said was “not a radical idea” and only unprecedented in that Greene’s party refused to take action.
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+Theywere committed to imposing consequences on Greene, with some members even advocating for censure or expulsion.
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+“The party of Lincoln is becoming the party of violent conspiracy theories,” McGovern said during debate over the resolution. “And apparently the leaders of the Republican Party in the House, today, are not going to do a damn thing about it.”
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+How did we get here?
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+Thursday’s vote is the culmination of a week of negotiation between McCarthy and Hoyer since the newest batch of Greene scandals came to light.
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+In the fallout of the scandals last week, Democrats, including Pelosi, began speaking out against her — particularly after Republicans named her to the House Committee on Education and Labor.
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+McCarthy called Hoyer with a counteroffer: He would move Greene from the Education Committee to a different committee if Democrats agreed to drop the resolution. Hoyer said no, and the Rules Committee moved forward with the resolution, voting to bring it to the floor.
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+Republican leadership discussed potential committee moves for Greene, but ultimately McCarthy decided to let it go to a vote, effectively signaling he — and the members he leads — would defend Greene’s place in the party.
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+The caucus also voted to keep Cheney in the leadership by a vote of 145-61-1 on a secret ballot, demonstrating the pull both wings of the party exert on members.
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+If Trump’s departure from the White House reignited the GOP civil war, McCarthy has made his position clear: The Republican tent is plenty big enough for his detractors — and for QAnon supporters and conspiracy theorists, too.
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+Correction: The House voted largely on partisan lines — with 11 Republicans joining Democrats — to strip Greene of her committee assignments Thursday evening. The fully partisan vote was earlier in the day to advance the resolution.
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Myanmar’s coup has no heroes -
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+Myanmar citizens living in Thailand protest against Myanmar’s military coup outside Myanmar’s Embassy on February 4, 2021. | Peerapon Boonyakiat/SOPA Images/LightRocket via Getty Images
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+This episode of Worldly discusses what happened in Myanmar and what potentially lies ahead.
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+On Monday, Myanmar’s military launched a coup, detaining the country’s democratically elected civilian leader, Aung San Suu Kyi, along with hundreds of members of her political party.
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+Their actions put an end to Myanmar’s decade-long experiment with quasi-democratic rule, calling the country’s future into question and posing some serious challenges to Biden’s pro-democracy agenda.
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+On this week’s episode of Worldly, Vox’s Zack Beauchamp, Jenn Williams, and Alex Ward discuss why the coup happened, why both sides in this fight are morally compromised, and what the Biden administration and the international community can (and can’t) do in response.
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+As Ward has previously explained, Myanmar’s ruling military junta maintained solid control of the country for decades. Suu Kyi, a prominent advocate for democracy, was placed under house arrest for speaking out, gaining her international fame and support.
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+But during the Obama administration, after years of political and economic pressure from the United States and other nations — including strict economic sanctions — Myanmar’s military began to make some modest moves toward democracy.
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+In 2010, they released Suu Kyi from detention, and in 2015, her National League for Democracy (NLD) party won 77 percent of the seats in parliament in the country’s first free and fair election in 25 years.
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+Since then, Suu Kyi has run the country in her role as “state counsellor” alongside the Myanmarese military, which still retained significant power.
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+Yet Suu Kyi began to push for constitutional reforms that would further restrict the military’s role in governing the country, thereby threatening the military’s grip on power. And in the country’s November 2020 elections, Suu Kyi’s party gained massive support, essentially giving her a mandate to pursue those reforms.
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+So hours before Myanmar’s parliament was set to seat its new members, the military seized control and again placed Suu Kyi under house arrest.
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+But while the military’s actions are reprehensible, Suu Kyi is no angel herself.
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+Once an international darling who was awarded the Nobel Peace Prize for her fight for democracy and emphasis on nonviolence, Suu Kyi fell from grace internationally when she supported the military’s 2017 campaign of genocide against the Rohingya, a Muslim ethnic minority group. She not only refused to condemn the military for its actions, but went as far as to defend them in an international court.
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+That poses a challenge for the Biden administration and the international community because while the US and its partners want to support the pro-democracy movement in the country against the military regime, it’s harder to do now that the leader of that movement is potentially complicit in genocide.
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+The Biden administration has officially labeled the takeover a coup and said it is considering placing economic sanctions on Myanmar’s military. But US allies in the region, particularly Japan and South Korea, are big trading partners with Myanmar and likely won’t support these sanctions, which means imposing them will have less bite.
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+A delicate path lies ahead for the Biden administration. There are things the US can do to help, but the core problems that have plagued Myanmar for decades, including the often-violent repression of its many ethnic and religious minorities, remain.
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+To hear more about what led to Myanmar’s coup and what it means for the country’s future, listen below.
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+And don’t forget to subscribe to Worldly wherever you get your podcasts, including Apple Podcasts, Google Podcasts, Spotify, and Stitcher.
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The Senate vote-a-rama gets Democrats closer to approving Covid-19 relief on their own -
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+Senate Majority Leader Chuck Schumer speaks during a press conference about student debt outside the US Capitol on February 4, 2021, in Washington, DC. | Drew Angerer/Getty Images
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+The Senate is kicking off its budget resolution with a process known as a vote-a-rama.
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+The Senate is in the middle of one of its lengthiest — and most interestingly named — processes: the “vote-a-rama” for a budget resolution.
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+It’s happened a handful of times in the past decade or so; this time, it’s part of Democrats’ bid to either pass President Joe Biden’s $1.9 trillion Covid stimulus plan or push Republicans into a more conciliatory position for a bipartisan plan.
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+As the name suggests, this effort involves lots and lots of back-to-back floor votes, and marks the next major step in advancing a budget reconciliation bill that would enable Democrats to approve their version of Covid-19 relief unilaterally. Typically, most bills require 60 votes to advance in the Senate, but budget bills only require 51. By using budget reconciliation to pass Covid-19 relief, Democrats would be able to move everything from $1,400 stimulus checks to enhanced weekly unemployment insurance payments single-handedly, even if Republicans don’t sign on.
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+Although there’s still the possibility of a bipartisan deal on Covid-19 aid, Democrats have gone ahead and initiated the reconciliation process, since it’s possible GOP lawmakers stand firm and refuse to back an ambitious package.
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+Before Democrats can get to writing this bill, however, both the Senate and the House need to approve a budget resolution, and the vote-a-rama is an opportunity for every senator to introduce amendments to this measure. The resolution effectively serves as an outline for what the final bill could look like.
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+During the vote-a-rama, which began on Thursday afternoon, each amendment gets about 10 minutes of floor consideration, followed by a rapid-fire vote. Like the budget resolution itself, amendments can pass with a simple majority, or 51 votes.
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+Any amendment that’s budget-related can be considered as part of this process. And because of this flexibility, lawmakers have filed amendments that run the gamut from addressing tax policy for remote workers to funding for schools. In one instance, an amendment from Sens. Joe Manchin (D-WV) and Susan Collins (R-ME) would bar “upper-income taxpayers” from receiving stimulus payments.
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+McConnell’s office outlines 5 GOP vote-a-rama priorities, including amendments that would:
— Prohibit stimulus checks to illegal immigrants
— Reduce $$ to states that have an active investigation into nursing homes for underreported deaths
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+Republicans, in particular, are using this opportunity to hold messaging votes: For example, one of their amendments focuses on preventing stimulus checks from going to undocumented immigrants — something that was already the case in previous Covid-19 relief packages. But by holding a vote on this issue, and others, Republicans aim to get their Democratic counterparts on the record about them.
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+Because of how many amendments they involve, vote-a-ramas can take a long time: In 2013, lawmakers were in the Senate until 5 am. And in 2008, the Senate considered a total of 44 amendments. This time, roughly 700 amendments have been filed (though not all will end up getting a vote).
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+Once the protracted vote-a-rama is over, the path to writing the Covid-19 relief bill and moving forward with budget reconciliation is effectively cleared.
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+What’s next
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+After lawmakers work through amendments to the resolution, both chambers need to pass this measure, so that Congress can get started on writing the budget bill. Here’s what comes next in that process:
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+The Senate votes on the amended budget resolution: After amendments have been considered, the Senate will vote to approve the budget resolution, which can pass with 51 votes.
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+The House must approve an identical budget resolution, too: Both chambers of Congress must approve the budget resolution for the process to move forward and for lawmakers to start crafting a budget reconciliation bill. Since Democrats have House and Senate control, the lower chamber is poised to approve the final version that the Senate passes on Saturday.
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+Once both chambers approve the resolution, lawmakers can begin writing the bill: The resolution directs House and Senate committees to write the bill, and to ensure that it includes the provisions of Biden’s Covid-19 package.
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+Congress then votes on the final bill: This final budget bill can pass with just 51 Senate votes as well, giving Democrats the opportunity to pass it unilaterally. Democrats are aiming to approve the legislation ahead of a March 14 deadline, when the current enhanced unemployment benefits are scheduled to expire.
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+The politics of the budget reconciliation process, briefly explained
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+Democrats are starting the budget reconciliation process at the same time that Biden is negotiating with Republicans and Democrats alike on the parameters of his Covid-19 relief package.
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+Republican senators who want to work with Biden have proposed a counteroffer of $600 billion — which is nowhere near what the administration wants.
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+“There’s obviously a big gap between $600 billion and $1.9 trillion,” White House press secretary Jen Psaki told reporters on Monday. “Clearly, [Biden] thinks the package size needs to be closer to what he proposed than smaller.”
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+With reconciliation as a backdrop, the message to Republicans is: You can either negotiate something closer to what we want or we’ll pass it anyway on a party-line vote.
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+Democrats in Congress and the White House say they want bipartisan talks to continue. But many are also wary of negotiations dragging out for months like they did during the Obama years, wasting precious time to stimulate the economy.
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+Working toward a bipartisan deal — or at least trying to — is part of Biden’s nature, but it’s also good politics.By negotiating directly with moderate Republicans, Biden is also trying to keep centrist Democrats like Sens. Joe Manchin (WV) and Kyrsten Sinema (AZ) happy. Helping Senate Majority Leader Chuck Schumer keep his caucus in line may be just as important, if not more so, as finding areas of common ground with Republicans. Democrats are holding on to their Senate control by a single vote; they have no room for error even with a simple majority vote.
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+“Any senator who’s willing to act contrary to their leadership has power,” former Sen. Heidi Heitkamp of North Dakota told Vox.
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+This is the latest time the budget reconciliation process has been used
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+Back in 2017, congressional Republicans were the ones making fast use of the budget reconciliation process.
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+With unified control of the White House and Congress, Republicans used reconciliation twice: once in their unsuccessful attempt to overturn the Affordable Care Act, and once in their successful passage of a $1.5 trillion tax cut bill that slashed the corporate tax rate from 35 percent to 21 percent, among other things.
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+In other words, as much as Republicans are grumbling about Democrats using budget reconciliation now to potentially pass more Covid-19 relief, they’re familiar practitioners themselves.
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+If Democrats ultimately do use reconciliation to pass Biden’s Covid-19 relief plan, it likely won’t be the last time they use it. Senate Majority Leader Chuck Schumer has already floated it as a possible vehicle to pass large portions of Biden’s yet-to-be-released economic recovery plan, which will likely include an infrastructure package, among other things.
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+Still, there will likely be a lot of other items on the new president’s to-do list that can’t be passed with budget reconciliation. For instance, Biden has already introduced an immigration bill as another top priority of his administration. He’ll either have to compromise with Republicans on a number of other issues or Senate Democrats could blow up the filibuster — which is looking unlikely.
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+“If they want to get it moving fast, work with us on a bipartisan solution, and then use your political muscle with reconciliation later on,” Republican Sen. Lisa Murkowski (AK) told Vox recently. “But at least show evidence of the value of working together. If we move toward reconciliation, I wonder what signal that sends to those of us who want to try to advance solutions that might not be 100 percent solutions but are 80 percent solutions.”
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From The Hindu: Sports
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Bio-bubbles are mentally draining, Indian cricketers must get two-week break after IPL: Ravi Shastri - The Indian players have not taken a break since the IPL 2020 in September in the UAE
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Williams withdraws from semifinals in Australian Open tuneup - Serena Williams withdrew from an Australian Open tuneup tournament citing a right shoulder injury on Friday within hours of setting up a semifinal ma
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India vs. England first Test | Bumrah, Ashwin strike as England reach 67/2 at lunch on Day 1 - Skipper Joe Root, playing his 100th Test, was batting on 4 while opener Dominic Sibley was undefeated on 26 (96 balls, 3 fours) going into the lunch break.
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India vs England | Joe Root receives special cap for his 100th Test - The England captain a stylish right-hander, got it from star all-rounder Stokes prior to the start of the Test at the M.A.Chidambaram stadium in Chennai
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India vs England | Root hits ton in 100th Test as visitors end Day 1 on 263/3 - Root’s unbeaten knock was studded with 14 boundaries and a six
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From The Hindu: National News
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Worldview with Suhasini Haidar | The military coup in Myanmar and its repercussions - Diplomatic Affairs Editor Suhasini Haidar takes a deep dive into the happenings at Myanmar, answering key questions about what the future holds for the country and its neighbours, including India.
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Aero components sector to double to ₹ 60,000 cr. by 2024, says Rajnath Singh - Between 2016 and 2019, 138 proposals worth over $37 billion for domestic manufacturing had been approved, he says.
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BJP MLAs protest as Mamata Banerjee tables Budget - Chief Minister presented the last Budget before the Assembly polls
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Seaweed farming project yet to take off - Studies raise doubts regarding feasibility of the industry along Kerala coast
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Nana Patole appointed Maharashtra Congress president - Six working presidents and ten vice presidents also appointed.
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From BBC: Europe
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Russia Navalny trial a ‘low point’ in EU-Russia relations, says Borrell - As the opposition politician returns to court, the EU repeats its call for his release from jail.
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Denmark to build ‘first energy island’ in North Sea - The ambitious and costly artificial island will provide energy for three million households.
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French skiers swerve Covid in cross-country boom - Cross-country replaces downhill skiing in French resorts struggling to survive the pandemic.
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Europe’s Roma: ‘Even dogs can’t live like this’ under Covid - Inhabitants in one of Bulgaria’s largest Roma settlements say they feel abandoned during the pandemic.
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France bomb plot: Iran diplomat Assadollah Assadi sentenced to 20 years - Assadollah Assadi is convicted by a Belgian court of planning an attack on an opposition rally in 2018.
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From Ars Technica
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Rocket Report: SpaceX sets new reuse record, Astra valued at $2.1 billion - “This takes us a step closer to our mission of improving life on Earth from space.” - link
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Lost Alaskan Indigenous fort rediscovered after 200 years - The Tlingit built the Sapling Fort in 1804 to repel a Russian naval attack. - link
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Signs that SARS-CoV-2 is evolving to avoid immune responses - Mutations are changing, but not eliminating, the antibody response to the virus. - link
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Remastered images reveal how far Alan Shepard hit a golf ball on the Moon - 50 years ago, the Apollo 14 astronaut hit a golf ball that traveled roughly 40 yards. - link
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Zoombombing countermeasures are ineffective in the vast majority of cases - Password-protecting meetings is among the most ineffective protections. - link
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From Jokes Subreddit
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I’m in a really bad place right now. -
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+Not mentally, I’ve just found myself in fucking Utah.
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The day after his wife disappeared in a kayaking accident in the Bay Of Fundy, Nova Scotia , a man answered his door to find two grim-faced Mounties. “We know it’s late, sir, but we have some information about your wife,” said one of the Mounties. -
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+“Tell me! Did you find her!?” the husband shouted.
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+The Mounties looked at each other. One said,
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+“We have some bad news, some good news, and some really great news.. Which do you want to hear first?”
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+Fearing the worst, the ashen husband said “Give me the bad news first.”
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+The second Mountie said, “I’m sorry to tell you, sir, but this morning we found your wife’s body in the bay.” “Oh my God!” exclaimed the husband. Swallowing hard, he asked, “What’s the good news?”
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+The Mountie continued, “When we pulled her up, she had 6 twenty-five pound snow crabs and 12 good-size lobsters clinging to her.”
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+Stunned, the husband demanded, “If that’s the good news, what’s the great news???”
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+The Mountie answered, “We’re gonna pull her up again tomorrow.”
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An Irish housewife is at home, being a homemaker, while her husband is away working at the Guinness factory -
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+When she hears a knock on the door.
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+Upon answering the door, she sees it is two of her husband’s friends and co-workers.
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+“Mary,” says the first co-worker, “I’m afraid we have some terrible news. You see, there was an accident at the factory today, and your husband fell into a vat of the Guinness.”
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+“My God!” Exclaims Mary, “will he be alright, how badly is he hurt!?”
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+“Well,” says the co-worker, “the fact is Mary, he didn’t make it, he drowned.”
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+“No!” Sobs Mary. “Please, tell me it was at least a quick death, and painless?”
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+“Well, you see, the thing of it is Mary, he got out three times to pee.”
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There was a very, very unlucky man with a single testicle. -
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+One day, he went on a plane. Unfortunately, a malfunction occurred. The flight crew announced that the plane was going down and one of the passengers had to be thrown out to reduce weight.
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+To determine the victim, passengers drew lots, and the unlucky man was chosen. He refused furiously, saying “No, I lived a miserable life because of my bad luck and I refuse to let it dictate the end of my days!”
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+Passengers drew lots for the second time, he was chosen again. He refused for the second time, with less determination.
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+When the lots were drawn for the third time, his name was chosen once more. He refused again.
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+Finally, when his name appeared again after the fourth ballot, he said:
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+“OK, I agree to jump off the plane on one condition. You have to guess this correctly: What is the total number of testicles of me and the man in front of me?”
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+Passengers looked at each other with slight surprise and a grin on their faces and said “Four, of course!”. The man laughed at them saying “No! You’re wrong, as you see!” while revealing his proud, single testicle to them. Then the other man pulled down his pants…
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