Covid-19 Sentry

Contents

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

From Preprints

• Predicted impact of the COVID-19 pandemic on global tuberculosis deaths in 2020 -

  Policies widely adopted in response to the ongoing pandemic of Covid-19, particularly lockdowns and reassignments of health personnel and equipment, are impacting the performance of TB prevention and care programmes at a level varying significantly between countries. Estimates of the impact of reductions in the performance of global TB detection and care on TB mortality are presented.

  🖺 Full Text HTML: Predicted impact of the COVID-19 pandemic on global tuberculosis deaths in 2020
• Angiotensin converting enzyme 2 (ACE2) is expressed in murine cutaneous under single-cell transcriptome resolution -
  Angiotensin converting enzyme 2 (Ace2) is widely distributed in human organs, which was identified as a functional receptor for severe acute respiratory syndrome (SARS) coronavirus in human beings. It was also confirmed that SARS-CoV-2 uses the same cell entry receptor, ACE2, as SARS-CoV. However, related research still not discover the expression data associated with murine skin under single cell RNA resolution. In this study, we performed single-cell RNA sequencing (scRNA-seq) on unsorted cells from mouse dorsal skin after 7 days post-wounding. 8312 sequenced cells from four skin samples met quality control metrics and were analyzed.
  🖺 Full Text HTML: Angiotensin converting enzyme 2 (ACE2) is expressed in murine cutaneous under single-cell transcriptome resolution
• Inhibition of SARS-CoV-2 spike protein palmitoylation reduces virus infectivity -
  Spike glycoproteins of almost all enveloped viruses are known to undergo post-translational attachment of palmitic acid moieties. The precise role of such palmitoylation of the spike protein in membrane fusion and infection is not completely understood. Here, we report that palmitoylation of the first five cysteine residues of the c-terminal cysteine-rich domain of the SARS-CoV-2 spike are indispensable for infection, and palmitoylation deficient spike mutants are defective in trimerization and subsequent membrane fusion. The DHHC9 palmitoyltransferase interacts with and palmitoylates the spike protein in the ER and Golgi, and knockdown of DHHC9 results in reduced fusion and infection of SARS-CoV-2. Two bis-piperazine backbone-based DHHC9 inhibitors inhibit SARS-CoV-2 spike protein palmitoylation and the resulting progeny virion particles released are defective in fusion and infection. This establishes these palmitoyltransferase inhibitors as potential new intervention strategies against SARS-CoV-2.
  🖺 Full Text HTML: Inhibition of SARS-CoV-2 spike protein palmitoylation reduces virus infectivity
• Non-invasive Imaging of Sense of Smell by Tracking the Voltage-Gated Sodium Channel NaV1.7 -
  Background: Anosmia/hyposmia affects 13.3 million people in the U.S. alone according to the recent U.S. National Health and Nutrition Examination Survey (NHANES). Hundreds of thousands more people with persistent olfactory dysfunction will be added to this number due to the COVID-19 pandemic. Patients with loss-of-function mutations in SCN9A, the gene encoding NaV1.7, experience anosmia in addition to congenital insensitivity to pain. Tsp1a is a recently discovered peptide that inhibits NaV1.7 with high potency and selectivity. In this study, we examined whether a fluorescently tagged version of Tsp1a could be used to visualize normal and damaged mouse olfactory nerves. Methods: Athymic nude mice were intravenously injected with Tsp1a-IR800. As a control, mice were injected with PBS only, and as a blocking control were injected with combination of Tsp1a and Tsp1a-IR800. All mice were imaged in-vivo and epifluorescence images were acquired using an IVIS Spectrum animal imaging system. Semiquantitative analysis of the Tsp1a-IR800 signal was conducted by measuring the average radiant efficiency in the region of the olfactory epithelium/bulb (ROEB). Methimazole was used to chemically ablate the olfactory epithelium. We performed a food buried test to correlate the level of anosmia with the level of radiance efficiency. Results: The area of olfactory epithelium/bulb was clearly visible in epifluorescence in-vivo images of mice receiving the imaging agent. The radiant efficiency was significantly less in both mice injected with PBS and in mice injected with the blocking formulation. The mice after olfactory ablation had a significantly reduced radiant efficiency compared with normal mice. Moreover, there was a statistically significant and inverse correlation between the time required for the mouse to find buried food and the radiant efficiency. We also performed immunohistochemistry using NaV1.7 antibody. Mice after olfactory ablation as well as COVID-19-infected mice had significantly lower expression of NaV1.7 on the level of olfactory epithelium/bulb. Conclusion: We show that the fluorescent imaging of mouse olfactory epithelium/bulb is possible, suggesting that labeled Tsp1a tracers may serve as the first objective diagnostic tool of smell disorders, including those caused by COVID-19.
  🖺 Full Text HTML: Non-invasive Imaging of Sense of Smell by Tracking the Voltage-Gated Sodium Channel NaV1.7
• A bacteria-based assay to study SARS-CoV-2 protein-protein interactions -
  Methods for detecting and dissecting the interactions of virally encoded proteins are essential for probing basic viral biology and providing a foundation for therapeutic advances. The dearth of targeted therapeutics for the treatment of COVID-19, an ongoing global health crisis, underscores the importance of gaining a deeper understanding of the interactions of SARS-CoV-2-encoded proteins. Here we describe the use of a convenient bacteria-based two-hybrid (B2H) system to analyze the SARS-CoV-2 proteome. We identify sixteen distinct intraviral protein-protein interactions (PPIs), involving sixteen proteins. We find that many of the identified proteins interact with more than one partner. We further show how our system facilitates the genetic dissection of these interactions, enabling the identification of selectively disruptive mutations. We also describe a modified B2H system that permits the detection of disulfide bond- dependent PPIs in the normally reducing Escherichia coli cytoplasm and we use this system to detect the interaction of the SARS-CoV-2 spike protein receptor-binding domain (RBD) with its cognate cell surface receptor ACE2. We then examine how the RBD-ACE2 interaction is perturbed by several RBD amino acid substitutions found in currently circulating SARS- CoV-2 variants. Our findings illustrate the utility of a genetically tractable bacterial system for probing the interactions of viral proteins and investigating the effects of emerging mutations. In principle, the system could also facilitate the identification of potential therapeutics that disrupt specific interactions of virally encoded proteins. More generally, our findings establish the feasibility of using a B2H system to detect and dissect disulfide bond- dependent interactions of eukaryotic proteins.
  🖺 Full Text HTML: A bacteria-based assay to study SARS- CoV-2 protein-protein interactions
• Gender Gaps in the Chilean Young Investigator Grant and the Potential Impact of COVID-19 Lockdowns in 2020 -
  Gender gaps are a problem in academia and impede the advancement of women. For example, women have lower application and success rates than men in many grant competitions, which has been shown for different countries and funding schemes. We analysed gender gaps in the Chilean Young Investigator Grant (Fondecyt de Iniciación en Investigación) from 2010 to 2020 and explored the potential impact of COVID-19 lockdowns in 2020. Our findings show an overall significant gender gap in success rates, which varies over the years and differs between disciplines. In 2020, the share of female applicants increased nonsignificantly, and there was a significant decrease of applicants under 40 years. This may indicate that women with small children applied less than usual. Our results imply that funding bodies and policymakers should implement new measures to reduce gender gaps and that the pandemic may particularly affect young female scientists.
  🖺 Full Text HTML: Gender Gaps in the Chilean Young Investigator Grant and the Potential Impact of COVID-19 Lockdowns in 2020
• Estimating the effectiveness of first dose of COVID-19 vaccine against mortality in England: a quasi-experimental study -

  Background: Estimating real-world vaccine effectiveness is vital to assess the impact of the vaccination programme on the pandemic and inform the ongoing policy response. However, estimating vaccine effectiveness using observational data is inherently challenging because of the non-randomised design and the potential for unmeasured confounding. Methods: We used a Regression Discontinuity Design (RDD) to estimate vaccine effectiveness against COVID-19 mortality in England, exploiting the discontinuity in vaccination rates resulting from the UK9s age-based vaccination priority groups. We used the fact that people aged 80 or over were prioritised for the vaccine roll-out in the UK to compare the risk of COVID-19 and non-COVID-19 death in people aged 75-79 and 80-84. Findings: The prioritisation of vaccination of people aged 80 or above led to a large discrepancy in vaccination rates in people 80-84 compared to those 75-79 at the beginning of the vaccination campaign. We found a corresponding difference in COVID-19 mortality, but not in non-COVID-19 mortality, suggesting that our approach appropriately addresses the issue of unmeasured confounding factors. Our results suggest that the first vaccine dose reduced the risk of COVID-19 death by 52.6% (95% Cl 26.6-84.2) in those aged 80. Interpretations: Our results support existing evidence that a first dose of a COVID-19 vaccine has a strong protective effect against COVID-19 mortality in older adults. The RDD estimate of vaccine effectiveness is comparable to previously published studies using different methods, suggesting that unmeasured confounding factors are unlikely to substantially bias these studies.

  🖺 Full Text HTML: Estimating the effectiveness of first dose of COVID-19 vaccine against mortality in England: a quasi-experimental study
• Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California -

  Associations between vaccine breakthrough cases and infection by SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analyzed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from February 1 to June 30, 2021, of which 125 (9.1%) were vaccine breakthrough infections. Fully vaccinated were more likely than unvaccinated persons to be infected by variants carrying mutations associated with decreased antibody neutralization (L452R, L452Q, E484K, and/or F490S) (78% versus 48%, p = 1.96e-08), but not by those associated with increased infectivity (L452R and/or N501Y) (85% versus 77%, p = 0.092). Differences in viral loads were non-significant between unvaccinated and fully vaccinated persons overall (p = 0.99) and according to lineage (p = 0.09 - 0.78). Viral loads were significantly higher in symptomatic as compared to asymptomatic vaccine breakthrough cases (p < 0.0001), and symptomatic vaccine breakthrough infections had similar viral loads to unvaccinated infections (p = 0.64). In 5 cases with available longitudinal samples for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to immunocompromised state or infection by an antibody-resistant lineage. These findings suggest that vaccine breakthrough cases are preferentially caused by circulating antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as unvaccinated infections, regardless of the infecting lineage.

  🖺 Full Text HTML: Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California
• Standardized incidence ratio of the COVID-19 pandemic: a case study in a Midwestern state -

  The Coronavirus disease 2019 (COVID19) has made a dramatic impact around the world with some communities facing harsher outcomes than others. We sought to understand how each county fared compared to what would be expected and what factors contributed to negative outcomes from the pandemic in South Dakotas counties. The Standardized incidence ratios of all counties using age adjusted hospitalization and death rates are computed. In addition, a penalized generalized linear regression model is used to identify factors that have an association with COVID19 hospitalization and death rates. The results identified counties that had more severe outcomes than what would be expected. In addition, race, education, and testing rate were some of the significant factors associated with the outcome.

  🖺 Full Text HTML: Standardized incidence ratio of the COVID-19 pandemic: a case study in a Midwestern state
• How the COVID-19 pandemic impacted the perception of climate change in the UK -
  Forthcoming in American Behavioral Scientist (ABS) The COVID-19 pandemic erupted during the climate change (CC) crisis, forcing individuals to adapt abruptly to a new scenario, and triggering changes in everyone’s lifestyles. Based on a representative sample of the UK population (N= 1013) this paper investigates how the COVID-19 pandemic invited/forced individuals to reflect upon a new sustainable way of life and to (re)consider the anthropogenic impact on the environment. The results show that age and education are negatively associated with skepticism relating to the human impact on CC, while other control variables such as income, gender and employment status, have a limited impact on this attitude toward CC. Secondly, findings indicate a clear separation between those with a minimal standard of education, who support the natural origin of CC, while individuals with a higher level of education believe that CC is caused by human actions. Finally, on average, younger and more educated individuals tend to associate the COVID-19 pandemic with an opportunity to promote an eco-friendly world and to adopt an eco-sustainable approach.
  🖺 Full Text HTML: How the COVID-19 pandemic impacted the perception of climate change in the UK
• Psychopathology and Perceived Discrimination Among Chinese International Students One Year into COVID-19: A Preregistered Comparative Study -
  Background and Objectives: During the COVID-19 pandemic, Chinese international students (CISs) experienced increased distress associated with a combination of unique and universal stressors, among which discrimination against Chinese is especially harmful. Therefore, studying correlates of distress among CISs, including the association between discrimination and distress and factors intensifying or attenuating this link, may yield important insights into prevention and intervention efforts. Design: We adopted a cross-sectional self-report design. Methods: Our study compared depression and anxiety between CISs (N = 381) and Chinese students in Chinese colleges (CSCCs; N = 306) and examined correlates of distress including the association between discrimination and distress as well as moderators on this link within CISs. Results: Compared to CSCCs, CISs reported greater depression and anxiety. Depression was associated with being female, older, non-heterosexual, increased discrimination, decreased self- esteem, coping flexibility, perceived social support, and satisfaction with online learning. Anxiety was associated with being female, heterosexual, in undergraduate years, increased discrimination, decreased self-esteem, subjective socioeconomic status, coping flexibility, and satisfaction with online learning. High perceived social support and being heterosexual weakened the association between discrimination and distress (anxiety and depression). Conclusions: Our study underscored the impact of the pandemic and related discrimination on CISs and highlighted individual differences that may warrant attention.
  🖺 Full Text HTML: Psychopathology and Perceived Discrimination Among Chinese International Students One Year into COVID-19: A Preregistered Comparative Study
• Genomic Surveillance in Japan of AY.29—A New Sub-lineage of SARS-CoV-2 Delta Variant with C5239T and T5514C Mutations -

  In the present study, we report a new sub-lineage of the SARS-CoV-2 Delta variant called AY.29, which has C5239T and T5514C mutations. We investigated the monthly trend of AY.29 in Japan within 37,737 Delta variants downloaded on October 2, 2021. Among the total Japanese Delta variants, the AY.29 sub-lineage accounted for 95.1%. In terms of monthly trends, the sequences became predominant in June, and accounted for 95.4%, 97.6% and 90.5% of the reported sequences in July, August and September, respectively. Furthermore, the number of Delta variants imported from abroad during the Tokyo 2020 Olympics and Paralympics (held in August 2021) was extremely low during the fifth wave in Japan. Therefore, the epidemic of the new Delta variant is attributable to a newly occurring mutation in Japan.

  🖺 Full Text HTML: Genomic Surveillance in Japan of AY.29—A New Sub-lineage of SARS-CoV-2 Delta Variant with C5239T and T5514C Mutations
• The COVID States Project #64: Continued high public support for mandating vaccines -
  COVID-19 continues to surge in the United States and elsewhere, propelled by the highly contagious Delta variant. As of this writing (on September 29, 2021), about three quarters (76%) of the eligible U.S. population (age 12 and up) have received at least one dose of a COVID-19 vaccine. This is likely not enough to achieve herd immunity in the United States. Though the specific number remains uncertain, a recent estimate by the Infectious Diseases Society of America suggests that over 80% of the entire population must be fully vaccinated to reach herd immunity. More worrisome, around 1 in 5 Americans, depending on the poll, continue to say they are either uncertain or will not get the vaccine. In our most recent survey wave (fielded from August 26 to September 27, 2021), 10% of respondents who indicated that they are not yet vaccinated claimed they are extremely unlikely to get it. Another 12% are “somewhat” unlikely to seek the vaccine. In recent weeks, the Biden administration has shifted tactics in its efforts to get as many Americans as possible vaccinated. The Administration had from the outset emphasized the benefits of getting vaccinated as its primary strategy for persuading reluctant Americans to do so. Yet, starting in September the prevailing strategy seemingly shifted from emphasizing carrots to sticks. On September 9th, President Biden issued an executive order requiring all federal employees and government contractors to be vaccinated, and also announced that the U.S. Department of Labor would require that all companies with more than 100 employees require vaccination or weekly testing, as well as provide paid time off for employees to get vaccinated. The Biden Administration has also encouraged states and smaller companies to impose similar vaccine mandates. The question arises as to whether the persistence of the Delta variant has increased public support for making COVID-19 vaccines mandatory. In our April/May survey wave, six in ten respondents approved of the government mandating vaccines for everyone (see Report #52). This figure increased modestly, to 64% in our June/July survey (see Report #58). In this report, we update our assessment of public support for vaccine mandates, both nationally and across the 50 states, based on our September survey wave.
  🖺 Full Text HTML: The COVID States Project #64: Continued high public support for mandating vaccines
• Giving a Socially Distanced Voice to Disabled Young People: Insights from the Educational Pathways and Work Outcomes Qualitative Longitudinal Study -
  The COVID-19 pandemic has created unprecedented challenges for social research. However, little is known about the impact of social distancing measures on research with hard-to-reach populations. This paper provides a methodological reflection on the efficiency of socially distanced recruitment and interviewing methods for research with disabled young people, drawing on our experience from the Educational Pathways and Work Outcomes longitudinal study, which started in November 2020 during the second national lockdown in England. We discuss difficulties in gaining access to disabled young people and argue that the pandemic has exacerbated longstanding barriers implicated in the recruitment of hard-to- reach populations who are typically seen as vulnerable by gatekeepers. In contrast, our experience suggests that flexible online/virtual interviews can overcome pitfalls inherent in the face-to-face interviewing of disabled young people and could therefore be utilised to make their voices heard in a variety of contexts and scenarios beyond the ongoing pandemic.
  🖺 Full Text HTML: Giving a Socially Distanced Voice to Disabled Young People: Insights from the Educational Pathways and Work Outcomes Qualitative Longitudinal Study
• High-throughput Activity Assay for Screening Inhibitors of the SARS-CoV-2 Mac1 Macrodomain -
  Macrodomains are a class of conserved ADP-ribosylhydrolases expressed by viruses of pandemic concern, including coronaviruses and alphaviruses. Viral macrodomains are critical for replication and virus-induced pathogenesis; therefore, these enzymes are a promising target for antiviral therapy. However, no potent or selective viral macrodo- main inhibitors currently exist, in part due to the lack of a high-throughput assay for this class of enzymes. Here, we developed a high-throughput ADP-ribosylhydrolase assay using the SARS-CoV-2 macrodomain Mac1. We performed a pilot screen which identified dasatinib and dihydralazine as ADP-ribosylhydrolase inhibitors. Importantly, dasatinib does not inhibit MacroD2, the closest Mac1 homolog in humans. Our study demonstrates the feasibility of identifying selective inhibitors based on ADP-ribosylhydrolase activity, paving the way for screening large compound libraries to identify improved macrodomain inhibitors and explore their potential as antiviral therapies for SARS-CoV-2 and future viral threats.
  🖺 Full Text HTML: High-throughput Activity Assay for Screening Inhibitors of the SARS-CoV-2 Mac1 Macrodomain

From Clinical Trials

• Prophylaxis of COVID-19 Disease With Ivermectin in COVID-19 Contact Persons [German: Prophylaxe Der COVID-19-Erkrankung Mit Ivermectin Bei COVID-19 Kontaktpersonen] - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Drug: Placebo
  Sponsors:  
  Infectopharm Arzneimittel GmbH;   GKM Gesellschaft für Therapieforschung mbH
  Not yet recruiting

• Evaluating Safety, Tolerability, and Potential Efficacy of Intranasal AD17002 in Adults With Mild COVID-19 - Condition:   Covid19
  Interventions:   Biological: AD17002;   Biological: Placebo (Formulation buffer)
  Sponsor:   Advagene Biopharma Co. Ltd.
  Not yet recruiting

• Lymphatic Osteopathic Manipulative Medicine to Enhance Coronavirus (COVID-19) Vaccination Efficacy - Condition:   COVID-19
  Interventions:   Other: Lymphatic OMM;   Other: Light Touch
  Sponsor:   Rowan University
  Not yet recruiting

• A Study of AZD1222, a Vaccine for the Prevention of COVID-19 in Immunocompromised Adults - Condition:   COVID-19, SARS-CoV-2
  Intervention:   Biological: AZD1222
  Sponsor:  
  AstraZeneca
  Not yet recruiting

• “Efesovir” (FS-1) for COVID-19, Phase 2 - Condition:   Covid19
  Intervention:   Drug: Efesovir
  Sponsor:   Scientific Center for Anti-infectious Drugs, Kazakhstan
  Not yet recruiting

• SARS-CoV-2 Infection in COVID-19 Vaccinated Patients - Condition:   COVID-19
  Intervention:   Diagnostic Test: COVID-19 vaccinated people
  Sponsor:   Hospices Civils de Lyon
  Recruiting

• The Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores - Condition:   COVID-19 Pneumonia
  Intervention:   Biological: Bacillus subtilis
  Sponsor:   DreamTec Research Limited
  Recruiting

• Phase I/II of the Safety and Immunogenicity of SARS-CoV-2 Protein Subunit Recombinant Vaccine in Healthy Populations - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 Protein Subunit Recombinant Vaccine;   Biological: SARS-CoV-2 Inactivated Vaccine
  Sponsors:   PT Bio Farma;   Fakultas Kedokteran Universitas Indonesia;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
  Not yet recruiting

• A Ph 2 Trial With an Oral Tableted COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Drug: VXA-CoV2-1.1-S;   Other: Placebo Tablets
  Sponsor:   Vaxart
  Recruiting

• Randomized Trial of COVID-19 Booster Vaccinations (Cobovax Study) - Condition:   COVID-19 Vaccination
  Interventions:   Biological: BNT162b2;   Biological: CoronaVac
  Sponsor:   The University of Hong Kong
  Not yet recruiting

• RCT on the Efficacy of Dexamethasone Versus Methyl Prednisolone in Covid-19 Infected Patients With High Oxygen Flow - Condition:   COVID-19 Pandemic
  Interventions:   Drug: Dexamethasone;   Drug: Methylprednisolone
  Sponsor:   Cairo University
  Recruiting

• Third Dose of mRNA Vaccination to Boost COVID-19 Immunity - Condition:   COVID 19 Vaccine
  Intervention:   Biological: BNT162b2
  Sponsor:  
  The University of Hong Kong
  Recruiting

• Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above - Conditions:   COVID-19 Pneumonia;   Coronavirus Infections
  Interventions:   Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08);   Biological: COVID-19 vaccine (Vero cells);   Biological: 3 doses Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)
  Sponsors:   National Vaccine and Serum Institute, China;   China National Biotec Group Company Limited;   Lanzhou Institute of Biological Products Co., Ltd
  Not yet recruiting

• Safety, Tolerability and Efficacy of Uproleselan (GMI-1271) in Patients With COVID-19 Pneumonia - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Uproleselan
  Sponsors:  
  Lena Napolitano, MD;   GlycoMimetics Incorporated
  Not yet recruiting

• EFFECTIVENESS, SAFETY AND IMMUNOGENICITY OF THE HALF DOSE OF THE VACCINE ChadOx1 nCoV-19 (AZD1222) for COVID-19 - Condition:   SARS-CoV-2
  Interventions:   Biological: Half dose of ChAdOx1 nCoV-19 (AZD1222);   Biological: Standard dose of ChAdOx1 nCoV-19 (AZD1222)
  Sponsors:   Federal University of Espirito Santo;   Instituto René Rachou/Fiocruz;   Escola Nacional de Saúde Pública Sérgio Arouca/Fiocruz;   Programa de Computação Científica/Fiocruz;   Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória
  Recruiting

From PubMed

• Early IgG / IgA response in hospitalized COVID-19 patients is associated with a less severe disease - We determined the kinetics of anti-SARS-CoV-2 antibody response in fifteen hospitalized COVID-19 patients. Patients were divided into mild/moderate (mild, n = 1; moderate, n = 4) or severe (n = 10) and virus-specific anti-Nucleocapsid IgM, anti-Spike IgG and anti-Spike IgA were measured in serial serum samples collected 0 to 15 days after hospital admission. Surrogate neutralization assays were performed by testing inhibition of ACE-2 binding to Spike. In 3 patients (2 severe and 1 moderate…

• Role of miR-2392 in driving SARS-CoV-2 infection - MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene…

• The N-terminal domain of SARS-CoV-2 nsp1 plays key roles in suppression of cellular gene expression and preservation of viral gene expression - Nonstructural protein 1 (nsp1) is a coronavirus (CoV) virulence factor that restricts cellular gene expression by inhibiting translation through blocking the mRNA entry channel of the 40S ribosomal subunit and by promoting mRNA degradation. We perform a detailed structure-guided mutational analysis of severe acute respiratory syndrome (SARS)-CoV-2 nsp1, revealing insights into how it coordinates these activities against host but not viral mRNA. We find that residues in the N-terminal and central…

• The Repurposed ACE2 Inhibitors: SARS-CoV-2 Entry Blockers of Covid-19 - The highly infectious disease COVID-19 is induced by SARS-coronavirus 2 (SARS-CoV-2), which has spread rapidly around the globe and was announced as a pandemic by the World Health Organization (WHO) in March 2020. SARS-CoV-2 binds to the host cell’s angiotensin converting enzyme 2 (ACE2) receptor through the viral surface spike glycoprotein (S-protein). ACE2 is expressed in the oral mucosa and can therefore constitute an essential route for entry of SARS-CoV-2 into hosts through the tongue and…

• Conflicting impacts of tocilizumab and colchicine in COVID-19-associated coagulop - Severely affected COVID-19 patients may develop a delayed onset “cytokine storm”, which includes an increase in interleukin-6 (IL-6). This may be followed by a pro-thrombotic state and increased D-dimer. It has been anticipated that tocilizumab (TCZ), an anti-IL-6 receptor, would mitigate inflammation and coagulation in COVID-19 patients. However, clinical trials with TCZ recorded an increase in D-dimer. In contrast to TCZ, colchicine reduced D-dimer COVID-19 patients. To understand how the two…

• Viral polymerase binding and broad-spectrum antiviral activity of molnupiravir against human seasonal coronaviruses - Endemic seasonal coronaviruses cause morbidity and mortality in a subset of patients, but no specific treatment is available. Molnupiravir is a promising pipeline antiviral drug for treating SARS-CoV-2 infection potentially by targeting RNA-dependent RNA polymerase (RdRp). This study aims to evaluate the potential of repurposing molnupiravir for treating seasonal human coronavirus (HCoV) infections. Molecular docking revealed that the active form of molnupiravir, β-D-N⁴-hydroxycytidine (NHC),…

• Dissolving microneedle patches loaded with amphotericin B microparticles for localised and sustained intradermal delivery: Potential for enhanced treatment of cutaneous fungal infections - Fungal infections affect millions of people globally and are often unreceptive to conventional topical or oral preparations because of low drug bioavailability at the infection site, lack of sustained therapeutic effect, and the development of drug resistance. Amphotericin B (AmB) is one of the most potent antifungal agents. It is increasingly important since fungal co-infections associated with COVID-19 are frequently reported. AmB is only administered via injections (IV) and restricted to…

• Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective - The absence of ‘shovel-ready’ anti-coronavirus drugs during vaccine development has exceedingly worsened the SARS-CoV-2 pandemic. Furthermore, new vaccine-resistant variants and coronavirus outbreaks may occur in the near future, and we must be ready to face this possibility. However, efficient antiviral drugs are still lacking to this day, due to our poor understanding of the mode of incorporation and mechanism of action of nucleotides analogs that target the coronavirus polymerase to impair…

• Inhaled [D-Ala(2)]-Dynorphin 1-6 Prevents Hyperacetylation and Release of High Mobility Group Box 1 in a Mouse Model of Acute Lung Injury - COVID-19 is a respiratory infection caused by the SARS-CoV-2 virus that can rapidly escalate to life-threatening pneumonia and acute respiratory distress syndrome (ARDS). Recently, extracellular high mobility group box 1 (HMGB1) has been identified as an essential component of cytokine storms that occur with COVID-19; HMGB1 levels correlate significantly with disease severity. Thus, the modulation of HMGB1 release may be vital for treating COVID-19. HMGB1 is a ubiquitous nuclear DNA-binding…

• COVID-19 and the global need for knowledge on nurses’ health - CONCLUSIONS: These issues are reflected in the limited capacity of many national public health information systems to collect, monitor and report on the health of the largest group of health workers. Political will, accountability and public data transparency at different levels are essential to adequately protect nurses at work.

• Highly efficient SARS-CoV-2 infection of human cardiomyocytes: spike protein-mediated cell fusion and its inhibition - Severe cardiovascular complications can occur in coronavirus disease of 2019 (COVID-19) patients. Cardiac damage is attributed mostly to the aberrant host response to acute respiratory infection. However, direct infection of cardiac tissue by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also occurs. We examined here the cardiac tropism of SARS-CoV-2 in spontaneously beating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). These cardiomyocytes express the…

• Reductionism Ad Absurdum: The Misadventures of Structural Biology in the Time of Coronavirus - The tragic consequences of the COVID-19 pandemic have led to admirable responses by the global scientific community, including a profound acceleration in the pace of research and exchange of findings. However, this has had considerable costs of its own, as erroneous conclusions have propagated faster than researchers have been able to detect and correct them. We illustrate the specific misunderstandings that have resulted from reductionist approaches to the study of SARS- CoV-2 RNA-dependent RNA…

• Antiviral effects of human placenta hydrolysate (Laennec()) against SARS-CoV-2 in vitro and in the ferret model - The COVID-19 pandemic has caused unprecedented health, social, and economic crises worldwide. However, to date, there is an only a limited effective treatment for this disease. Human placenta hydrolysate (hPH) has previously been shown to be safe and to improve the health condition in patients with hyperferritinemia and COVID-19. In this study, we aimed to determine the antiviral effects of hPH against SARS-CoV-2 in vitro and in vivo models and compared with Remdesivir, an FDA-approved drug for…

• PABPC4 Broadly Inhibits Coronavirus Replication by Degrading Nucleocapsid Protein through Selective Autophagy - Emerging coronaviruses (CoVs) can cause severe diseases in humans and animals, and, as of yet, none of the currently available broad-spectrum drugs or vaccines can effectively control these diseases. Host antiviral proteins play an important role in inhibiting viral proliferation. One of the isoforms of cytoplasmic poly(A)-binding protein (PABP), PABPC4, is an RNA-processing protein, which plays an important role in promoting gene expression by enhancing translation and mRNA stability. However,…

• The key role of the central cavity in sodium transport through ligand-gated two-pore channels - Subcellular and organellar mechanisms have manifested a prominent importance for a broad variety of processes that maintain cellular life at its most basic level. Mammalian two-pore channels (TPCs) appear to be cornerstones of these processes in endo-lysosomes by controlling delicate ion-concentrations in their interiors. With evolutionary remarkable architecture and one-of-a-kind selectivity filter, TPCs are an extremely attractive topic per se. In the light of the current COVID-19 pandemic,…

From Patent Search

• 스몰 RNA 검출 방법 - 본 발명은 스몰(small) RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 짧은 염기서열의 RNA까지 분석이 가능하면서도 높은 민감도 및 정확도로 정량적 검출까지 가능하여 감염증, 암 등 여러 질환의 진단 용도로도 널리 활용될 수 있다. - link

• 健康智能检测方法、装置、电子设备及可读存储介质 - 本申请公开了一种健康智能检测方法、装置、电子设备及可读存储介质，其方法包括获取音频信号，并对所述音频信号进行预处理，得到检测信号；将所述检测信号转化为矩阵数字矩阵；将得到的矩阵数字矩阵作为检测样本，输入健康智能检测模型中，以获取检测结果；其中，所述健康智能检测模型是采用迁移学习和卷积神经网络对训练样本进行训练得到的。本申请由于卷积神经网络各组件或部分组件基于迁移学习进行了重新训练，显著提升了对人们健康检测的准确度；且本申请中的健康智能检测模型为分类模型，计算量小，可将其部署于人们的移动终端中，使用方便，极大程度上提升了用户的使用感受。 - link

• MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS - - link

• 单克隆抗体32C7及其制备方法和用途 - 本发明公开了单克隆抗体32C7及其制备方法和用途。本发明通过制备针对于新冠病毒RBD结构域的中和抗体32C7，在体外通过表面等离子共振检测抗体32C7可以有效地与新冠病毒的S蛋白的RBD结构域结合，通过转基因小鼠感染模型验证了抗体32C7的中和能力，测定了中和抗体32C7对于新冠感染后的肺部病毒滴度和相关炎症因子的抑制效果，结果显示该中和抗体能够明显的抑制病毒在体内的复制并降低炎症因子的产生和肺部炎症浸润。单克隆中和抗体32C7抑制新冠病毒的进入宿主细胞，达到新冠病毒中和抗体的治疗作用，可有效用于治疗或者预防新冠病毒感染引起的呼吸系统损伤。 - link

• 单克隆抗体35B5及其制备方法和用途 - 本发明公开了单克隆抗体35B5及其制备方法和用途。本发明通过制备针对于新冠病毒RBD结构域的中和抗体35B5，在体外通过表面等离子共振检测抗体35B5可以有效地与新冠病毒的S蛋白的RBD结构域结合，通过转基因小鼠感染模型验证了抗体35B5的中和能力，测定了中和抗体35B5对于新冠感染后的肺部病毒滴度和相关炎症因子的抑制效果，结果显示该中和抗体能够明显的抑制病毒在体内的复制并降低炎症因子的产生和肺部炎症浸润。单克隆中和抗体35B5抑制新冠病毒的进入宿主细胞，达到新冠病毒中和抗体的治疗作用，可有效用于治疗或者预防新冠病毒感染引起的呼吸系统损伤。 - link

• A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link

• 治疗或预防新冠病毒的靶点 - 本发明提供一种蛋白片段，是如下至少一种：A1)氨基酸酸序列如SEQ ID NO.1所示；A2）氨基酸序列如SEQ ID NO.1第12位‑34位所示；A3）将A1)的蛋白片段的第18、19、28和29位中的任意一个或几个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A1)所示的蛋白片段具有90％以上的同一性的蛋白片段；A4）氨基酸酸序列如SEQ ID NO.2所示；A5）氨基酸序列如SEQ ID NO.2第32‑41位所示；A6）将A4)的蛋白片段的第35和36位中的任意1个或2个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A4)所示的蛋白片段具有90％以上的同一性的蛋白片段。 - link

• 一种抗病毒化合物及其制备方法 - 本发明公开了一种抗病毒的化合物及其制备方法。该化合物的结构式如式I所示，式(Ⅰ)中，R1选自：单取代或多取代的H、F、甲基、三氟甲基；R2选自：H、直链或取代烷烃(C1‑C6)；R3选自：单取代或多取代的H、Cl、Br、F。本发明中所述化合物经过实验证实，不仅对于H1N1甲型流感病毒具有较好的抑制作用，并且对于冠状病毒也具有较好的抑制作用，没有观察到对于人正常细胞的毒性，且能够在抗病毒的同时抑制炎症反应的程度。 - link

• 以痘苗病毒为载体的新冠疫苗 - 本申请涉及一种基于经过基因工程改造的痘苗病毒为载体的新型冠状病毒南非突变株疫苗。所述疫苗以A46R缺陷的痘苗病毒为载体携带新冠病毒南非突变株S基因核酸序列，所述痘苗病毒载体还可以携带IL‑21，该疫苗在免疫小鼠后可以产生针对新冠病毒南非突变株的抗体。 - link

• 氧化钛负载银单原子的材料在病毒消杀中的应用 - 本发明属于生物医药领域，尤其涉及一种负载银单原子的材料在病毒消杀中的应用，所述氧化钛负载银单原子材料具有以下的结构：银单原子以单分散的形式，稳定地锚定于氧化钛的表面和/或骨架中，键合方式为Ti‑O‑Ag；银单原子的嵌合使Ag单原子和氧化钛的电子结构带隙范围为2.9‑3.2

eV；氧化钛负载银单原子材料具有较银纳米颗粒更加优异的催化活性，具有过氧化物酶活性，利用羟基自由基可高效破坏核酸和蛋白质的原理来实现广谱消杀病毒，银单原子的嵌合使Ag单原子和氧化钛的电子结构带隙变小，对可见光的敏感性更强，可将光照射下的光催化诱导光动力杀伤病毒。 - link