Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Pandemics Initially Spread Among People of Higher (not Lower) Social Status: Evidence from COVID-19 and the Spanish Flu -
  According to a staple in the social sciences, pandemics particularly spread among people of lower social status. Challenging this staple, we hypothesize that it holds true in later phases of pandemics only. In the initial phases, by contrast, people of higher social status should be at the center of the spread. We tested our phase-sensitive hypothesis in two studies. In Study 1, we analyzed region-level COVID-19 infection data from 3,132 U.S. regions, 299 English regions, and 400 German regions. In Study 2, we analyzed historical data from 1,159,920 U.S. residents who witnessed the 1918/1919 Spanish Flu pandemic. For both pandemics, we found that the virus initially spread more rapidly among people of higher social status. In later phases, that effect reversed; people of lower social status were most exposed. Our results provide novel insights into the center of the spread during the critical initial phases of pandemics.
  🖺 Full Text HTML: Pandemics Initially Spread Among People of Higher (not Lower) Social Status: Evidence from COVID-19 and the Spanish Flu
• Survey evidence of excess mortality in Bihar in the second COVID-19 surge -
  The second surge of COVID-19 had a large mortality impact in India. However, there are few reliable estimates of the magnitude of this impact for India’s poorer states. This note presents results of a small-scale phone survey in Bihar which interviewed a random sample of beneficiaries of the state’s Public Distribution System. This pilot survey was conducted in June 2021 and asked more than 500 respondents about any deaths in their household since April 1, 2021.We observe an annualized Crude Death Rate of 24.3 deaths per 1,000 [95% CI 13.0-37.4] during the second surge of the pandemic in Bihar. The observed death rate is more than four times baseline mortality (5.8 deaths per 1,000 per year). The probability that mortality during the second surge was at least thrice the level of baseline mortality is 0.88. This large surge in mortality warrants an urgent public discussion on state priorities in Bihar. It also suggests the viability of and need for continuous large-scale mortality surveys.
  🖺 Full Text HTML: Survey evidence of excess mortality in Bihar in the second COVID-19 surge
• The Gender Gap in Household Tasks and Division of Labor Satisfaction During COVID-19 -
  For many years, scholars have directed our attention to the gender gap in domestic labor. Even when women engage in paid employment, they nevertheless perform the majority of the household labor in most wealthy countries. At the same time, disasters and crises both expose and exacerbate existing social inequalities. In this paper, we ask: in what ways has the COVID-19 pandemic contributed to the gender gap in household labor, including childcare? And how do men and women feel about this gap? Using data from the Canadian Perspectives survey series (Wave 3), conducted by Statistics Canada three months into the pandemic, our analyses consider the task distribution that made household labor intensely unequal during COVID-19, with women ten times more likely than men to say childcare fell mostly on them, for example. Yet, in nearly all of our models, women did not unambiguously report being more dissatisfied with the division of domestic tasks within the house, nor were they more likely than men to say that the household division of labor “got worse” during COVID, however, parents (mothers and fathers) did feel that it got worse. We discuss what these findings mean for women’s mental health, long-term paid labor, and interpersonal power, and raise questions about why it is we are not seeing a decrease in women’s reported satisfaction with this division of labor. These findings spotlight gender inequality as pillars of capitalism, and how the structural and the interpersonal weathering of the pandemic comes at women’s expense.
  🖺 Full Text HTML: The Gender Gap in Household Tasks and Division of Labor Satisfaction During COVID-19
• Web-scraping the Expression of Loneliness during COVID-19 -
  We investigated the subjective experience of loneliness during COVID-19 by analyzing social media postings from March 2020 to January 2021. We collected text data from loneliness-related subgroups of Reddit and sampled 12787 posts that were written in ten consecutive days from each month. The results suggest that when individuals express their loneliness, they show an internal focus of attention on their emotions, desires, and cognitive appraisals rather than an external focus of attention on situations or other people. Linguistic markers of emotions expressed by lonely individuals included depression, anxiety, anger, hate, helplessness, and sadness. Also, loneliness-related topics were generally about their internal states pertinent to various social relationships, interpersonal interaction deficits, and their own lives in broad time perspectives. COVID-19 related loneliness was associated with negative appraisal of one’s situation and reaching out for new relationships online.
  🖺 Full Text HTML: Web-scraping the Expression of Loneliness during COVID-19
• Locking down behavioural compliance: the role of emotion and emotion regulation in breaches of COVID-19 mitigation measures -
  Although anxiety and worry can motivate engagement with COVID-19 preventative behaviours, people may cognitively reframe these unpleasant emotions, restoring wellbeing at the cost of public health behaviours. New Zealand young adults (n=278) experiencing nationwide COVID-19 lockdown reported their worry, anxiety, reappraisal, and lockdown compliance. Despite high knowledge of lockdown policies, 92.5% of participants reported one or more policy breaches (M=2.74, SD=1.86). Counter to predictions, no relationships were found between anxiety or worry with reappraisal or lockdown breaches. Findings highlight the importance of targeting young adults in promoting lockdown compliance and offer further insight into the role of emotion during a pandemic.
  🖺 Full Text HTML: Locking down behavioural compliance: the role of emotion and emotion regulation in breaches of COVID-19 mitigation measures
• The human nose organoid respiratory virus model: an ex-vivo human challenge model to study RSV and SARS-CoV-2 pathogenesis and evaluate therapeutics -
  There is an unmet need for pre-clinical models to understand the pathogenesis of human respiratory viruses; and predict responsiveness to immunotherapies. Airway organoids can serve as an ex-vivo human airway model to study respiratory viral pathogenesis; however, they rely on invasive techniques to obtain patient samples. Here, we report a non-invasive technique to generate human nose organoids (HNOs) as an alternate to biopsy derived organoids. We made air liquid interface (ALI) cultures from HNOs and assessed infection with two major human respiratory viruses, respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Infected HNO-ALI cultures recapitulate aspects of RSV and SARS-CoV-2 infection, including viral shedding, ciliary damage, innate immune responses, and mucus hyper-secretion. Next, we evaluated the feasibility of the HNO-ALI respiratory virus model system to test the efficacy of palivizumab to prevent RSV infection. Palivizumab was administered in the basolateral compartment (circulation) while viral infection occurred in the apical ciliated cells (airways), simulating the events in infants. In our model, palivizumab effectively prevented RSV infection in a concentration dependent manner. Thus, the HNO-ALI model can serve as an alternate to lung organoids to study respiratory viruses and testing therapeutics.
  🖺 Full Text HTML: The human nose organoid respiratory virus model: an ex-vivo human challenge model to study RSV and SARS-CoV-2 pathogenesis and evaluate therapeutics
• BRET-based self-cleaving biosensors for SARS-CoV-2 3CLpro Inhibitor Discovery -
  The 3C-like protease (3CLpro) of SARS-CoV-2 is an attractive drug target for developing antivirals against SARS- CoV-2. A few small molecule inhibitors of 3CLpro are in clinical trials for COVID-19 treatments and more inhibitors are being developed. One limiting factor for 3CLpro inhibitors development is that the cellular activities of such inhibitors have to be evaluated in a Biosafety Level 3 (BSL-3) or BSL-4 laboratory. Here, we design genetically encoded biosensors that can be used in BSL-2 laboratories to set up cell-based assays for 3CLpro inhibitor discovery. The biosensors were constructed by linking a green fluorescent protein (GFP2) to the N-terminus and a Renilla luciferase (RLuc8) to the C-terminus of SARS-CoV-2 3CLpro, with the linkers derived from the cleavage sequences of 3CLpro. After over-expression of the biosensors in HEK293 cells, 3CLpro can be released from GFP2 and RLuc by self-cleavage, resulting in a decrease of the bioluminescence resonance energy transfer (BRET) signal. Using one of these biosensors, pBRET-10, we evaluated the cellular activities of several 3CLpro inhibitors. These inhibitors restored the BRET signal by blocking the proteolysis of pBRET-10, and their relative activities measured using pBRET-10 were consistent with their anti- SARS-CoV-2 activities reported previously. We conclude that the biosensor pBRET-10 is a useful tool for SARS-CoV-2 3CLpro inhibitor discovery. Furthermore, our strategy can be used to design biosensors for other viral proteases that share the same activation mechanism as 3CLpro, such as HIV protease PR and HCV protease NS3.
  🖺 Full Text HTML: BRET-based self-cleaving biosensors for SARS-CoV-2 3CLpro Inhibitor Discovery
• The Achilles’ heel of coronaviruses: targeting the 5’ Polyuridines tract of the antigenome to inhibit Mouse coronavirus virus-induced cell death -
  The current coronavirus pandemic situation is worsened by the rapidly-spreading SARS-CoV-2 virus variants. Identification of viral targets that are indispensable for the virus can be targeted to inhibit mutation-based new escape variant development. The 5’-polyU tract of the antigenome offers such a target. Host cells do not harbor 5’-polyU tracts on any of their transcripts, making the tract an attractive, virus-specific target. Inhibiting the 5’-polyU can limit the use of the tract as template to generate 3’ polyA tails of +RNAs of coronaviruses. Here, a modified DNA oligo with 3’ polyAs is used to target the 5’-polyU tract in mouse coronavirus (MHV-A59). The oligo treatment in mouse 17CL-1 cells infected with MHV-A59 significantly prevented virus-induced cell deaths. This proof-of-concept result shows a unique mode of action against mouse coronavirus without affecting host cells, and can be used for the development of novel classes of drugs that inhibit coronavirus infection in host cells, specifically by the COVID-19-causing virus SARS-CoV-2. In addition, as the 5’-polyU tract is immediately generated upon infection, the tag can also be targeted for reliable early detection of viral infection.
  🖺 Full Text HTML: The Achilles’ heel of coronaviruses: targeting the 5’ Polyuridines tract of the antigenome to inhibit Mouse coronavirus virus-induced cell death
• SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance -
  SARS-CoV-2 Lambda, a new variant of interest, is now spreading in some South American countries; however, its virological features and evolutionary trait remain unknown. Here we reveal that the spike protein of the Lambda variant is more infectious and it is attributed to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion mutation in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the insertion of the RSYLTPGD246-253N mutation is closely associated with the massive infection spread of the Lambda variant in South America.
  🖺 Full Text HTML: SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance
• SARS-CoV-2 in the Republic of Guinea: Fragment and Whole-Genome Sequencing, Phylogenetic Analysis -
  Genetic diversity of SARS-CoV-2 isolates circulating in the Republic of Guinea in May and June 2020, as well as in March 2021, has been demonstrated using fragment (S gene) and whole genome sequencing of 14 strains. Analysis of nucleotide sequences and phylogenetic constructs make it possible to divide the studied strains into 3 groups. Comparison of the obtained data with the already available epidemiological data proves the initial importation of COVID-19 from Western European countries, and also demonstrates four independent import routes in two time periods (March 2020 and no later than March 2021).
  🖺 Full Text HTML: SARS-CoV-2 in the Republic of Guinea: Fragment and Whole-Genome Sequencing, Phylogenetic Analysis
• Single-Cell Profiling of the Antigen-Specific Response to BNT162b2 SARS-CoV-2 RNA Vaccine -
  RNA-based vaccines against SARS-CoV-2 are critical to limiting COVID-19 severity and spread. Cellular mechanisms driving antigen-specific responses to these vaccines, however, remain uncertain. We used single-cell technologies to identify and characterized antigen-specific cells and antibody responses to the RNA vaccine BNT162b2 in a longitudinal cohort of healthy donors. Mass cytometry and machine learning pinpointed a novel expanding, population of antigen- specific non-canonical memory CD4+ and CD8+ T cells. B cell sequencing suggested progression from IgM, with apparent cross-reactivity to endemic coronaviruses, to SARS-CoV-2-specific IgA and IgG memory B cells and plasmablasts. Responding lymphocyte populations correlated with eventual SARS-CoV-2 IgG and a donor lacking these cell populations failed to sustain SARS-CoV-2-specific antibodies and experienced breakthrough infection. These integrated proteomic and genomic platforms reveal an antigen-specific cellular basis of RNA vaccine-based immunity.
  🖺 Full Text HTML: Single-Cell Profiling of the Antigen-Specific Response to BNT162b2 SARS-CoV-2 RNA Vaccine
• A Partition-Based Group Testing Algorithm for Estimating the Number of Infected Individuals -

  The dangers of COVID-19 remain ever-present worldwide. The asymptomatic nature of COVID-19 obfuscates the signs policy makers look for when deciding to reopen public areas or further quarantine. In much of the world, testing resources are often scarce, creating a need for testing potentially infected individuals that prioritizes efficiency. This report presents an advancement to Beigel and Kasif9s Approximate Counting Algorithm (ACA). ACA estimates the infection rate with a number of tests that is logarithmic in the population size. Our newer version of the algorithm provides an extra level of efficiency: each subject is tested exactly once. A simulation of the algorithm, created for and presented as part of this paper, can be used to find a linear regression of the results with R^2 > 0.999. This allows stakeholders and members of the biomedical community to estimate infection rates for varying population sizes and ranges of infection rates.

  🖺 Full Text HTML: A Partition-Based Group Testing Algorithm for Estimating the Number of Infected Individuals
• Change in Symptoms and Immune Response in People with Post-Acute Sequelae of SARS-Cov-2 Infection (PASC) After SARS- Cov-2 Vaccination -

  As more people are vaccinated against SARS-CoV-2, many of those already infected are still suffering from Post- Acute Sequelae (PASC). Although there is no current treatment for PASC, reports from patients that the vaccine itself improves, and in some reports, worsens, PASC symptoms may lead to a deeper understanding of the causes of PASC symptoms and viable treatments. As such, we are conducting a study that measures the changes in PASC symptoms after vaccination. We are collecting baseline self-report and biospecimens for immune assays and then are following up with participants to collect the same data at 2-weeks, 6-weeks, and 12-weeks post-vaccination (first dose). Immune assays using blood specimens will include B-cell, T-cell, and myeloid cell panels; evaluation of T-cell responsiveness to SARS-CoV-2 peptides and antigen specific response; autoantibody screening (of IgG, IgM, and IgA antibodies that attack human proteins); and TCR sequencing and antigen mapping of CD8+ T-cells. Mucosal immunity will be measured using saliva specimens. The study aims to provide answers for people with PASC, especially regarding the causes of their symptoms and how the vaccine may affect them, and clues for PASC treatment.

  🖺 Full Text HTML: Change in Symptoms and Immune Response in People with Post-Acute Sequelae of SARS-Cov-2 Infection (PASC) After SARS-Cov-2 Vaccination
• Monitoring and forecasting the SARS-Covid-19 pandemic in France -

  Over the past year, many countries have resorted multiple times to drastic social restrictions to prevent saturation of their health care system, and to regain control over an otherwise exponentially increasing SARS-Covid-19 pandemic evolution. With the advent of data-sharing, computational approaches have gained a key role in evaluating future scenarios and offering predictions in a constantly evolving social environment. To design optimal social, hospitalization and economical strategies that guarantee control over the pandemic progression, we developed a data- driven modelling framework with the aim to provide reliable near future predictions under constantly evolving social and pandemic events. The framework is flexible enough to be used at a single hospital, regional or national level. We used a variety of data such as social, serological, testing and clinical data to compute the infection dynamics and the hospital workload for France. We developed inference methods to calibrate model parameters from observed hospitalization statistics over adjustable time periods. We applied our model to study the age stratified pandemic evolution inside and outside hospitals until February 2021, and the competition between vaccinations and the novel delta variant. We obtained several predictions about hidden pandemic properties such as fractions of infected, infection hospitality and infection fatality ratios. We show that reproduction numbers and herd immunity levels are not universal but strongly depend on the underlying social dynamics. We find that with normal social interactions the present vaccination status and rate is not sufficient to prevent a new pandemic wave driven by the delta variant.

  🖺 Full Text HTML: Monitoring and forecasting the SARS-Covid-19 pandemic in France
• COVID-19 Disease Severity among People with HIV Infection or Solid Organ Transplant in the United States: A Nationally-representative, Multicenter, Observational Cohort Study -

  Background Individuals with immune dysfunction, including people with HIV (PWH) or solid organ transplant recipients (SOT), might have worse outcomes from COVID-19. We compared odds of COVID-19 outcomes between patients with and without immune dysfunction. Methods We evaluated data from the National COVID-19 Cohort Collaborative (N3C), a multicenter retrospective cohort of electronic medical record (EMR) data from across the United States, on. 1,446,913 adult patients with laboratory-confirmed SARS-CoV-2 infection. HIV, SOT, comorbidity, and HIV markers were identified from EMR data prior to SARS-CoV-2 infection. COVID-19 disease severity within 45 days of SARS-CoV-2 infection was classified into 5 categories: asymptomatic/mild disease with outpatient care; mild disease with emergency department (ED) visit; moderate disease requiring hospitalization; severe disease requiring ventilation or extracorporeal membrane oxygenation (ECMO); and death. We used multivariable, multinomial logistic regression models to compare odds of COVID-19 outcomes between patients with and without immune dysfunction. Findings Compared to patients without immune dysfunction, PWH and SOT had a greater likelihood of having ED visits (adjusted odds ratio [aOR]: 1.28, 95% confidence interval [CI] 1.27-1.29; aOR: 2.61, CI: 2.58-2.65, respectively), requiring ventilation or ECMO (aOR: 1.43, CI: 1.43-1.43; aOR: 4.82, CI: 4.78-4.86, respectively), and death (aOR: 1.20, CI: 1.19-1.20; aOR: 3.38, CI: 3.35-3.41, respectively). Associations were independent of sociodemographic and comorbidity burden. Compared to PWH with CD4>500 cells/mm3, PWH with CD4<350 cells/mm3 were independently at 4.4-, 5.4-, and 7.6-times higher odds for hospitalization, requiring ventilation, and death, respectively. Increased COVID-19 severity was associated with higher levels of HIV viremia. Interpretation Individuals with immune dysfunction have greater risk for severe COVID-19 outcomes. More advanced HIV disease (greater immunosuppression and HIV viremia) was associated with higher odds of severe COVID-19 outcomes. Appropriate prevention and treatment strategies should be investigated to reduce the higher morbidity and mortality associated with COVID-19 among PWH and SOT.

  🖺 Full Text HTML: COVID-19 Disease Severity among People with HIV Infection or Solid Organ Transplant in the United States: A Nationally- representative, Multicenter, Observational Cohort Study

From Clinical Trials

• Phase II/III Study of AZD2816, for the Prevention of COVID-19 in Adults - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Biological: AZD1222;   Biological: AZD2816
  Sponsor:   AstraZeneca
  Recruiting

• Building Resiliency and Vital Equity (BRAVE) Project: Understanding Native Americans’ Perceptions/Beliefs About COVID-19 Testing and Vaccination Study - Condition:   Covid19 Virus Infection
  Intervention:   Behavioral: Protect Your Elders Campaign
  Sponsors:   North Carolina Central University;   Lumbee Tribe of North Carolina;   University of North Carolina at Pembroke
  Recruiting

• Effects of Respiratory Muscle Training in Patients With Post COVID-19 - Condition:   Covid19
  Interventions:   Other: Exercise training group;   Other: Control training group
  Sponsor:   Gazi University
  Completed

• SOLIDARITY Finland Long COVID-19 - Condition:   Covid19
  Intervention:   Drug: Remdesivir
  Sponsors:  
  Clinical Urology and Epidemiology Working Group;   University of Helsinki;   World Health Organization;   Helsinki University Central Hospital;   Hyvinkää Hospital;   Kanta-Häme Central Hospital;   Kuopio University Hospital;   Oulu University Hospital;   Porvoo Hospital;   Seinajoki Central Hospital;   Mikkeli Central Hospital;   Tampere University Hospital
  Recruiting

• Vaccination for Recovered Inpatients With COVID-19 (VATICO) - Condition:   Covid19
  Interventions:   Biological: Moderna mRNA-1273 COVID-19 vaccine;   Biological: Pfizer BNT162b2 COVID-19 vaccine
  Sponsors:   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Minnesota;   National Institute of Allergy and Infectious Diseases (NIAID);   University of Copenhagen;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Medical Research Council
  Not yet recruiting

• Enabling Family Physicians to Reduce Vaccine Hesitancy and Increase Covid-19 Vaccine Uptake - Conditions:   Covid19;   COVID-19 Vaccine
  Interventions:  
  Behavioral: Tailored COVID-19 vaccine messages;   Other: Other health messages
  Sponsors:  
  Hopital Montfort;   Public Health Agency of Canada (PHAC);   Eastern Ontario Health Unit
  Not yet recruiting

• Efficacy of Canrenone as add-on Treatment in Moderate to Severe ARDS in COVID-19 - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:  
  Drug: Potassium Canrenoate
  Sponsors:   Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico;   University of Milan;   IRCCS Azienda Ospedaliero-Universitaria di Bologna
  Not yet recruiting

• COVID-19 and Lung Ultrasound Utility - Condition:   Covid19
  Intervention:   Device: Device: Butterfly iQ
  Sponsor:  
  Rocket Doctor Inc.
  Recruiting

• Booster Vaccination Against SARS-CoV-2 - Condition:   Covid19
  Intervention:   Biological: CoronaVac
  Sponsor:  
  Health Institutes of Turkey
  Recruiting

• Saliva-based COVID-19 DNA Aptamer Test - Condition:   Covid19
  Intervention:   Device: AptameX
  Sponsors:   Achiko AG;   Udayana University
  Recruiting

• Baricitinib in Hospitalized Covid-19 Patients With Diabetes Mellitus - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Baricitinib;   Drug: Dexamethasone;   Drug: Remdesivir
  Sponsor:   Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders
  Recruiting

• Evaluation of the RD-X19 Treatment Device in Individuals With Mild to Moderate COVID-19 - Condition:   COVID19
  Interventions:   Device: RD-X19;   Device: Sham
  Sponsor:  
  EmitBio Inc.
  Recruiting

• Evaluation of The Efficacy of Triazavirin Versus Oseltamivir in Egyptian Patients Infected With COVID-19 - Condition:   Covid19
  Intervention:   Drug: standard treatment COVID-19 + Triazavirin
  Sponsor:   Ain Shams University
  Recruiting

• Hidroxicloroquina With Azitromicina Versus Hidroxicloroquina and Placebo Int Patients With Mild COVID-19 - Condition:   Covid19
  Intervention:   Drug: Hydroxychloroquine with Azithromycin
  Sponsors:   Coordinación de Investigación en Salud, Mexico;   Ultra Laboratorios SA. de CV.
  Recruiting

• Study to Evaluate the Immunogenicity and Safety of Heterologous SARS-CoV-2 Vaccine Schemes - Condition:   COVID-19 Vaccines
  Intervention:   Drug: Gam-COVID-Vac / Gam-COVID-Vac
  Sponsor:   Ministerio de Salud de Ciudad Autónoma de Buenos Aires
  Recruiting

From PubMed

• One microsecond MD simulations of the SARS-CoV-2 main protease and hydroxychloroquine complex reveal the intricate nature of binding - Currently, several vaccines and antivirals across the globe are in clinical trials. Hydroxychloroquine (HCQ) was reported to inhibit the SARS-CoV-2 virus in antiviral assays. Here, it raises the curiosity about the molecular target of HCQ inside the cell. It may inhibit some of the viral targets, or some other complex mechanisms must be at disposal towards action mechanisms. In some of the viruses, proteases are experimentally reported to be a potential target of HCQ. However, no in-depth…

• Losartan Inhibits SARS-CoV-2 Replication in Vitro - CONCLUSION: Losartan was not an effective inhibitor of deubiquitinase or deISGylase activity of the PLpro but affected the SARS-CoV-2 replication of Vero E6 cells in vitro. As losartan has a favorable safety profile and is currently available it has features necessary for efficacious drug repurposing and treatment of COVID-19.

• Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir - Rapid repurposing of existing drugs as new therapeutics for COVID-19 has been an important strategy in the management of disease severity during the ongoing SARS-CoV-2 pandemic. Here, we used high-throughput docking to screen 6000 compounds within the DrugBank library for their potential to bind and inhibit the SARS-CoV-2 3 CL main protease, a chymotrypsin- like enzyme that is essential for viral replication. For 19 candidate hits, parallel in vitro fluorescence-based protease-inhibition assays…

• The potential role of neopterin in Covid-19: a new perspective - Neopterin (NPT) is a member of pteridines group, synthesized by macrophages when stimulated by interferon gamma (INF-γ). NPT is regarded as a macrophage stimulation indicator, marker of cellular immune activation and T helper 1 (Th1) type 1 immune response. Here, we aimed to provide a view point on the NPT features and role in Covid-19. Serum NPT level is regarded as an independent prognostic factor for Covid-19 severity, with levels starting to increase from the 3rd day of SARS-CoV-2 infection,…

• A Novel Small Molecule Inhibits Hepatitis C Virus Propagation in Cell Culture - Hepatitis C virus (HCV) can cause acute and chronic infection that is associated with considerable liver-related morbidity and mortality. In recent years, there has been a shift in the treatment paradigm with the discovery and approval of agents that target specific proteins vital for viral replication. We employed a cell culture-adapted strain of HCV and human hepatoma-derived cells lines to test the effects of our novel small-molecule compound (AO13) on HCV. Virus inhibition was tested by…

• SARS-CoV-2 Antiviral Therapy - The development of effective antiviral therapy for COVID-19 is critical for those awaiting vaccination, as well as for those who do not respond robustly to vaccination. This review summarizes 1 year of progress in the race to develop antiviral therapies for COVID-19, including research spanning preclinical and clinical drug development efforts, with an emphasis on antiviral compounds that are in clinical development or that are high priorities for clinical development. The review is divided into…

• Ivermectin for preventing and treating COVID-19 - BACKGROUND: Ivermectin, an antiparasitic agent used to treat parasitic infestations, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin’s antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the early stages of infection. Currently, evidence on efficacy and safety of ivermectin for prevention of SARS-CoV-2 infection and COVID-19 treatment is conflicting.

• The iron(III) and nickel(II) complexes with tetradentate thiosemicarbazones. Synthesis, experimental, theoretical characterization, and antiviral effect against SARS-Cov2 - The discovery of new inhibitors that can be used in the treatment of viral diseases, including Covid-19, is an area open to research, and there is a need for innovative compounds with increased efficiency that provide inhibition by suppressing enzyme, and receptor mechanisms. The iron(III) and nickel(II) complexes were synthesized by template condensation of 4-methoxy-salicylaldehyde with S-methylthiosemicarbazone derivatives of 1,1,1-trifluoroacetylacetone (for Fe1) and methylacetoacetate (for…

• Author Correction: Targeting novel LSD1-dependent ACE2 demethylation domains inhibits SARS-CoV-2 replication - No abstract

• SARS-CoV-2 infection triggers widespread host mRNA decay leading to an mRNA export block - The transcriptional induction of interferon (IFN) genes is a key feature of the mammalian antiviral response that limits viral replication and dissemination. A hallmark of severe COVID-19 disease caused by SARS-CoV-2 is the low presence of IFN proteins in patient serum despite elevated levels of IFN-encoding mRNAs, indicative of post-transcriptional inhibition of IFN protein production. Here, we performed single-molecule RNA visualization to examine the expression and localization of host mRNAs…

• Remdesivir analogs against SARS-CoV-2 RNA-dependent RNA polymerase - The COVID-19 pandemic has already taken many lives but is still continuing its spread and exerting jeopardizing effects. This study is aimed to find the most potent ligands from 703 analogs of remdesivir against RNA-dependent RNA polymerase (RdRp) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus . RdRp is a major part of a multi- subunit transcription complex of the virus, which is essential for viral replication. In clinical trials, it has been found that remdesivir…

• Aberrant glycosylation of anti-SARS-CoV-2 IgG is a pro-thrombotic stimulus for platelets - A subset of patients with COVID-19 become critically ill, suffering from severe respiratory problems and also increased rates of thrombosis. The causes of thrombosis in severely ill COVID-19 patients are still emerging, but the coincidence of critical illness with the timing of the onset of adaptive immunity could implicate an excessive immune response. We hypothesised that platelets might be susceptible to activation by anti-SARS-CoV-2 antibodies and contribute to thrombosis. We found that…

• Network pharmacology and molecular docking analysis on mechanisms of Tibetan Hongjingtian (Rhodiola crenulata) in the treatment of COVID-19 - Introduction. Coronavirus disease 2019 (COVID-19) is a highly contagious disease and ravages the world.Hypothesis/Gap Statement. We proposed that R. crenulata might have potential value in the treatment of COVID-19 patients by regulating the immune response and inhibiting cytokine storm.Aim. We aimed to explore the potential molecular mechanism for Rhodiola crenulata (R. crenulata), against the immune regulation of COVID-19, and to provide a referenced candidate Tibetan herb (R. crenulata) to…

• Application of nano-graphene oxide as nontoxic disinfectant against alpha and betacoronaviruses - New viruses are continuously emerging and recently there have been many great concerns on severe acute respiratory syndrome coronavirus (SARS-CoV-2). Nanographene oxide (nanoGO) has received much attention and is widely investigated to be utilised in therapy for infectious diseases by viruses. Thus, antiviral activity of nanoGO was evaluated using the porcine epidemic diarrhoea virus (PEDV), bovine coronavirus (BCoV), and SARS-CoV-2, which are all Alpha- and Beta- coronavirus. In a virus…

• Natural Products with tandem Anti-inflammatory, Immunomodulatory and Anti-SARS-CoV/2 effects: A Drug Discovery Perspective against SARS-CoV-2 - CONCLUSION: This study revealed that amentoflavone, rubranoside B, savinin, psoralidin, hirsutenone, and papyriflavonol A are good drug candidate for the search of antibiotics against COVID-19.

From Patent Search

• A SYSTEM AND METHOD FOR COVID- 19 DIAGNOSIS USING DETECTION RESULTS FROM CHEST X- RAY IMAGES - - link

• Advanced Machine Learning System combating COVID-19 virus Detection, Spread, Prevention and Medical Assistance. - - link

• 一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用 - 本发明提供了一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用，涉及生物医药技术领域。本发明利用A型流感病毒八个基因片段为骨架包装出带有新型冠状病毒SARS‑CoV‑2表面刺突蛋白受体结合域（SARS‑CoV‑2_RBD）片段的重组流感病毒，此重组流感病毒可在复制过程中表达具有生物学活性和免疫原性的刺突蛋白受体结合区域RBD。本发明所述重组流感病毒rgH1N1（PR8）‑PA‑RBD可作为重组病毒类药物，用于2019新型冠状病毒肺炎（COVID‑19）的预防；也可作为体外SARS‑COV‑2 RBD等相关抗原表达和体内递呈系统。 - link

• Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link

• 一种新型冠状病毒的mRNA疫苗 - 本发明公开了一种新型冠状病毒的mRNA疫苗。本发明提供的疫苗，其活性成分为mRNA，如序列表的序列6所示。本发明还保护TF‑RBD蛋白，如序列表的序列2所示。本发明的发明人通过一系列序列设计和序列优化得到了特异DNA分子，进一步构建了特异重组质粒，将特异重组质粒进行体外转录，可以得到多聚化TF‑RBD mRNA。进一步的，发明人制备了负载TF‑RBD mRNA的脂质纳米粒。本发明对于新型冠状病毒的防控具有重大的应用推广价值。 - link

• 新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用。本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因，其核苷酸序列如SEQ ID NO.1或SEQ ID NO.6所示。本发明通过优化野生型新型冠状病毒B．1．1．7英国突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B．1．1．7英国突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因更有利于用于制备新型冠状病毒疫苗。 - link

• SARS-CoV-2 anti-viral therapeutic - - link

• 一种基于联邦学习的多用户协同训练人流统计方法及系统 - 本发明提供一种基于联邦学习的多用户协同训练人流统计方法，旨在利用联邦学习框架搭建一个新颖的人群计数模型，达到让多用户多设备同时训练的目的。各个客户端利用图像数据集对图像分类网络进行本地训练以获取本地模型；在各经过至少一次本地训练后，中心服务器从客户端获取本地模型的权值及附加层参数并进行聚合处理；中心服务器利用聚合处理后的权值及附加层参数更新全局模型，并将聚合处理后的权值参数及附加层参数返回给各个客户端；各个客户端利用中心服务器返回的权值以及ground truth值进行贝叶斯估计，计算loss值，并利用返回的权值参数及附加层参数更新本地模型；重复执行直至所有客户端的loss值均收敛，则完成人流统计全局模型和本地模型的训练。 - link

• A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link

• 新型冠状病毒B.1.351南非突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.351南非突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.351南非突变株RBD的基因，其核苷酸序列如SEQIDNO.1或SEQIDNO.6所示。本发明通过优化野生型新型冠状病毒南非B.1.351南非突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.351南非突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.351南非突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link