Disease, perceived infectibility and threat reactivity: a COVID-19 study -
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+We investigate whether COVID-19 exposure changes participants’ threat-detection threshold. Sensitivity to threat was measured in a signal detection task among 397 British adults who also reported how much vulnerable they felt to infectious disease. Participants’ data were then matched to the number of confirmed COVID-19 collected from the NHS database. We found that participants who perceive themselves as more likely to catch infectious diseases displayed a higher negativity bias in response to increased COVID-19 cases. In addition, we found a significant effect of education on participants’ punishment responsiveness in response to COVID-19 exposure. A second wave of data collection is planned exactly two weeks after the first one. The goal of this second wave is to replicate the findings and document the impact of increasing COVID-19 cases and deaths on people’s psychology.
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CD47 as a potential biomarker for the early diagnosis of severe COVID-19 -
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+The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. Antiviral interventions are only effective prior to the onset of hyperinflammation. Hence, biomarkers are needed for the early identification and treatment of high-risk patients. Here, we show in a range of model systems and data from post mortem samples that SARS-CoV-2 infection results in increased levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells. Systematic literature searches also indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions which may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, CD47 is a candidate biomarker for severe COVID-19. Further research will have to show whether CD47 is a reliable diagnostic marker for the early identification of COVID-19 patients requiring antiviral therapy.
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A Comparison of Performance for Different SARS-Cov-2 Sequencing Protocols -
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+SARS-Cov-2 genome sequencing has been identified as a fundamental tool for fighting the COVID-19 pandemic. It is used, for example, for identifying new variants of the virus and for elaborating phylogenetic trees that help to trace the spread of the virus. In the present study we provide a comprehensive comparison between the quality of the assemblies obtained from different sequencing protocols. We demonstrate how some protocols actively promoted by different high-level administrations are inefficient and how less-used alternative protocols show a significant increased performance. This increase of performance could lead to cheaper sequencing protocols and therefore to a more convenient escalation of the sequencing efforts around the world.
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Meta-Research: Citation needed? Wikipedia and the COVID-19 pandemic -
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+With the COVID-19 pandemic’s outbreak at the beginning of 2020, millions across the world flocked to Wikipedia to read about the virus. Our study offers an in-depth analysis of the scientific backbone supporting Wikipedia’s COVID-19 articles. Using references as a readout, we asked which sources informed Wikipedia’s growing pool of COVID-19-related articles during the pandemic’s first wave (January-May 2020). We found that coronavirus-related articles referenced trusted media sources and cited high-quality academic research. Moreover, despite a surge in preprints, Wikipedia’s COVID-19 articles had a clear preference for open-access studies published in respected journals and made little use of non-peer-reviewed research uploaded independently to academic servers. Building a timeline of COVID-19 articles on Wikipedia from 2001-2020 revealed a nuanced trade-off between quality and timeliness, with a growth in COVID-19 article creation and citations, from both academic research and popular media. It further revealed how preexisting articles on key topics related to the virus created a framework on Wikipedia for integrating new knowledge. This “scientific infrastructure” helped provide context, and regulated the influx of new information into Wikipedia. Lastly, we constructed a network of DOI-Wikipedia articles, which showed the landscape of pandemic-related knowledge onWikipedia and revealed how citations create a web of scientific knowledge to support coverage of scientific topics like COVID-19 vaccine development. Understanding how scientific research interacts with the digital knowledge-sphere during the pandemic provides insight into how Wikipedia can facilitate access to science. It also sheds light on how Wikipedia successfully fended of disinformation on the COVID-19 and may provide insight into how its unique model may be deployed in other contexts.
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Day-night and seasonal variation of human gene expression across tissues -
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+Circadian and circannual cycles trigger physiological changes whose reflection on human transcriptomes remains largely uncharted. We used the time and season of death of 932 individuals from GTEx to jointly investigate transcriptomic changes associated with those cycles across multiple tissues. For most tissues, we found little overlap between genes changing expression during day-night and among seasons. Although all tissues remodeled their transcriptomes, brain and gonadal tissues exhibited the highest seasonality, whereas those in the thoracic cavity showed stronger day-night regulation. Core clock genes displayed marked day-night differences across multiple tissues, which were largely conserved in baboon and mouse, but adapted to their nocturnal or diurnal habits. Seasonal variation of expression affected multiple pathways and were enriched among genes associated with SARS-CoV-2 infection. Furthermore, they unveiled cytoarchitectural changes in brain subregions. Altogether, our results provide the first combined atlas of how transcriptomes from human tissues adapt to major cycling environmental conditions.
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Structural O-Glycoform Heterogeneity of the SARS-CoV-2 Spike Protein Receptor-Binding Domain Revealed by Native Top-Down Mass Spectrometry -
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+Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes an extensively glycosylated surface spike (S) protein to mediate host cell entry and the S protein glycosylation is strongly implicated in altering viral binding/function and infectivity. However, the structures and relative abundance of the new O-glycans found on the S protein regional-binding domain (S-RBD) remain cryptic because of the challenges in intact glycoform analysis. Here, we report the complete structural characterization of intact O-glycan proteoforms using native top-down mass spectrometry (MS). By combining trapped ion mobility spectrometry (TIMS), which can separate the protein conformers of S-RBD and analyze their gas phase structural variants, with ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS analysis, the O-glycoforms of the S-RBD are comprehensively characterized, so that seven O-glycoforms and their relative molecular abundance are structurally elucidated for the first time. These findings demonstrate that native top-down MS can provide a high-resolution proteoform-resolved mapping of diverse O-glycoforms of the S glycoprotein, which lays a strong molecular foundation to uncover the functional roles of their O-glycans. This proteoform-resolved approach can be applied to reveal the structural O-glycoform heterogeneity of emergent SARS-CoV-2 S-RBD variants, as well as other O-glycoproteins in general.
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In vitro screening of herbal medicinal products for their supportive curing potential in the context of SARS-CoV-2 -
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+Background: Herbal medicinal products have a long-standing history of use in the therapy of common respiratory infections. In the COVID-19 pandemic, they may have the potential for symptom relief in non-severe or moderate disease cases. Here we describe the results derived by in vitro screening of five herbal medicinal products with regard to their potential to i) interfere with the binding of the human Angiotensin-converting enzyme 2 (ACE2) receptor with the SARS-CoV-2 Spike S1 protein, ii) modulate the release of the human defensin HBD1 and cathelicidin LL-37 from human A549 lung cells upon Spike S1 protein stimulation and iii) modulate the release of IFN-{gamma} from activated human peripheral blood mononuclear cells (PBMC). The investigated extracts were: Sinupret extract (SINx), Bronchipret thyme-ivy (BRO TE), Bronchipret thyme-primrose (BRO TP), Imupret (IMU), and Tonsipret (TOP). Methods: The inhibitory effect of the herbal medicinal products on the binding interaction of Spike S1 protein and the human ACE2 receptor was measured by ELISA. The effects on intracellular IFN-{gamma} expression in stimulated human PBMCs were measured by flow cytometry. Regulation on HBD1 and LL-37 expression and secretion was assessed in 25d long-term cultured human lung A549 epithelial cells by RT-PCR and ELISA. Results: IMU and BRO TE concentration-dependently inhibited the interaction between spike protein and the ACE2 Receptor. However, this effect was only observed in the cell-free assay at a concentration range which was later on determined as cytotoxic to human PBMC. SINx, TOP and BRO TP significantly upregulated the intracellular expression of antiviral IFN{gamma} from stimulated PBMC. Co-treatment of A549 cells with IMU or BRO TP together with SARS-CoV-2 spike protein significantly upregulated mRNA expression (IMU) and release (IMU and BRO TP) of HBD1 and LL-37 (BRO TP). Conclusions: The in vitro screening results provide first evidence for an immune activating potential of some of the tested herbal medicinal extracts in the context of SARS-CoV-2. Whether these could be helpful in prevention of SARS-CoV-2 invasion or supportive in recovery from SARS-CoV-2 infection needs deeper understanding of the observations.
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Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell -
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+Established in vitro models for SARS-CoV-2 infection are limited and include cell lines of non-human origin and those engineered to overexpress ACE2, the cognate host cell receptor. We identified human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of ACE2. Infection of H522 cells required the SARS-CoV-2 spike protein, though in contrast to ACE2-dependent models, spike alone was not sufficient for H522 infection. Temporally resolved transcriptomic and proteomic profiling revealed alterations in cell cycle and the antiviral host cell response, including MDA5-dependent activation of type-I interferon signaling. Focused chemical screens point to important roles for clathrin-mediated endocytosis and endosomal cathepsins in SARS-CoV-2 infection of H522 cells. These findings imply the utilization of an alternative SARS-CoV-2 host cell receptor which may impact tropism of SARS-CoV-2 and consequently human disease pathogenesis.
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+As enveloped virus, SARS-CoV-2 membrane protein (M) mediates viral release from cellular membranes, but the molecular mechanisms of SARS-CoV-2 virions release remain poorly understood. Here, we performed RNAi screening and identified the E3 ligase RNF5 which mediates ubiquitination of SARS-CoV-2 M at residue K15 to enhance the interaction of viral envelope (E) with M. M-E complex ensures the uniform size of viral particles for viral maturation and mediates viral release. Moreover, overexpression of M induces complete autophagy which is dependent on RNF5-mediated ubiquitin modification. M inhibits the activity of lysosome protease, and uses autolysosomes for virion release. Consequently, all these results demonstrate that RNF5 mediates ubiquitin modification of SARS-CoV-2 M to stabilize the M-E complex and induce autophagy for virion release.
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Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees. -
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+The emergence of SARS-CoV-2 variants highlighted the need to better understand adaptive immune responses to this virus. It is important to address whether also CD4+ and CD8+ T cell responses are affected, because of the role they play in disease resolution and modulation of COVID-19 disease severity. Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.
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Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains -
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+We examined the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.7 that arose in the United Kingdom and spread globally. Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa B.1.351 variant, than of the infecting variant. The drop in cross-reactivity was more pronounced following B.1.1.7 than parental strain infection, indicating asymmetric heterotypic immunity induced by SARS-CoV-2 variants.
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Differential Dynamic Behavior of Prefusion Spike Proteins of SARS Coronaviruses 1 and 2 -
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+The coronavirus spike protein, which binds to the same human receptor in both SARS-CoV-1 and 2, has been implied to be a potential source of their differential transmissibility. However, the mechanistic details of spike protein binding to its human receptor remain elusive at the molecular level. Here, we have used an extensive set of unbiased and biased microsecond-level all-atom molecular dynamics (MD) simulations of SARS-CoV-1 and 2 spike proteins to determine the differential dynamic behavior of prefusion spike protein structure in the two viruses. Our results indicate that the active form of the SARS-CoV-2 spike protein is more stable than that of SARS-CoV-1 and the energy barrier associated with the activation is higher in SARS-CoV-2. Our results also suggest that not only the receptor binding domain (RBD) but also other domains such as the N-terminal domain (NTD) could play a role in the differential binding behavior of SARS-CoV-1 and 2 spike proteins.
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Trends in Thoracic Impedance and Arrhythmia Burden Among Patients with Implanted Cardiac Defibrillators During the COVID-19 Pandemic -
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+Hospitalizations for acute cardiac conditions have markedly declined during the coronavirus disease 2019 (COVID-19) pandemic, yet the cause of this decline is not clear. Using remote monitoring data of 4,029 patients with implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed changes in markers of cardiac status among these patients and compared thoracic impedance and arrhythmia burden in 2019 and 2020 from January through August. We found no change in several key disease decompensation markers among patients with implanted ICD devices during the first phase of COVID-19 pandemic, suggesting that the decrease in cardiovascular hospitalizations in this period is not reflective of a true population-level improvement in cardiovascular health.
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Physical Activity Patterns Among Patients with Intracardiac Remote Monitoring Devices Before, During, and After COVID-19-related Public Health Restrictions -
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+Nationwide public health restrictions due to the coronavirus disease 2019 (COVID-19) pandemic have disrupted people9s routine physical activities, yet little objective information is available on the extent to which physical activity has changed among patients with pre-existing cardiac diseases. Using remote monitoring data of 9,924 patients with pacemakers and implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed physical activity patterns among these patients in 2019 and 2020 from January through October. We found marked declines in physical activity among patients with implantable cardiac devices during COVID-19-related restrictions and the reduction was consistent across age and sex subgroups. Moreover, physical activity among these vulnerable patients did not return to pre-restrictions levels several months after COVID-19 restrictions were eased. Our findings highlight the need to consider the unintended consequences of mitigation strategies and develop approaches to encourage safe physical activity during the pandemic.
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Risk factors for illness severity among pregnant women with confirmed SARS-CoV-2 infection - Surveillance for Emerging Threats to Mothers and Babies Network, 20 state, local, and territorial health departments, March 29, 2020 -January 8, 2021 -
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+Background: Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with SARS-CoV-2 infection. Methods: Pregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during March 29, 2020-January 8, 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics. Results: Among 5,963 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 30-39 years, Black/Non-Hispanic race/ethnicity, healthcare occupation, pre-pregnancy obesity, chronic lung disease, chronic hypertension, cardiovascular disease, pregestational diabetes mellitus or gestational diabetes. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions. Conclusions: Pregnant women with moderate-to-severe or critical COVID-19 illness were more likely to be older and have underlying medical conditions compared to pregnant women with asymptomatic infection or mild COVID-19 illness. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and inform targeted public health messaging.
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Study to Evaluate a Single Dose of STI-2020 (COVI-AMG™) in Hospitalized Adults With COVID-19 - Condition: Covid19 Interventions: Biological: COVI-AMG; Drug: Placebo Sponsor: Sorrento Therapeutics, Inc. Not yet recruiting
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COVID-19 Antithrombotic Rivaroxaban Evaluation - Condition: COVID-19 Intervention: Drug: Rivaroxaban 10 mg Sponsors: Hospital Alemão Oswaldo Cruz; Bayer; Hospital Israelita Albert Einstein; Hospital do Coracao; Hospital Sirio-Libanes; Hospital Moinhos de Vento; Brazilian Research In Intensive Care Network; Brazilian Clinical Research Institute Recruiting
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The Safety and Efficacy of FB2001 in Healthy Subjects and Patients With COVID-19 Infection - Condition: Covid19 Interventions: Drug: FB2001; Drug: FB2001 Placebo Sponsor: Frontier Biotechnologies Inc. Not yet recruiting
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A Safety and Efficacy Study of Human Monoclonal Antibodies, BRII-196 and BRII-198 for the Treatment of Patients With COVID-19 - Condition: COVID-19 Interventions: Drug: BRII-196 and BRII-198; Drug: Placebo Sponsor: Brii Biosciences, Inc. Not yet recruiting
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Safety & Efficacy of Low Dose Aspirin / Ivermectin Combination Therapy for Treatment of Covid-19 Patients - Condition: Covid19 Intervention: Drug: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1) Sponsors: Makerere University; Ministry of Health, Uganda; Mbarara University of Science and Technology; Joint Clinical Research Center Not yet recruiting
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Protecting Native Families From COVID-19 - Condition: COVID-19 Interventions: Behavioral: Motivational Interviewing; Behavioral: COVID-19 Symptom Monitoring System; Behavioral: Motivational Interviewing and COVID-19 Symptom Monitoring System; Other: Supportive Services Sponsor: Johns Hopkins Bloomberg School of Public Health Not yet recruiting
Safety and Efficacy of Thymic Peptides in the Treatment of Hospitalized COVID-19 Patients in Honduras - Condition: COVID-19 Intervention: Biological: Thymic peptides Sponsors: Universidad Católica de Honduras; Pontificia Universidad Catolica de Chile Recruiting
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Safety, Tolerability, and Immunogenicity of the COVID-19 Vaccine Candidate (VBI-2902a) - Condition: Covid19 Interventions: Biological: VBI-2902a; Biological: Placebo Sponsor: VBI Vaccines Inc. Not yet recruiting
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Safety and Immunogenicity Study in Adults of AZD1222 and rAd26-S Administered as Heterologous Prime Boost Regimen for the Prevention of Coronavirus Disease 2019 (COVID-19) - Condition: Covid19 Interventions: Biological: AZD1222; Biological: rAd26-S Sponsors: R-Pharm; AstraZeneca Not yet recruiting
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Breathing Exercise After COVID-19 Pneumonia - Condition: Covid19 Interventions: Other: Breathing exercise with the phone application; Other: Breathing exercise Sponsor: Tokat Gaziosmanpasa University Not yet recruiting
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Trial Efficacy of Saisei Pharma Dietary Supplements MAF Capsules, 148 mg and M Capsules, 148 mg in Hospitalized COVID-19 Patients - Condition: Covid19 Interventions: Dietary Supplement: MAF capsules 148 mg; Dietary Supplement: M capsules 148 mg; Other: Standard of care Sponsor: Saisei Pharma Active, not recruiting
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(CBDRA60) to Prevent or Reduce Symptoms of COVID-19 - Condition: COVID-19 Interventions: Dietary Supplement: CBDRA60 supplement; Dietary Supplement: Placebo Sponsors: Anewsha Therapeutics Inc.; University of Michigan; Biologics Consulting Not yet recruiting
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Impact of Colchicine and Low-dose Naltrexone on COVID-19 - Condition: Covid19 Interventions: Drug: Colchicine 0.6 mg; Drug: Naltrexone Sponsors: HealthPartners Institute; Park Nicollet Foundation Enrolling by invitation
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The RAPID COVID Study - Application of Point-of-Care COVID-19 Testing - Condition: Covid19 Intervention: Diagnostic Test: Spartan COVID-19 Platform Sponsor: Ottawa Heart Institute Research Corporation Not yet recruiting
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From PubMed
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A comprehensive review of hydroxyurea for beta-haemoglobinopathies: the role revisited during COVID-19 pandemic - CONCLUSION: Hydroxyurea is a well-tolerated oral drug which has been in use for many decades. Through its actions of reversible inhibition of ribonucleoside diphosphate reductase enzyme and fetal haemoglobin induction, it exerts many favourable effects on patients with β-haemoglobinopathies. It is currently approved for the treatment of sickle cell disease and non-transfusion dependent β-thalassaemia. Also, there are various observations to suggest that hydroxyurea is an important adjunct in the…
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Low risk of the TMPRSS2 inhibitor camostat mesylate and its metabolite GBPA to act as perpetrators of drug-drug interactions - Camostat mesylate, a potent inhibitor of the human transmembrane protease, serine 2 (TMPRSS2), is currently under investigation for its effectiveness in COVID-19 patients. For its safe application, the risks of camostat mesylate to induce pharmacokinetic drug-drug interactions with co-administered drugs should be known. We therefore tested in vitro the potential inhibition of important efflux (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP, ABCG2)), and uptake transporters…
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Boceprevir, Calpain Inhibitors II and XII, and GC-376 Have Broad-Spectrum Antiviral Activity against Coronaviruses - As the COVID-19 pandemic continues to unfold, the morbidity and mortality are increasing daily. Effective treatment for SARS-CoV-2 is urgently needed. We recently discovered four SARS-CoV-2 main protease (M^(pro)) inhibitors including boceprevir, calpain inhibitors II and XII, and GC-376 with potent antiviral activity against infectious SARS-CoV-2 in cell culture. In this study, we further characterized the mechanism of action of these four compounds using the SARS-CoV-2 pseudovirus…
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Virus-associated ribozymes and nano carriers against COVID-19 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoo tonic, highly pathogenic virus. The new type of coronavirus with contagious nature spread from Wuhan (China) to the whole world in a very short time and caused the new coronavirus disease (COVID-19). COVID-19 has turned into a global public health crisis due to spreading by close person-to-person contact with high transmission capacity. Thus, research about the treatment of the damages caused by the virus or prevention from…
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Management protocol for Fournier’s gangrene in sanitary regime caused by SARS-CoV-2 pandemic: A case report - CONCLUSION: Early management prevents the resection of the other organs by inhibiting the contiguous spread of infection.
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Possible Antiviral Activity of 5-Aminolevulinic Acid in Feline Infectious Peritonitis Virus (Feline Coronavirus) Infection - Feline infectious peritonitis (FIP) is a life-threatening infectious disease of cats caused by virulent feline coronavirus (FIP virus: FIPV). For the treatment of FIP, several effective antivirals were recently reported, but many of these are not available for practical use. 5-amino levulinic acid (5-ALA) is a low-molecular-weight amino acid synthesized in plant and animal cells. 5-ALA can be synthesized in a large amount, and it is widely applied in the medical and agricultural fields. We…
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Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19 - The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support…
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Modalities and Mechanisms of Treatment for Coronavirus Disease 2019 - Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly throughout the world. Although COVID-19 has a relatively low case severity rate compared to SARS and Middle East Respiratory syndrome it is a major public concern because of its rapid spread and devastating impact on the global economy. Scientists and clinicians are urgently trying to identify drugs to combat the virus with hundreds of clinical trials…
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Inhibition of ACE2 Expression by Ascorbic Acid Alone and its Combinations with Other Natural Compounds - CONCLUSION: Our study provides valuable experimental confirmation of the efficacy of micronutrients in controlling ACE2 expression-the coronavirus cellular “entry” point. It further validates the importance of nutrient interactions in various aspects of cellular metabolism and in considering potential therapeutic applications of nutrient-based approaches. The study shows that ascorbic acid and its combination with some natural compounds could be included in developing preventive and therapeutic…
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Exposure of human intestinal epithelial cells and primary human hepatocytes to trypsin-like serine protease inhibitors with potential antiviral effect - Human intestinal epithelial cell line-6 (HIEC-6) cells and primary human hepatocytes (PHHs) were treated with 3-amidinophenylalanine-derived inhibitors of trypsin-like serine proteases for 24 hours. It was proven that treatment with MI-1900 and MI-1907 was tolerated up to 50 μM in HIEC-6. These inhibitors did not cause elevations in extracellular H(2)O(2) levels and in the concentrations of interleukin (IL)-6 and IL-8 and did not alter occludin distribution in HIEC-6. It was also found that…
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Ginkgolic acid and anacardic acid are specific covalent inhibitors of SARS-CoV-2 cysteine proteases - CONCLUSIONS: Our finding provides two novel natural products as promising SARS-CoV-2 antivirals.
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Mechanisms of COVID-19 Entry into the Cell: Potential Therapeutic Approaches Based on Virus Entry Inhibition in COVID-19 Patients with Underlying Diseases - The Coronavirus disease 2019 (COVID-19) virus spread from Wuhan, China, in 2019 and is spreading rapidly around the world. COVID-19 victims are almost associated with cardiovascular disease, high blood pressure, diabetes, and other underlying diseases. Concerning the high prevalence of these disorders, widespread mortality threatens global society, and its fatality rate may increase with increasing COVID-19 prevalence in countries with older populations. Therefore, evaluating patients’ clinical…
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A new class of alpha-ketoamide derivatives with potent anticancer and anti-SARS-CoV-2 activities - Inhibitors of the proteasome have been extensively studied for their applications in the treatment of human diseases such as hematologic malignancies, autoimmune disorders, and viral infections. Many of the proteasome inhibitors reported in the literature target the non-primed site of proteasome’s substrate binding pocket. In this study, we designed, synthesized and characterized a series of novel α-keto phenylamide derivatives aimed at both the primed and non-primed sites of the proteasome. In…
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Glucosylceramide synthase inhibitors prevent replication of SARS-CoV-2 and Influenza virus - The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health. Vaccines are ideal solutions to prevent infection, but treatments are also needed for those who have contracted the virus to limit negative outcomes, when vaccines are not applicable. Viruses must cross host cell membranes during their lifecycle, creating a dependency on processes involving membrane dynamics. Thus, in this study we examined whether the…
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Platelet-Activating Immune Complexes Identified in Critically Ill COVID-19 Patients Suspected of Heparin-Induced Thrombocytopenia - CONCLUSIONS: Our study identifies platelet-activating ICs as a novel mechanism that contributes to critically ill COVID-19.
Compositions and methods for detecting SARS-CoV-2 spike protein - - link
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一种3-羟基丁酰化修饰蛋白质药物及其制备方法和应用 - 本发明涉及医药技术领域，公开了一种3‑羟基丁酰化修饰蛋白质药物（例如抗体）及其制备方法和应用，特别是一种3‑羟基丁酰化修饰抗体及其制备方法和应用。发明人经过大量实验发现，3‑羟基丁酸及其类似物修饰蛋白质药物（例如抗体）后，可以显著提高蛋白质药物的热稳定性、对蛋白酶水解的抗性，降低蛋白质药物的等电点，并显著延长其在受试者体内的半衰期，进而提高其药效。修饰后所得蛋白质药物在科研和临床方面具有广阔的应用前景和较高的商业价值。 - link
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新冠病毒重组融合蛋白、其制备方法和应用 - 本发明提供一种新冠病毒重组融合蛋白、其制备方法和应用。本发明通过对新冠病毒S和N重组融合蛋白的基因序列进行设计，选择最优的片段进行整合，再通过人源HEK293细胞系统重组表达融合蛋白，经过纯化后对融合蛋白的分子量、纯度进行检测，最后利用融合蛋白制成新冠病毒抗体胶体金检测试纸条/试剂盒。与单独使用S蛋白或N蛋白制备的胶体金检测试纸条相比，该重组融合蛋白制备的胶体金检测试纸条具有更高的灵敏度和更低的漏检率。此外，本发明提供的新冠病毒重组融合蛋白可广泛应用于不同平台技术的新冠抗体检测试剂盒开发，如胶体金、荧光免疫层析、化学发光和酶联免疫等。 - link
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稳定的冠状病毒重组蛋白二聚体及其表达载体 - 本发明公开了稳定的冠状病毒重组蛋白二聚体及其表达载体，冠状病毒重组蛋白，由冠状病毒S蛋白S‑RBD、冠状病毒N蛋白的CTD区N‑CTD和将二者偶联的连接子构成。本发明一些实例的冠状病毒重组蛋白，可以形成并维持稳定的二聚体结构，避免单体S‑RBD降解，有利于提高冠状病毒重组蛋白的免疫原性，有望用于制备检测试剂原料、疫苗、抗体、预防或治疗性药物。本发明一些实例的冠状病毒重组蛋白二聚体，具有很好的免疫原性。在疫苗开发领域具有广阔的应用前景。本发明一些实例的表达载体，易于表达冠状病毒重组蛋白二聚体且表达量高。 - link
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SELF-CLEANING AND GERM-KILLING REVOLVING PUBLIC TOILET FOR COVID 19 - - link
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一种新冠病毒S1蛋白的灌流生产系统及方法 - 本发明涉及细胞生物学技术领域，提供了一种新冠病毒S1蛋白的灌流生产系统及方法，包括：细胞反应器，用于培养表达S1蛋白的细胞株；灌流系统，包括过滤装置、出液管、回液管和第一循环泵，所述过滤装置的主体内设有孔径为0.1‑0.2μm的中空纤维柱，用于过滤透出液，截留细胞培养液中的S1蛋白；所述出液管的两端分别与所述细胞反应器和所述中空纤维柱的下端相连通；所述回液管的两端分别与所述细胞反应器和所述中空纤维柱的上端相连通；所述第一循环泵设置于所述出液管与所述中空纤维柱相连的管路中。本发明系统投入成本低且S1蛋白产量高。 - link
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检测新冠病毒的方法及试剂盒 - 本发明公开了一种检测新冠病毒的方法及试剂盒。其中，该方法包括以下步骤：1）采集样本；2）采用核酸释放剂提取核酸；3）采用LAMP扩增进行检测，其中，核酸释放剂包括：热敏蛋白酶1000U/L~10000U/L、Tris‑HCl 5~50 mmol/L、曲拉通X‑100体积百分比0.05%0.5%和金属离子螯合剂0.10.5mmol/L，其余为无菌水，热敏蛋白酶为≥55℃加热5~10分钟会完全失活的蛋白酶。应用本发明的检测新冠病毒的方法及试剂盒，检测新冠病毒，检测周期短，操作简单方便，检测结果通俗易懂，检测特异性高，检测成本低。 - link
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一种新型冠状病毒拉曼光谱数据中心的构建方法 - 本发明公开了一种新型冠状病毒拉曼光谱数据中心的构建方法，该方法包括以下步骤：S1.构建新冠病毒结构蛋白拉曼光谱数据库；S2.构建新冠病毒核酸拉曼光谱数据库；S3.构建新冠病毒颗粒拉曼光谱数据库；S4.构建新冠病毒临床检测样本拉曼光谱数据库；将各新型冠状病毒拉曼光谱数据库存入新型冠状病毒拉曼光谱检测服务器构成新型冠状病毒拉曼光谱数据中心。本发明有效建立了一套完整的新型冠状病毒拉曼光谱数据库，为新冠病毒拉曼检测技术提供可靠的标准数据支撑，有效提高检测结果的准确性及置信度。 - link
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+Daily-Dose
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The Good, the Bad, and the Embarrassing in America’s COVID-19 Response - Were Americans too unruly, or did elected officials expect too little of them? - link
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Why Won’t Amnesty International Call Alexey Navalny a Prisoner of Conscience? - The Russian regime has used both its vast media infrastructure and its judicial system to vilify its opponents. - link
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Inside Xinjiang’s Prison State - Survivors detail the scope of China’s campaign of persecution against ethnic and religious minorities. - link
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When the Kids Started Getting Sick - After pressure from families, Pennsylvania has launched studies into whether fracking can be linked to local illnesses. - link
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A Year in America’s First COVID Epicenter - Twelve months after Seattle suffered the first reported coronavirus death in the U.S., city leaders reflect on what has worked—and what remains agonizingly broken. - link
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From Vox
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One Good Thing: The brutal beauty of Veneno -
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+Daniela Santiago in Veneno. | Courtesy of HBO Max
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+I need everyone to watch Veneno, a stunning HBO Max series about storytelling and survival.
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+Sometimes, when we’re lucky, we get a TV show like Veneno — the kind of show that jolts you awake and makes you pay attention. The kind that makes you think about the countless ways we tell stories and all the possibilities we haven’t yet staked out. The kind that gives you the power to see the world differently and makes your senses tingle. The kind that makes you want to talk about it with anyone and everyone.
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+This kind of TV show, unfortunately, doesn’t come around often enough. And that’s why, I suppose, I’m writing about Veneno, an eight-episode, one-season HBO Max original series that I fully believe is the best television show of the last year.
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+Veneno, in practical use, is the Spanish word for venom. But it’s also the nickname of one Cristina Ortiz Rodríguez or “La Veneno,” a real-life, Spanish transgender singer and celebrity who rose to prominence in the mid-’90s after appearing on one of Spain’s popular late-night TV shows. Veneno is about her life, and all its joys and complications.
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+“Sultan, courtesan, Indian-like Pocahontas, but with a shark,” she tells a reporter when she’s asked to describe herself in the first episode (the show, which is in Spanish, is available to stream with English subtitles or English dubbing). “The shark … It’s between my legs. What else would the shark be?”
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+What Veneno makes clear is that at the time, sex work was one of the only acceptable professions for trans women. So on the margins of society, Cristina created her own life where she could be La Veneno and write the rules of her own existence. Within that existence, she can be whoever she wants to be — a sultan, a courtesan, Pocahontas — in ways that broader society would never accept (and maybe she didn’t always have the courage for).
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+Fantasy and beauty are redemptive; they are power.
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+ Courtesy of HBO Max
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+Daniela Santiago in Veneno.
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+Veneno is very much about Cristina as it chronicles her childhood, the trauma she endured, how she learned to overcome said trauma, and how she built a persona and wielded a sense of lethality to survive. But the series also examines her effect on other people: what this uncontrollable woman meant to the queer community, particularly transgender men and women, who watched her fight so many of their own internal and external battles in the public eye.
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+That perspective materializes through the eyes of a teenage Valeria Vegas, a college student who seeks to learn what happened to the La Veneno she saw on television as a kid. She catches up with La Veneno, whose glamour and glitz have given way to older age and a purple bathrobe she wears in the daytime. Valeria is not fully out herself when she meets her hero, and the show explores their parallel journeys about finding acceptance and what we learn from our chosen families.
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+Through flashbacks and shifts to present day, the two relive La Veneno’s life: the regrets, the joys, the excitement, the nemeses, the embarrassments, the volatility, and maybe — finally — the peace, because Vegas wants to write La Veneno’s biography.
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+That biography —¡Digo! Ni puta ni santa. Las memorias de La Veneno (Not a Whore, Not a Saint: The Memories of La Veneno), which the real-life Vegas published in 2016 — serves as source material for the series. Vegas is credited as a writer on the show’s eight episodes and some of La Veneno’s real-life friends even play themselves.
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+Perhaps fittingly, the larger-than-life adult Cristina is played by three outstanding actresses, each one covering a different time period in her life. Jedet Sánchez, Daniela Santiago, and Isabel Torres play three largely different roles (Santiago gets to embody La Veneno at her splashiest, right when she becomes a star), but each one imbues her with dignity and humanity. Torres, in particular, will take your breath away as an older Cristina, wistfully looking back at the life she lived but never letting it slip into unmitigated sentimentality.
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+In many ways, Veneno is already groundbreaking just by its existence because of the way it confronts an utter lack of representation in the status quo. Shows about the trans experience and primarily about trans characters are few and far between (trans actors play the trans people in Cristina’s story). We’re still at a point where cisgender actors are stumbling through apologies for considering and taking transgender roles in movies and on TV. Sex work is still a topic the media struggles to get right. That Veneno is a breakthrough for television is both a compliment and an ugly truth about the progress the medium still needs to make.
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+But the revelations in Veneno don’t stop at representation.
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+Thematically, Veneno has a lot in common with the recently released It’s a Sinand the earlier FX series Pose (the latter of which accounts for the bulk of trans representation on TV). Emotionally, I’d also compare it to director Pedro Almodovar’s movies. One of my friends said it was like Tim Burton’s Big Fish, if Big Fish was about Paris Is Burning and directed by Almodovar — a perfect description, provided you’re familiar with all those references.
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+And yet, Veneno is quite simply its own beautiful thing.
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+Creators Javier Ambrossi and Javier Calvo have found a way to tell a story that so specifically nails the complexities of queer identity and insecurity in a way that feels so familiar to people who have lived that experience. It’s evident in moments as slight as Valeria’s body language, which tightens when she’s around her family, contrasted with the way she unspools when she’s in Cristina’s apartment. But it’s also present in scenes that are weightier and more honest, like the ones that depict the destructive ways Cristina copes with grief.
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+Their magic is finding a way to portray these difficult emotions without compromising the depth of Cristina’s lived experience.
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+The series is never cruel to Cristina, but it doesn’t paint her as infallible either. Veneno realizes that Cristina, like all of us, are architects of our own lives. The way each of us sees the world is a result of how we discern between reality and fantasy.
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+For queer people especially, that fantasy becomes more important when faced with a reality that doesn’t have space for you. Perhaps, like Cristina, you embrace the strength of storytelling to become the courtesan, the sultan, or the shark and find your own power — to invent your own legends about having affairs with princes, to will yourself to believe in magic and happily ever afters, like living for eternity on a Grecian island.
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+Ambrossi and Calvo acknowledge Cristina’s fantasies as such, playing with magical realism one moment and flanking it with the starkness of reality the next. The disconnect between our actuality and our dreams is purposely harsh, and maybe even painful. But at no moment do they ever deny how important fantasy is to La Veneno’s existence, and how understanding it is vital to understanding our own.
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+Veneno is streaming HBO Max. For more recommendations from the world of culture, check out the One Good Thing archives.
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Why Joe Biden’s pro-union message is so significant -
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+Demonstrators hold signs during a Retail, Wholesale and Department Store Union protest near an Amazon warehouse in Bessemer, Alabama. | Elijah Nouvelage/Bloomberg/Getty Images
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+Some labor historians think Biden’s rhetoric on unionizing is stronger than FDR’s.
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+On Sunday, President Joe Biden did something not heard from a president of the United States in some time: He offered a full-throated endorsement of a worker’s right to collectively bargain.
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+The White House released a video statement of Biden referencing an ongoing vote in Alabama to decide whether Amazon workers at a Bessemer, Alabama, warehouse will unionize. The Bessemer workers are in the middle of a seven-week vote that began in early February and will end in late March. It’s the first time since 2014 that Amazon workers in America will decide whether or not they want representation from the Retail, Wholesale and Department Store Union.
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+“Workers in Alabama — and all across America — are voting on whether to organize a union in their workplace,” Biden said in the video. “It’s a vitally important choice — one that should be made without intimidation or threats by employers.”
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+Workers in Alabama – and all across America – are voting on whether to organize a union in their workplace. It’s a vitally important choice – one that should be made without intimidation or threats by employers.
+Biden’s words and their timing could have a big impact.
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+“It’s basically unprecedented in American history,” Erik Loomis, a history professor at the University of Rhode Island who studies labor rights, told Vox. “Even FDR did not really intervene at the moment of a union election with a direct statement for a particular set of workers.”
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+Biden has promised to be a friend to labor
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+Biden, who received the backing of several prominent labor unions during the campaign,came into office promising to be a pro-union president. This video is a huge boost not only for the Alabama unionization efforts, but for many more workers around the country who may be considering forming a union. If the Bessemer employees unionize, it could push a wave of organizing activity at other Amazon warehouses around the country.
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+What Biden said about workers’ right to form a union was important. But even more important is what he said about what employers cannot do when employees are deciding whether or not to unionize. Alabama is a right-to-work state, meaning employees don’t have to pay dues in a union — which makes it harder for unions to survive.
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+“There should be no intimidation, no coercion, no threats, no anti-union propaganda,” Biden said in the video. “No supervisor should confront employees about their union preferences. It’s not up to me to decide whether anyone should join a union. But let me be even more clear: It’s not up to an employer to decide that either. The choice to join a union is up to the workers — full stop.”
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+Labor history expert Nelson Lichtenstein of the University of California, Santa Barbara tweeted about Biden’s video, “This is new, nothing like it before. Puts Obama to shame.”
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+As the Washington Post and other outlets have reported, Amazon has been actively discouraging the unionization push in Bessemer, putting anti-union flyers in warehouse bathroom stalls and texting employees telling them to vote against forming the union. Amazon didn’t return Vox’s request for comment on Biden’s statement.
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+The next four years of Biden’s administration could be a watershed moment for organized labor in the United States. The president’s early rhetoric and actions mark a big departure from his Republican predecessor President Donald Trump and from Democratic President Barack Obama, who Biden worked alongside as vice president.
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+“We never met with President Obama in the Oval Office in eight years,” North America’s Building Trades Unions President Sean McGarvey told Vox in a recent interview, noting he and other labor leaders met with Biden within the first 30 days of his presidency. “Never has the word ‘union’ flowed off a political leader’s tongue so easily as it has with President Biden.”
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+Coming off a year of the Covid-19 pandemic and resulting economic crisis could also give Biden an opportunity to make the case for increasing the number of unionized jobs, since unions helped protect people’s jobs during the coronavirus recession in 2020. As Vox’s Emily Stewart and Rani Molla wrote:
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+Even though the total number of jobs represented by a union went down by 444,000 in 2020, union jobs made up a larger share of total jobs, 12.1 percent, up half a percentage point from 2019. That’s because, thanks to union protections, people with union jobs were more likely than non-union workers to keep their jobs.
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+Of course, union leaders are still looking to see what concrete action Biden and his administration take on labor issues, including whether they’re able to successfully pass a pro-union bill, the PRO Act, or able to enforce existing labor laws to investigate corporations trying to discourage unionization of their workers.
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+Unions “go by what [presidents] do, not what they say,” McGarvey told Vox.
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+Why Biden’s words matter
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+On Monday, White House press secretary Jen Psaki clarified that Biden was not weighing in specifically on the Amazon union vote (the president did not mention Amazon by name in the video).
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+“We don’t comment on specific cases where it’s before the NLRB or could be before the NLRB, so we aren’t going to weigh in specifically on Amazon. But broadly he believes workers should have the right to organize; hence, he conveyed that in the video.” Still, Biden went out of his way to mention Alabama, where it’s hard to escape the news-making unionization effort in Bessemer.
+
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+Faiz Shakir, the co-founder of progressive media outlet More Perfect Union, told Vox that he had been in contact with White House chief of staff Ron Klain ahead of Biden releasing the video, encouraging the president to come out in favor of the Bessemer unionization push.
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+“It means a lot that Joe Biden did this,” Shakir told Vox. “They were from the jump appreciative of the idea.”
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+Labor historians and activists told Vox that the substance of Biden’s speech and the timing of it, in the middle of the Bessemer vote, are extremely significant. In a series of tweets, Lichtenstein compared Biden to President Franklin Roosevelt, under whose presidency unions flourished due to Roosevelt’s progressive New Deal policies and mass mobilization during WWII.
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+“Biden’s attack on employer intimidation of workers seeking to join a union is something new for a president since [the 19]30s,” Lichtenstein tweeted, adding Biden’s Department of Justice and National Labor Relations Board need to follow through.
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+Loomis, the history professor, told Vox that there’s added significance because unions had far more political power back in the 1930s and 1940s than they currently do. In 1953, 35.7 percent of private-sector workers belonged to unions, according to a 2016 American Journal of Public Health article. By 2020, that number dropped to 6.3 percent, according to the Bureau of Labor Statistics. Public-sector workers in unions are over five times that number, around 34.8 percent.
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+In other words, private-sector unions had more political power back in the 1940s and 1950s, meaning that both Democrat and Republican presidents had to work with them and pay lip service if they wanted to win over union voters.
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+Certainly, organized labor is still a sought-after bloc within Democratic politics, but its relatively low numbers in the private sector show that Biden is responding to a push from the party’s base, rather than a demand from an individual union, Loomis argued.
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+“By Biden making this statement, he’s responding to an overall feeling in the Democratic party for economic justice,” Loomis said. “It’s even beyond the union, it’s simply that growing demand you’re seeing in the Democratic base for a raised minimum wage.”
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+But Shakir, who served as campaign manager for Sen. Bernie Sanders’s 2020 bid for president, says there are a lot of innate similarities between Biden and Sanders on labor issues.
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+“[Biden] campaigned as a pro-union candidate, and I remember many stops along the way in which he and Bernie were often aligned as they spoke to these AFL-CIO and Teamster gatherings,” Shakir told Vox. “There’s a lot of ideological camaraderie.”
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How Biden’s best-laid plans for Iran and Saudi Arabia failed in his first month -
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+President Joe Biden makes an address on February 27. | Samuel Corum-Pool/Getty Images
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+President Biden hasn’t handled Iran and Saudi Arabia like candidate Biden planned.
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+President Joe Biden’s first month handling Iran and Saudi Arabia shows the new administration has succumbed to a classic problem: Initial plans and promises made during a campaign rarely survive once you’re actually governing.
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+As the Democratic candidate, Biden promised a swift return to the Iran nuclear deal. He then aimed to leverage that negotiation to curb other aspects of Tehran’s aggressive behavior — like its growing ballistic missile program — in follow-on chats.
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+And on the campaign trail, Biden called Saudi Arabia a “pariah” state, vowing to make it “pay the price” for human rights violations, including the grisly 2018 murder of dissident, US resident, and columnist Jamal Khashoggi.
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+Though he released an unclassified intelligence report on Friday directly blaming Saudi Arabia’s Crown Prince Mohammed bin Salman for the killing, Biden declined to punish the nation’s de facto ruler outright. Instead of authorizing sanctions, a travel ban, or an asset freeze, the president created the “Khashoggi ban,” which imposes visa restrictions on people who try to silence dissidents abroad. It’s unclear if that includes heads of state, however.
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+That action — combined with the end of US support for Saudi offensive operations in Yemen and a freeze on weapons sales — was meant to “recalibrate,” not “rupture” US-Saudi relations, Biden administration officials say. A major consideration was that MBS, as the crown prince is known, may soon officially run the country, so targeting him personally could doom future relations between Washington and Riyadh.
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+“Our relationship with Saudi Arabia is important,” State Department spokesperson Ned Price told reporters on Monday.
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+On these key foreign policy areas, President Biden therefore hasn’t governed like candidate Biden said he would. That’s invited some criticism of his first month in charge and concern that his choices could leave allies and activists dissatisfied.
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+“They are trying to thread the needle between competing interests,” said Seth Binder, an advocacy officer at the Project on Middle East Democracy. “Trying to please a broad array of interested parties is likely going to end up frustrating many of them.”
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+Biden’s situation is by no means new. Every president has offered a number of foreign policy plans while running for office only to back off them once they’re in charge. Former President Donald Trump, for example, promised to end America’s wars in the Middle East, but after four years, troops remained in Syria, Iraq, and Afghanistan, partly over security concerns.
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+The new administration, then, is just the latest victim of circumstances not aligning with their initial views of events. Now, it has begun to alter its approach, and may need to do so further.
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+“This has been the education of Team Biden,” said Kirsten Fontenrose, who oversaw Gulf issues on Trump’s National Security Council. “Once you come in and everything’s new, you need to scramble a bit and adjust.”
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+Biden hoped for a smooth reentry into the Iran deal. He didn’t get that.
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+In a July 2019 speech, Biden was clear about what he wanted to achieve with Iran once he became president.
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+“If Tehran returns to compliance with the deal, I would rejoin the agreement and work with our allies to strengthen and extend it, while more effectively pushing back against Iran’s other destabilizing activities,” he told a crowd at City University in New York. Those activities, among other things, included its missile program and support for proxies and terrorist groups.
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+In office, Biden’s team continued holding that line: For the US to reenter the agreement, Iran needed to first come back into compliance with the pact’s limitations on its nuclear development. Simply put, Tehran would have to reduce its levels of uranium enrichment to the limits specified in the Iran deal before America would lift any sanctions on the country.
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+Iran, however, showed less willingness to engage in talks. Tehran said the US had to lift sanctions before it would discuss America’s reentry into the pact. And likely in an effort to increase pressure on the US, Iran-aligned proxies fired rockets at anti-ISIS coalition forces outside Erbil, Iraq — killing a Filipino contractor and injuring US troops — and near the US Embassy in Baghdad.
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+After days of “considering” sitting down with the US in an EU-brokered negotiation, Iran on Sunday rejected that plan. The “time isn’t ripe for the proposed informal meeting,” tweeted Saeed Khatibzadeh, the spokesperson for Iran’s Foreign Ministry.
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+Considering US/E3 positions & actions, time isn’t ripe for the proposed informal meeting.
Remember: Trump failed to meet because of his ill-advised ‘Max Failure’. With sanctions in place, same still applies. Censuring is NOT diplomacy. It doesn’t work with Iran.#CommitActMeet
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+This is surely not how Biden’s team thought the process would go. “Iran, which should be the beneficiary of his policy, is kicking Biden in the face,” said Fontenrose, who’s now at the Atlantic Council.
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+While most experts believe Washington and Tehran will eventually get back into the deal, what the new administration has learned is that its best-laid plans need retooling.
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+“The clear strategy that Biden presented during the campaign has not quite translated into this first month,” said Kaleigh Thomas, an Iran expert at the Center for a New American Security in Washington, DC. “We’ve lost the opportunity for a refresh the Biden team was looking to leverage.”
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+Candidate Biden promised to punish top Saudi leaders. He didn’t punish MBS.
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+In a November 2019 Democratic debate, MSNBC’s Andrea Mitchell asked then-candidate Biden if he would reprimand senior Saudi leaders over the Khashoggi murder. His response was unequivocal.
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+“Yes,” he said. “Khashoggi was, in fact, murdered and dismembered, and I believe on the order of the crown prince. And I would make it very clear we were not going to, in fact, sell more weapons to them. We were going to, in fact, make them pay the price and make them, in fact, the pariah that they are. There is very little social redeeming value in the present government in Saudi Arabia.”
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+But on Friday, Biden didn’t follow through on his promise. MBS escaped direct punishment, even though the intelligence report the administration released directly implicated him as the orchestrator behind Khashoggi’s murder.
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+The president and his team seem content with what they’ve already done to “recalibrate” the US-Saudi relationship, including curbing MBS’s access to Biden — he must now interact with Defense Secretary Lloyd Austin, his direct counterpart — and freezing billions in weapons sales to the country. Further, the “Khashoggi ban” could deter foreign leaders from attacking dissidents abroad.
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+Some say the administration’s actions will still be read as a severe reprimand for leaders in Riyadh. “Saudi Arabia is being normalized inside the US,” instead of being seen as a country that won’t be reprimanded for its internal politics save for religious education issues, said Yasmine Farouk, an expert on Riyadh at the Carnegie Endowment for International Peace. Following the release of the report, and Biden’s policy changes, Farouk said, “That’s going to become the norm from now on, and that’s big when it comes to Saudi Arabia.”
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+If the administration targeted MBS — the king’s son and likely future king of Saudi Arabia — the US would put all that at risk. That’s just not something Biden’s team wanted to do.
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+“We believe there [are] more effective ways to make sure this doesn’t happen again and to also be able to leave room to work with the Saudis on areas where there is mutual agreement — where there is national interests for the United States,” White House press secretary Jen Psaki told CNN’s State of the Union on Sunday. “That is what diplomacy looks like.”
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+For Fontenrose, who was in the Trump White House during the Khashoggi affair, Biden ended up essentially where the former president did. “There’s literally no difference in their approach,” she told me, save for Biden avoiding the kind of crude comments Trump made about the issue. “This is just as much a get out of jail free card as MBS got from Trump.”
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+This is not to say Biden’s policy is identical to his predecessor’s or that it won’t change in the future. It’s only been a month, after all.
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+But what recent events have shown is that the president’s policies for Iran and Saudi Arabia haven’t gone as planned or as promised, which means we can all expect a change in the administration’s approaches in the days to come.
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+Sign up for The Weeds newsletter. Every Friday, you’ll get an explainer of a big policy story from the week, a look at important research that recently came out, and answers to reader questions — to guide you through the first 100 days of President Joe Biden’s administration.
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From The Hindu: Sports
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Punjab CM urges BCCI to include Mohali cricket stadium for IPL - Delhi, Ahmedabad, Kolkata, Bengaluru and Chennai have been shortlisted as potential venues but the BCCI is yet to take a final call on the matter
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ICC ‘Player of the Month’: Ashwin, Root, Mayers in contention among men - Seasoned India off-spinner Ravichandran Ashwin along with England captain Joe Root and West Indies’ new batting sensation Kyle Mayers were on Tuesday
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Mandhana slips 2 places to 6th among batters; Goswami still at 5th among bowlers in ODI rankings - Besides Goswami, Poonam Yadav, Shikha Pandey and Deepti Sharma are the other Indian bowlers in the top-10.
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Chris Gayle targets T20 World Cup defence with Windies on comeback - Gayle has kept himself busy in T20 leagues across the world
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Australia right behind England ahead of final India Test - England’s hopes of playing the WTC final were crushed with their 10-wicket defeat inside two days in an extraordinary third test in Ahmedabad.
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From The Hindu: National News
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India tells Pakistan to stop state-sponsored cross-border terrorism - India also slammed Pakistan for deliberately misusing the Council for its malicious propaganda against the country
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Kerala Tourism bid to woo domestic holidayers - Increased focus on social media to improve footfall
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CBI raids places in UP, MP in coal pilferage case - The Central Bureau of Investigation (CBI) on Tuesday conducted search operations at several places in Uttar Pradesh and Madhya Pradesh in connection
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Gold smuggling: Swapna’s bail plea to be heard today - Special Court had earlier granted bail for 12 accused and the HC had ratified it
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Kangana Ranaut moves SC seeking transfer of cases from Mumbai to Shimla - Kangana Ranaut and her sister said they apprehend if trial in these cases are conducted in Mumbai, there would be a “material threat” to their life and property
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From BBC: Europe
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Covid: France approves AstraZeneca vaccine for over-65s - Older French patients can now get the jab, which had been initially limited to those aged under 65.
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Covid: What’s the problem with the EU vaccine rollout? - The coronavirus vaccine is being rolled out across the EU but there have been delays.
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Poland activists acquitted over LGBT Virgin Mary - Three women, who faced up to two years in jail, were found not guilty of offending religious feelings.
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Volvo Cars to go fully electric by 2030 - The Swedish firm is to phase out all models with internal combustion engines over the next few years.
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Angelina Jolie sells Winston Churchill painting for record £7m - The Tower Of The Koutoubia Mosque, owned by the actress, is sold to an unidentified buyer.
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From Ars Technica
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Biden administration puts a price on carbon - The results of his first environment executive orders are coming in. - link
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Trump’s is one of 15,000 Gab accounts that just got hacked - GabLeaks includes 70,000 messages in more than 19,000 chats by over 15,000 users. - link
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Why N95 masks are still hard to get, even though production is up - Both supply and demand are up—but they aren’t lining up in the right places. - link
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“We knew T-Mobile couldn’t be trusted,” union says after 5,000 job cuts - T-Mobile claimed Sprint merger would create thousands of jobs “from day one.” - link
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Minisforum U850—solid hardware and easy upgrades in a little box - This mini-PC is VESA mountable, easy to work on, and attractively priced. - link
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Courtesy of HBO Max
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