Covid-19 Sentry

Contents

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

From Preprints

• SARS-CoV-2 mechanisms of action and impact on human organism, risk factors and potential treatments. An exhaustive survey. -
  Novel COVID-19 is the most considerable health threat the humanity has faced in decades, with global impact also in the social and economic scopes. Moreover, SARS-CoV-2 involves an unprecedented exciting scientific challenge that has focused all efforts on defeating the new coronavirus. Research results are continuously increasing and updating knowledge about the virus and the disease, and understanding the virus characteristics is essential in order to identify and attack its weak points, as well as uncovering the host reactions to search for treatments. Through this survey we will offer the reader a thorough exposition on how SARS-CoV-2 infects and affects the organism, the wide set of risk factors that impact the course of the disease, related biomarkers, and potential drugs and treatments against the virus host entry and the consequences of the infection.
  🖺 Full Text HTML: SARS-CoV-2 mechanisms of action and impact on human organism, risk factors and potential treatments. An exhaustive survey.
• Identifiability as an “Antidote”: Exploring Emotional Contagion and the Role of Anonymity in Twitter Discussions on Misinformation -
  Misinformation carries both distorted facts and sophisticated emotional signals. Comparing to facts that could be labeled as true or false, we are more concerned about contaminative negative emotions transferring digital-ly among users. In this study, we explored an emotional contagion effect among misinformation discussion participants on Twitter. We analyzed the sentiment of 573 tweets in 192 discussion threads. Our result revealed that highly emotional tweets do not have a universal effect on the online discussions, but it affects those individuals with limited social and personal identity cues (i.e., being anonymous). We found that anonymous members of the online discussion are more susceptible to emotional contagions than those are not. We also suggest coping strategies that protect social media users’ emotional well-being during the era COVID-19.
  🖺 Full Text HTML: Identifiability as an “Antidote”: Exploring Emotional Contagion and the Role of Anonymity in Twitter Discussions on Misinformation
• The Host Interactome of Spike Expands the Tropism of SARS-CoV-2 -
  The SARS-CoV-2 virus causes severe acute respiratory syndrome (COVID-19) and has rapidly created a global pandemic. Patients that survive may face a slow recovery with long lasting side effects that can afflict different organs. SARS-CoV-2 primarily infects epithelial airway cells that express the host entry receptor Angiotensin Converting Enzyme 2 (ACE2) which binds to spike protein trimers on the surface of SARS-CoV-2 virions. However, SARS-CoV-2 can spread to other tissues even though they are negative for ACE2. To gain insight into the molecular constituents that might influence SARS-CoV-2 tropism, we determined which additional host factors engage with the viral spike protein in disease-relevant human bronchial epithelial cells (16HBEo-). We found that spike recruited the extracellular proteins laminin and thrombospondin and was retained in the endoplasmatic reticulum (ER) by the proteins DJB11 and FBX2 which support re-folding or degradation of nascent proteins in the ER. Because emerging mutations of the spike protein potentially impact the virus tropism, we compared the interactome of D614 spike with that of the rapidly spreading G614 mutated spike. More D614 than G614 spike associated with the proteins UGGT1, calnexin, HSP7A and GRP78/BiP which ensure glycosylation and folding of proteins in the ER. In contrast to G614 spike, D614 spike was endoproteolytically cleaved, and the N-terminal S1 domain was degraded in the ER even though C-terminal S2-only proteoforms remained present. D614 spike also bound more laminin than G614 spike, which suggested that extracellular laminins may function as co-factors for an alternative, S2-only dependent virus entry. Because the host interactome determines whether an infection is productive, we developed a novel proteome-based cell type set enrichment analysis (pCtSEA). With pCtSEA we determined that the host interactome of the spike protein may extend the tropism of SARS-CoV-2 beyond mucous epithelia to several different cell types, including macrophages and epithelial cells in the nephron. An S2-only dependent, alternative infection of additional cell types with SARS-CoV-2 may impact vaccination strategies and may provide a molecular explanation for a severe or prolonged progression of disease in select COVID-19 patients.
  🖺 Full Text HTML: The Host Interactome of Spike Expands the Tropism of SARS-CoV-2
• Single-Domain SARS-CoV-2 S1 and RBD Antibodies Isolated from Immunized Llama Effectively Bind Targets of the Wuhan, UK, and South African Strains in vitro -
  The spreading of SARS-CoV-2 variants has become a major challenge of the current fight against the pandemic. Of particular concerns are the strains that have arisen from the United Kingdom (UK) and South Africa. The UK variant spreads rapidly and is projected to overtake the original strain in the US as early as in March 2021, while the South African variant appears to evade some effects of the current vaccines. Potential false-negative diagnosis using currently available antigen kits that may not recognize these variants could cause another wave of community infection. Therefore, it is imperative that antibodies used in the detection kits are validated for binding against these variants. Here we report that the nanoantibodies (nAbs in our terminology, also referred to as VHH fragments, single domain antibodies, nanobodiesTM) that we have developed for rapid antigen detection test bind the receptor binding domain (RBD) of the S1 protein from the original COVID-SARS-2 virus as well as those from the UK and South African variants. This finding validates our antibodies used in our assay for the detection of these major variant strains.
  🖺 Full Text HTML: Single-Domain SARS-CoV-2 S1 and RBD Antibodies Isolated from Immunized Llama Effectively Bind Targets of the Wuhan, UK, and South African Strains in vitro
• Identification of common key genes and pathways between Covid-19 and lung cancer by using protein-protein interaction network analysis -
  COVID-19 is indeed an infection that is caused by a recently found coronavirus group, a type of virus proven to cause human respiratory diseases. The high mortality rate was observed in patients who had pre-existing health conditions like cancer. However, the molecular mechanism of SARS-CoV-2 infection in lung cancer patients was not discovered yet at the pathway level. This study was about determining the common key genes of COVID-19 and lung cancer through network analysis. The hub genes associated with COVID-19 and lung cancer were identified through Protein-Protein interaction analysis. The hub genes are ALB, CXCL8, FGF2, IL6, INS, MMP2, MMP9, PTGS2, STAT3 and VEGFA. Through gene enrichment, it is identified both COVID-19 and lung cancer have a common pathway in EGFR tyrosine kinase inhibitor resistance, IL-17 signalling pathway, AGE-RAGE signalling pathway in diabetic complications, HIF-1 signalling pathway and pathways in cancer.
  🖺 Full Text HTML: Identification of common key genes and pathways between Covid-19 and lung cancer by using protein-protein interaction network analysis
• Live attenuated SARS-CoV-2 vaccine candidate: Protective immunity without serious lung lesions in Syrian hamsters -
  Various COVID-19 vaccine candidates are currently under clinical trial. However, no live attenuated vaccine has been developed yet, despite their generally high efficacy. Here, we established temperature-sensitive mutant strains of SARS-CoV-2, whose growth was significantly slower than that of the parent strain at 37{ring}C. One of the strains, A50-18, which presented mutations in nonstructural protein 14, did not replicate at all at 37{ring}C in vitro. In vivo experiments demonstrated that this strain replicated inefficiently in the lungs of Syrian hamsters, and intra-nasal inoculation induced sufficient anti-SARS-CoV-2-neutralizing antibodies to protect against wild type virus infection. These results suggest that the A50-18 strain could be a promising live attenuated vaccine candidate against SARS-CoV-2.
  🖺 Full Text HTML: Live attenuated SARS-CoV-2 vaccine candidate: Protective immunity without serious lung lesions in Syrian hamsters
• Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV -
  There is an urgent need to understand the nature of immune responses generated against SARS-CoV-2, to better inform risk-mitigation strategies for people living with HIV (PLWH). Although not all PLWH are considered immunosuppressed, residual cellular immune deficiency and ongoing inflammation could influence COVID-19 disease severity, the evolution and durability of protective memory responses. Here, we performed an integrated analysis, characterizing the nature, breadth and magnitude of SARS-CoV-2-specific immune responses in PLWH, controlled on ART, and HIV negative subjects. Both groups were in the convalescent phase of predominately mild COVID-19 disease. The majority of PLWH mounted SARS-CoV-2 Spike- and Nucleoprotein-specific antibodies with neutralizing activity and SARS-CoV-2-specific T cell responses, as measured by ELISpot, at levels comparable to HIV negative subjects. T cell responses against Spike, Membrane and Nucleocapsid were the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. Notably, the overall magnitude of SARS-CoV-2-specific T cell responses related to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH, in whom disparate antibody and T cell responses were observed. Both humoral and cellular responses to SARS-CoV-2 were detected at 5-7 months post-infection, providing evidence of medium-term durability of responses irrespective of HIV serostatus. Incomplete immune reconstitution on ART and a low CD4:CD8 ratio could, however, hamper the development of immunity to SARS-CoV-2 and serve as a useful tool for risk stratification of PLWH. These findings have implications for the individual management and potential effectiveness of vaccination against SARS-CoV-2 in PLWH.
  🖺 Full Text HTML: Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV
• Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases -
  Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction or suppression unknown. Here, we examined the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. Despite immune dysfunction and immunosuppressive treatment, JIA, JDM and JSLE patients mounted comparable or stronger responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM and JSLE patients, arguing against increased exposure. Consequently, autoimmune rheumatic diseases and their treatment were associated with a favourable ratio of spike to nucleoprotein antibodies.
  🖺 Full Text HTML: Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases
• A chicken IgY can efficiently inhibit the entry and replication of SARS-CoV-2 by targeting the ACE2 binding domain in vitro -
  COVID-19 pneumonia is spreading widely in the world now. Currently, no specific antiviral drugs have been developed. The vaccine is the most effective way to control the epidemic. Passive immune antibodies are also an effective method to prevent and cure COVID-19 pneumonia. We used SARS-CoV-2 S-RBD as an antigen to immunize layers in order to extract, separate and purify SARS-CoV-2-IgY from egg yolk. SARS-CoV-2-IgY(S-IgY) can block the entry of SARS-CoV-2 into the Cells and reduce the viral load in cells. The EC50 of W3-IgY (S-IgY in the third week after immunization) is 1.35 {+/-} 0.15 nM. The EC50 of W9-IgY (S-IgY in the ninth week after immunization) is 2.76 {+/-} 1.54 nM. When the dose of S-IgY is 55 nM, the fluorescence representing intracellular viral protein is obviously weakenedin Immunofluorescence microscopy. Results of Sars-CoV-2/VeroE6 cell experiment confirmed that S-IgY had strong antiviral effecton SARS-Co-V-2, and its EC50 is 27.78 {+/-} 1.54nM vs 3259 {+/-} 159.62 nM of Redesivir (differ>106 times, P<0.001 ). S-IgY can inhibit the entry and replication of SARS-CoV-2, which is related to its targeting the ACE2 binding domain. S-IgY is safe, efficient, stable and easy to obtain. This antibody may have the potential to be an effective method for the prevention and treatment of COVID-19 pneumonia.
  🖺 Full Text HTML: A chicken IgY can efficiently inhibit the entry and replication of SARS-CoV-2 by targeting the ACE2 binding domain in vitro
• A glycan gate controls opening of the SARS-CoV-2 spike protein -
  SARS-CoV-2 infection is controlled by the opening of the spike protein receptor binding domain (RBD), which transitions from a glycan-shielded (down) to an exposed (up) state in order to bind the human ACE2 receptor and infect cells. While snapshots of the up and down states have been obtained by cryoEM and cryoET, details of the RBD opening transition evade experimental characterization. Here, over 200 s of weighted ensemble (WE) simulations of the fully glycosylated spike ectodomain allow us to characterize more than 300 continuous, kinetically unbiased RBD opening pathways. Together with biolayer interferometry experiments, we reveal a gating role for the N-glycan at position N343, which facilitates RBD opening. Residues D405, R408, and D427 also participate. The atomic-level characterization of the glycosylated spike activation mechanism provided herein achieves a new high-water mark for ensemble pathway simulations and offers a foundation for understanding the fundamental mechanisms of SARS-CoV-2 viral entry and infection.
  🖺 Full Text HTML: A glycan gate controls opening of the SARS-CoV-2 spike protein
• Transfer learning via multi-scale convolutional neural layers for human-virus protein-protein interaction prediction -
  To predict interactions between human and viral proteins, we combine evolutionary sequence profile features with a Siamese convolutional neural network (CNN) architecture and a multi-layer perceptron (MLP). Our architecture outperforms various feature encodings-based machine learning and state-of-the-art prediction methods. As our main contribution, we introduce two types of transfer learning methods (i.e., frozen type and fine-tuning type) that reliably predict interactions in a target human-virus domain based on training in a source human-virus domain, by retraining CNN layers. Our transfer learning strategies can effectively apply prior knowledge transfer from large source dataset/task to small target dataset/task to improve prediction performance. Finally, we utilize the frozen type of transfer learning to predict human-SARS-CoV-2 PPIs, indicating that our predictions are topologically and functionally similar to experimentally known interactions.
  🖺 Full Text HTML: Transfer learning via multi-scale convolutional neural layers for human-virus protein-protein interaction prediction
• Timeline of the Works on the Correlation between COVID-19 and Y-DNA Haplogroup R1b -
  Soon after the beginning of COVID-19 pandemic, many works have been reporting a yet-to-be-explained correlation of COVID-19 prevalence and severity with Y-DNA haplogroup R1b frequency. Here a chronologically ordered list of such works is provided.
  🖺 Full Text HTML: Timeline of the Works on the Correlation between COVID-19 and Y-DNA Haplogroup R1b
• What is essential travel? Socio-economic differences in travel demand during the COVID-19 lockdown -
  The COVID-19 pandemic has profoundly reshaped urban mobility. During the lockdown, workers teleworked if possible and left home only for essential activities. Our study investigates the spatial patterns of essential travel and their socio-economic differences during the COVID-19 lockdown phase in comparison with the same period in 2019. Using data from Columbus, Ohio, we categorized travelers into high, moderate, and low socio-economic status (SES) clusters and modeled travel demand of SES clusters for both phases using spatially weighted interaction models. Then, we characterized the SES variability in essential travel based on frequently visited business activities from each cluster. Results suggest that disparities in travel across SES clusters existed prior to COVID-19 are exacerbated during the pandemic lockdown. The diffused travel pattern of high and moderate SES cluster became localized while the pre-existing localized travel pattern of low SES cluster became diffused. During the lockdown, the low and moderate SES clusters travelled mostly for work with long and medium distance trips, respectively, while the high SES cluster travelled mostly for recreational and other non-work purposes with short distance trips. This study draws some conclusions and implications to help researchers and practitioners plan for resilient and economically vibrant transportation systems in response to future shocks.
  🖺 Full Text HTML: What is essential travel? Socio-economic differences in travel demand during the COVID-19 lockdown
• Prioritizing allocation of COVID-19 vaccines based on social contacts increases vaccination effectiveness -

  We study allocation of COVID-19 vaccines to individuals based on the structural properties of their underlying social contact network. Even optimistic estimates suggest that most countries will likely take 6 to 24 months to vaccinate their citizens. These time estimates and the emergence of new viral strains urge us to find quick and effective ways to allocate the vaccines and contain the pandemic. While current approaches use combinations of age-based and occupation-based prioritizations, our strategy marks a departure from such largely aggregate vaccine allocation strategies. We propose a novel approach motivated by recent advances in (i) science of real-world networks that point to efficacy of certain vaccination strategies and (ii) digital technologies that improve our ability to estimate some of these structural properties. Using a realistic representation of a social contact network for the Commonwealth of Virginia, combined with accurate surveillance data on spatiotemporal cases and currently accepted models of within- and between-host disease dynamics, we study how a limited number of vaccine doses can be strategically distributed to individuals to reduce the overall burden of the pandemic. We show that allocation of vaccines based on individuals9 degree (number of social contacts) and total social proximity time is significantly more effective than the currently used age-based allocation strategy in terms of number of infections, hospitalizations and deaths. Our results suggest that in just two months, by March 31, 2021, compared to age-based allocation, the proposed degree-based strategy can result in reducing an additional 56−110k infections, 3.2− 5.4k hospitalizations, and 700−900 deaths just in the Commonwealth of Virginia. Extrapolating these results for the entire US, this strategy can lead to 3−6 million fewer infections, 181−306k fewer hospitalizations, and 51−62k fewer deaths compared to age-based allocation. The overall strategy is robust even: (i) if the social contacts are not estimated correctly; (ii) if the vaccine efficacy is lower than expected or only a single dose is given; (iii) if there is a delay in vaccine production and deployment; and (iv) whether or not non-pharmaceutical interventions continue as vaccines are deployed. For reasons of implementability, we have used degree, which is a simple structural measure and can be easily estimated using several methods, including the digital technology available today. These results are significant, especially for resource-poor countries, where vaccines are less available, have lower efficacy, and are more slowly distributed.

  🖺 Full Text HTML: Prioritizing allocation of COVID-19 vaccines based on social contacts increases vaccination effectiveness
• Minimizing loss of life in Covid-19 in a 100 day period in the U.S.A. by personalized-dose vaccination and distribution of a limited vaccine supply -

  Background: We aimed at minimizing loss of lives in the Covid-19 pandemic in the USA by identifying optimal vaccination strategies during a 100-day period with limited vaccine supplies. While lethality is highest in the elderly, transmission and case numbers are highest in the younger. A strategy of first vaccinating the elderly is widely used, thought to protect the vulnerable, elderly best. Despite lower immunogenicity in the elderly, mRNA vaccines retain high efficacy, implying that in the younger, reduced vaccine doses might suffice, thereby increasing vaccination counts with a given vaccine supply. Methods: Using published immunogenicity data of the Moderna mRNA-1273 vaccine, we examined the value of tailored-dose vaccination strategies, using a modeling approach incorporating age-related vaccine immunogenicity, social contact patterns, population structure, Covid-19 case and death rates in the USA in late January 2021. An increase if the number of persons that can be vaccinated and a potential reduction of the individual protective efficacy was accounted for. Results: Age-tailored dosing strategies reduced cases faster, shortening the pandemic, reducing the delay to reaching <100′000 cases/day from 64 to 30 days and avoiding 25′000 deaths within 100 days in the USA. In an ′elderly first′ vaccination strategy, mortality is higher even in the elderly. Findings were robust with transmission blocking efficacies of reduced dose vaccination between 30% to 90%, and with a vaccine supply from 1 to 3 million full dose vaccinations per day. Conclusion: Rapid reduction of Covid-19 case and death rate in the USA in 100 days with a limited vaccine supply is best achieved when personalized, age-tailored dosing for highly effective vaccines is used. Protecting the vulnerable is most effectively achieved by dose tailored vaccination of all population segments, while an ′elderly first′ approach costs more lives, even in the elderly.

  🖺 Full Text HTML: Minimizing loss of life in Covid-19 in a 100 day period in the U.S.A. by personalized-dose vaccination and distribution of a limited vaccine supply

From Clinical Trials

• Study to Evaluate the Safety and Efficacy of a Single Dose of STI-2020 (COVI-AMG™) to Treat COVID-19 - Condition:   Covid19
  Interventions:   Biological: COVI-AMG;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• An Effectiveness Study of the Sinovac’s Adsorbed COVID-19 (Inactivated) Vaccine - Condition:   Covid19
  Intervention:   Biological: Adsorbed COVID-19 (Inactivated) Vaccine
  Sponsor:   Butantan Institute
  Enrolling by invitation

• Telerehabilitation in Covid-19 After Hospital Discharge - Condition:   Covid19
  Interventions:   Other: Standard Physiotherapy program;   Other: Telerehabilitation
  Sponsor:   Universidad de Granada
  Not yet recruiting

• Study of the Kinetics of COVID-19 Antibodies for 24 Months in Patients With Confirmed SARS-CoV-2 Infection - Conditions:   Covid19;   SARS-CoV 2
  Intervention:   Other: Sampling by venipuncture
  Sponsor:   Centre Hospitalier Régional d’Orléans
  Recruiting

• Effect of Prone Position onV/Q Matching in Non-intubated Patients With COVID-19 - Condition:   Covid19
  Intervention:   Other: prone position
  Sponsor:   Southeast University, China
  Not yet recruiting

• COVID-19 Convalescent Plasma Therapy - Conditions:   SARS-CoV-2 Infection;   COVID-19 Infection
  Intervention:   Biological: Convalescent plasma
  Sponsors:   Angelica Samudio;   Consejo Nacional de Ciencias y Tecnología, Paraguay;   Ministerio de Salud Pública y Bienestar Social, Paraguay;   Centro de información y recursos para el desarrollo, Paraguay
  Completed

• Oxidative Stress Parameters, Trace Element and Quality of Life in Women Before and After Covid-19 Vaccines - Condition:   Covid-19 Vaccine
  Intervention:   Biological: CoronoVac Vaccine
  Sponsors:   Izmir Bakircay University;   Cigli Regional Training Hospital;   Muğla Sıtkı Koçman University
  Not yet recruiting

• Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: Ivermectin
  Sponsor:   FMH College of Medicine and Dentistry
  Completed

• COVID 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

• AGILE (Early Phase Platform Trial for COVID-19) - Condition:   Covid19
  Interventions:   Drug: CST-2: EIDD-2801;   Drug: CST-2: Placebo
  Sponsors:   University of Liverpool;   University of Southampton;   Liverpool School of Tropical Medicine;   Lancaster University;   Liverpool University Hospitals NHS Foundation Trust
  Recruiting

• A Study to Evaluate the Efficacy and Safety of Prothione™ Capsules for Mild to Moderate Coronavirus Disease 2019 (COVID-19) - Condition:   Coronavirus Disease 2019 (COVID-19)
  Interventions:   Drug: Placebo;   Drug: Prothione™ (6g)
  Sponsor:   Prothione, LLC
  Not yet recruiting

• Pulmonary Rehabilitation of Patients With a History of COVID-19 - Condition:   Covid19
  Intervention:   Procedure: Pulmonary rehabilitation
  Sponsor:   University of Rzeszow
  Enrolling by invitation

• Ivermectin Role in Covid-19 Clinical Trial - Condition:   Covid19
  Interventions:   Drug: ivermectin;   Drug: hydroxychloroquine;   Drug: Placebo
  Sponsors:   Elaraby Hospital;   Shebin-Elkom Teaching Hospital
  Completed

• Safety, Tolerability and Efficacy Of S-1226 in Moderate Severity Covid-19 Bronchiolitis/Pneumonia - Conditions:   Covid19;   SARS-CoV-2 Infection
  Intervention:   Drug: S-1226
  Sponsor:   SolAeroMed Inc.
  Not yet recruiting

• Community Network-driven COVID-19 Testing of Vulnerable Populations in the Central US - Condition:   Covid19
  Intervention:   Other: Social Network Strategy + COVID-19 messaging
  Sponsor:   University of Chicago
  Not yet recruiting

From PubMed

• Evidence that Ginkgo Biloba could use in the influenza and coronavirus COVID-19 infections - Coronavirus COVID-19 pandemic invades the world. Public health evaluates the incidence of infections and death, which should be reduced and need desperately quarantines for infected individuals. This article review refers to the roles of Ginkgo Biloba to reduce the risk of infection in the respiratory tract, the details on the epidemiology of corona COVID-19 and influenza, and it highlights how the Ginko Biloba could have been used as a novel treatment.Ginkgo Biloba can reduce the risk of…

• Nonstructural protein 7 and 8 complexes of SARS-CoV-2 - The pandemic outbreak of coronavirus disease 2019 (COVID-19) across the world has led to millions of infection cases and caused a global public health crisis. Current research suggests that SARS-CoV-2 is a highly contagious coronavirus that spreads rapidly through communities. To understand the mechanisms of viral replication, it is imperative to investigate coronavirus viral replicase, a huge protein complex comprising up to 16 viral nonstructural and associated host proteins, which is the most…

• Potent, Novel SARS-CoV-2 PLpro Inhibitors Block Viral Replication in Monkey and Human Cell Cultures - Antiviral agents blocking SARS-CoV-2 viral replication are desperately needed to complement vaccination to end the COVID-19 pandemic. Viral replication and assembly are entirely dependent on two viral cysteine proteases: 3C-like protease (3CLpro) and the papain-like protease (PLpro). PLpro also has deubiquitinase (DUB) activity, removing ubiquitin (Ub) and Ub-like modifications from host proteins, disrupting the host immune response. 3CLpro is inhibited by many known cysteine protease…

• Quantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for Cross-Cohort Comparisons of COVID-19 Sera - The global coronavirus disease 2019 (COVID-19) pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent-phase plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous biosafety level 3 (BSL3) conditions, which…

• The Role of Sialylation in Respiratory Viral Infection and Treatment - Respiratory infections caused by viruses such as influenza and coronavirus are a serious global problem due to their high infection rates and potential to spark pandemics, such as the current COVID-19 pandemic. Although preventing these infections by using vaccines has been the most successful strategy to date, effective vaccines are not always available. Therefore, developing broad-spectrum anti-viral drugs to treat such infections is essential, especially in the case of immunocompromised…

• Coronavirus helicases: attractive and unique targets of antiviral drug-development and therapeutic patents - INTRODUCTION: Coronaviruses encode a helicase that is essential for viral replication and represents an excellent antiviral target. However, only a few coronavirus helicase inhibitors have been patented. These patents include drug-like compound SSYA10-001, aryl diketo acids (ADK), and dihydroxychromones. Additionally, adamantane-derived bananins, natural flavonoids, one acrylamide derivative [(E)-3-(furan-2-yl)-N-(4-sulfamoylphenyl)acrylamide], a purine derivative…

• SARS-CoV-2 infection remodels the host protein thermal stability landscape - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health and has compromised economic stability. In addition to the development of an effective vaccine, it is imperative to understand how SARS-CoV-2 hijacks host cellular machineries on a system-wide scale so that potential host-directed therapies can be developed. In situ proteome-wide abundance and thermal stability measurements using thermal proteome profiling (TPP) can inform on global changes in…

• Medicinal plants: Treasure for antiviral drug discovery - The pandemic of viral diseases like novel coronavirus (2019-nCoV) prompted the scientific world to examine antiviral bioactive compounds rather than nucleic acid analogous, protease inhibitors, or other toxic synthetic molecules. The emerging viral infections significantly associated with 2019-nCoV have challenged humanity’s survival. Further, there is a constant emergence of new resistant viral strains that demand novel antiviral agents with fewer side effects and cell toxicity. Despite…

• In vitro selection of an RNA aptamer yields an interleukin-6/interleukin-6 receptor interaction inhibitor - Interleukin-6 (IL-6) binds to the IL-6 receptor (IL-6R) subunit, related to autoimmune diseases and cytokine storm in COVID-19. In this study, we performed systematic evolution of ligands by exponential enrichment and identified a novel RNA aptamer. This RNA aptamer not only bound to IL-6R with a dissociation constant of 200 n m, but also inhibited the interaction of IL-6R with IL-6.

• De novo design of new chemical entities for SARS-CoV-2 using artificial intelligence - Background: The novel coronavirus SARS-CoV-2 has severely affected the health and economy of several countries. Multiple studies are in progress to design novel therapeutics against the potential target proteins in SARS-CoV-2, including 3CL protease, an essential protein for virus replication. Materials & methods: In this study we employed deep neural network-based generative and predictive models for de novo design of small molecules capable of inhibiting the 3CL protease. The generative model…

• Are vanadium complexes druggable against the main protease m(pro) of sars-cov-2? - a computational approach - In silico techniques helped explore the binding capacities of the SARS-CoV-2 main protease (M^(pro)) for a series of metalloorganic compounds. Along with small size vanadium complexes a vanadium-containing derivative of the peptide-like inhibitor N3 (N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-l-valyl-N1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl] methyl }but-2-enyl)-l-leucinamide) was designed from the crystal structure with PDB entry code 6LU7. On theoretical grounds our…

• Effect of Chloroquine and Hydroxychloroquine on COVID-19 Virological Outcomes: An Updated Meta-Analysis - As anti-malarial drugs have been found to inhibit Corona viruses in vitro, studies have evaluated the effect of these drugs inCOVID-19 infection. We conducted an updated meta-analysis of clinical trials and observational studies published till June 2020. Patients with reverse transcription polymerase chain reaction (RT-PCR) confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (COVID-19) infection were included. The drugs used in the intervention group are Chloroquine (CQ)/Hydroxychloroquine…

• EGCG, a green tea polyphenol, inhibits human coronavirus replication in vitro - COVID-19 pandemic results in record high deaths in many countries. Although a vaccine for SARS-CoV-2 is now available, effective antiviral drugs to treat coronavirus diseases are not available yet. Recently, EGCG, a green tea polyphenol, was reported to inhibit SARS-CoV-2 3CL-protease, however the effect of EGCG on coronavirus replication is unknown. In this report, human coronavirus HCoV-OC43 (beta coronavirus) and HCoV-229E (alpha coronavirus) were used to examine the effect of EGCG on…

• Discovery and structural optimization of 3-O-beta-chacotriosyl oleanane-type triterpenoids as potent entry inhibitors of SARS-CoV-2 virus infections - Currently, SARS-CoV-2 virus is an emerging pathogen that has posed a serious threat to public health worldwide. However, no agents have been approved to treat SARS-CoV-2 infections to date, underscoring the great need for effective and practical therapies for SARS-CoV-2 outbreaks. We reported that a focused screen of OA saponins identified 3-O-β-chacotriosyl OA benzyl ester 2 as a novel small molecule inhibitor of SARS-CoV-2 virus entry, via binding to SARS-CoV-2 glycoprotein (S). We performed…

• Neutralizing antibodies targeting the SARS-CoV-2 receptor binding domain isolated from a naive human antibody library - Infection with SARS-CoV-2 elicits robust antibody responses in some patients, with a majority of the response directed at the receptor binding domain (RBD) of the spike surface glycoprotein. Remarkably, many patient-derived antibodies that potently inhibit viral infection harbor few to no mutations from the germline, suggesting that naïve antibody libraries are a viable means for discovery of novel SARS-CoV-2 neutralizing antibodies. Here, we used a yeast surface-display library of human naïve…

From Patent Search

• Compositions and methods for detecting SARS-CoV-2 spike protein - - link

• 新冠病毒疫苗表达抗原蛋白的电化学发光免疫检测试剂盒 - 本发明提供一种新冠病毒疫苗表达抗原蛋白的电化学发光免疫检测试剂盒，所述试剂盒至少包含：包被有链霉亲和素的孔板、生物素标记的抗新冠棘突蛋白抗体1、SULFO标记的抗新冠棘突蛋白抗体2、洗涤液、读数液、新冠病毒S蛋白标准品和新冠病毒RBD蛋白标准品。本发明以生物素标记的抗新冠棘突蛋白的抗体1与链霉亲和素板进行连接作为固定相，以新冠S蛋白、RBD蛋白作为参照品，可被SULFO标记的抗体2识别，从而检测新冠抗原的表达情况。该试剂盒能准确灵敏地定量检测不同基质中的新冠S蛋白、RBD蛋白，样品的前处理过程简单，耗时少，可同时检测大量样品。本发明对于大批量样品的新冠病毒疫苗表达抗原的检测具有重要意义。 - link

• 陶瓷复合涂料、杀毒陶瓷复合涂料及其制备方法和涂层 - 本发明是关于一种陶瓷复合涂料、杀毒陶瓷复合涂料及其制备方法和涂层。该涂料包括30_{99.9%无机树脂、0.1}70%氮化硅、0_{10%功能助剂、0}18%无机颜料和0_{2%其他功能助剂；无机树脂由有机烷氧基硅烷、有机溶剂和硅溶胶混合、反应，抽醇，添加去离子水获得；有机烷氧基硅烷、有机溶剂和硅溶胶的质量比为1}1.6：0.5~0.8：1。所要解决的技术问题是如何制备一种贮存稳定性好、可常温固化且膜层的物理化学性能优异的涂料；该涂料VOC含量低，具有良好的安全生产性，且涂料成膜过程中的VOC排放很低，利于环保；该膜层的硬度高、柔韧性好，不易开裂，且可以接触性杀灭病毒和细菌；该涂料既可常温固化，也可加热固化，无需现场两个剂型调配，施工方便，成本节约，从而更加适于实用。 - link

• SARS-CoV-2 antibodies - - link

• SARS-CoV-2 antibodies - - link

• 病毒核酸提取或保存试剂、引物探针组合、病毒扩增试剂、试剂盒及其应用 - 本发明涉及病毒检测领域，特别涉及病毒核酸提取或保存试剂、引物探针组合、病毒扩增试剂、试剂盒及其应用。本发明病毒检测装置提供了一种简单易行的病毒核酸提取方法，整个过程大约5‑15分钟，回收纯化的核酸，可用于病毒核酸的检测。包括PCR、NASBA、LAMP、RPA等。相比较于传统的病毒提取方法，本方法病毒核酸回收率高、用时少、操作方便、易于临床推广。本发明涉及单管同时检测新型冠状病毒COVID‑19 N和ORF基因以及人源内参基因的等温扩增引物、探针组合序列和反应缓冲液，该体系特异性好，灵敏度高（50 cp/mL），特异性高，只需20 min的检测时间，最快可在10 min左右报阳性。 - link

• 一种侧链修饰的聚氨基酸及其制备方法和用途 - 本发明提供了一种侧链修饰的聚氨基酸及其制备方法，所述侧链修饰的聚氨基酸具有如下优势：（1）主链和侧链结构及其连接方式都可以灵活选取，使制得的聚合物胶束具有良好生物相容性和靶向递送效率，（2）聚氨基酸主链的电荷极性为电正性，对主链的电荷调节促进胶束的pH值响应，帮助RNA从“溶酶体陷阱”中逃离进入胞浆，（3）通过量化侧链修饰脂肪链的链长、饱和度和脂肪链数量来控制侧链的疏水性部分，精确调节疏水部分的体积和缔合作用强度，（4）由于RNA和DNA在结构和负电性上的相似性，高效构建包裹和递送体，（5）通过双亲性功能高分子的侧链修饰引入不同的生物功能基团，实现递送体系对靶点组织和部位的特异性结合，提高靶向递送效果。 - link

• 靶向SARS-CoV-2冠状病毒的抗体及其诊断和检测用途 - 本发明涉及靶向SARS‑CoV‑2冠状病毒的抗体及其诊断和检测用途。具体涉及特异性结合冠状病毒S蛋白的抗体或其抗原结合片段和抗体对以及包含所述抗体或其抗原结合片段和抗体对的检测产品。本发明还涉及编码所述抗体或抗原结合片段的核酸及包含其的宿主细胞，以及制备所述抗体或抗原结合片段的方法。此外，本发明涉及所述抗体或其抗原结合片段、抗体对的预防、治疗或诊断用途。相较于常规的IgG/IgM检测，该检测方法直接检测样本中病毒的RBD蛋白，可以有效避免可能的样本中无关IgG/IgM对于检测的干扰，有效提高检测的灵敏度。所述抗体或抗体对可用于诊断和/或检测冠状病毒。 - link

• A PHARMACEUTICAL COMPOSITION OF NITAZOXANIDE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of a nitazoxanide or its pharmaceutically acceptable salts thereof and an mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the nitazoxanide in the ratio of 0.05% to 66% w/v and the mefloquine in the ratio of 0.05% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of nitazoxanide and mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. - link

• TREATMENT OF COVID-19 WITH REBAMIPIDE - - link