isirv Antiviral Group
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SARS-CoV-2 / Covid-19 NEWS PAGE Crown copyright – image supplied by Matthew Hannah, Public Health England |
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CLINICAL A novel coronavirus outbreak of global health concern
This early report compares the clinical features of patients infected with 2019-nCoV with patients infected with SARS-CoV or MERS-CoV and explains the extraordinary public health measures implemented to reduce spread of the virus
Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study
This rapid prospective investigation of patients with covid-19 admitted to hospital in England, Wales, and Scotland showed that obesity, chronic kidney disease, and liver disease were also risk factors, associated with increased hospital mortality … read more
Viral dynamics in mild and severe cases of COVID-19
Data indicate that, similar to SARS in 2002–03, patients with severe COVID-19 tend to have a high viral load and a long virus shedding period, and suggest that the viral load of SARS-CoV-2 might be a useful marker for assessing disease severity and prognosis … read more
Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections
The study shows that asymptomatic patients shed virus for longer and have reduced immune responses compared to symptomatic patients … read more
Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients
An integrated immune analysis on a cohort of 50 COVID-19 patients, with various disease severity, identified in severe and critical patients a highly impaired interferon type I response, associated with a persistent blood viral load and an exacerbated inflammatory response … read more
An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study.
The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease … read more
Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial
In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies … read more
Remdesivir for the Treatment of Covid-19 — Preliminary Report
Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection … read more
PRECLINICAL Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro
The study also showed that remdesivir and emetine were synergistic in inhibiting SARS-CoV-2 replication … read more
Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency Favourable selectivity for remdesivir triphosphate over ATP and delayed chain termination at position i+3 are key elements of a refined mechanism of inhibition observed with SARS-CoV, MERS-CoV, and SARS-CoV-2 polymerase complexes …read more
Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase
The study extends the known breadth and antiviral activity of remdesivir to include both contemporary human and highly divergent zoonotic coronaviruses … read more
Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia
SARS-CoV-2 infection of human airway epithelial cultures was used to provide evidence on the antiviral efficacy of remdesivir and the therapeutic potential of the remdesivir-diltiazem combination …read more
Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
Early remdesivir treatment had a clear clinical benefit in SARS-CoV-2-infected rhesus macaques, supporting early remdesivir treatment in COVID-19 patients to prevent progression to severe pneumonia … read more
Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase
This study shows that Favipiravir inhibits the SARS-CoV-2 RdRp complex as a nucleotide analogue through a combination of chain termination, slowed RNA synthesis and lethal mutagenesis, supporting nucleoside analogues as promising candidates for the treatment of COVID-19 … read more
A library of nucleotide analogues terminate RNA synthesis catalyzed by polymerases of coronaviruses that cause SARS and COVID-19
A library of nucleoside triphosphate analogues, with a variety of structural and chemical features, were evaluated as inhibitors of the RdRps of SARS-CoV and SARS-CoV-2, with the goal of identifying nucleotide analogues that not only terminate RNA synthesis but also have the potential to resist the viruses' exonuclease activity … read more
The FDA-approved Drug Ivermectin inhibits the replication of SARS- CoV-2 in vitro
Ivermectin, an FDA-approved anti-parasitic agent with broad spectrum anti-viral activity in vitro, inhibited the replication of SARS-CoV-2 … read more
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice
The ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) was shown to have broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. An orally bioavailable prodrug improved pulmonary function, and reduced virus titer and body weight loss in mice infected with SARS-CoV or MERS-CoV … read more
Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors
This article reports the X-ray structures of SARS-CoV-2 Mpro and its complex with a potent α-ketoamide inhibitor with pronounced lung tropism and suitability for administration by inhalation … read more
Structure of Mpro from COVID-19 virus and discovery of its inhibitors
In this study, the combination of structure-based drug design, virtual screening and high-throughput screening proved to be an efficient strategy to identify antiviral leads that target the COVID-19 virus main protease (Mpro) …read more
Molecular Investigation of SARS–CoV-2 Proteins and Their Interactions with Antiviral Drugs
In this study the molecular docking approach was used to analyze the affinity between different viral proteins and several inhibitors, originally developed for other viral infections, to assist development of new antiviral agents against COVID-19 …read more
The Zinc Finger Antiviral Protein restricts SARS-CoV-2
This study shows that Zinc finger antiviral protein (ZAP) that specifically targets CpG dinucleotides in viral RNA sequences restricts SARS-CoV-2 … read more
Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV
The study highlights the functionality of individual proteins as well as vulnerability hotspots of SARS-CoV-2, to target with clinically approved drugs, and identifies kinase inhibitors as well as MMPase inhibitors with significant antiviral effects against SARS-CoV-2 … read more
Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion
EK1C4, of a series of lipopeptides, was found to be the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection and was highly effective against other human coronaviruses. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection … read more
Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity
An HR2 sequence-based lipopeptide fusion inhibitor, IPB02, showed highly potent activities in inhibiting SARS-CoV-2 S protein-mediated cell-cell fusion and pseudovirus transduction. The structure-activity relationship (SAR) of IPB02 provides important information for understanding the entry pathway of SARS-CoV-2 and the design of antivirals that target the membrane fusion step … read more
Nafamostat Mesylate Blocks Activation of SARS-CoV-2: New Treatment Option for COVID-19
The authors report that nafamostat mesylate blocked SARS-CoV-2 infection of human lung cells with markedly higher efficiency than camostat mesylate,with a EC50 in the low-nanomolar range, and argue that it should be evaluated in clinical trials as a COVID-19 treatment...read more
The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner.
The findings, together with accumulated clinical data regarding nafamostat’s safety, make it a likely candidate drug to treat COVID-19 … read more
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
Using cryo-EM and binding assays, S309 was shown to recognize an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants … read more
Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability
Monoclonal antibodies, isolated from three convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein, were shown to target multiple distinct antigenic sites. Some with potent picomolar neutralizing activities are promising candidates for COVID-19 treatment … read more
A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV.
A crystal structure of CR3022, a neutralizing antibody, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein shows that CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV … read more
VIROLOGY
Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor
The crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2 revealed that the overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, indicating convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2 … read more
Structural basis of receptor recognition by SARS-CoV-2.
The crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 in complex with ACE2 in comparison with the SARS-CoV RBD reveals structural features of SARS-CoV-2 RBD which increase its ACE2-binding affinity, and shed light on the potential animal-to-human transmission of SARS-CoV-2 …read more
Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2
Cryo-EM structures of human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, show that the ACE2-B0AT1 complex is assembled as a dimer of heterodimers, and that the RBD is recognized by the extracellular peptidase domain of ACE2, providing important insights into the molecular basis for coronavirus recognition and infection … read more
The article discusses the functional significance of the cleavage site and its possible consequences for pathogenicity, and its potential implication for antiviral development … read more
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Biophysical and structural data provide evidence that the 2019-nCoV S protein binds ACE2 with higher affinity than does SARS-CoV S. Several SARS-CoV RBD-specific monoclonal antibodies do not have appreciable binding to 2019-nCoV S, suggesting limited antibody cross-reactivity between the two RBDs … read more
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
The high affinity of SARS-CoV-2 S for human ACE2, similar to that of SARS-CoV S, and the possession of a furin-like cleavage site correlate with efficient human transmissibility and pathogenicity. Determination of cryo-EM structures of the trimeric ectodomain provides a basis for design of vaccines and inhibitors of viral entry … read more
Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus
A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic and may have a fitness advantage … read more
Structures of Human Antibodies Bound to SARSCoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies
This Investigation of the diversity of antibodies in plasma of convalescent COVID-19 patients and the S epitopes targeted provides criteria for evaluating vaccine-elicited antibodies … read more
Structure of the RNA-dependent RNA polymerase from COVID-19 virus
A cryo-EM structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-Å resolution shows how remdesivir binds to this polymerase and provides a basis for the design of new antiviral therapeutics … read more
Structure of replicating SARS-CoV-2 polymerase
The cryo-EM structure of the SARS-CoV-2 RdRp in its replicating form, comprising the viral proteins nsp12, nsp8, and nsp7 and over two turns of RNA template-product duplex, will allow for a detailed analysis of the inhibitory mechanisms used by antivirals such as remdesivir … read more
Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir
Cryo-EM structures of the SARS-CoV-2 RdRp, either in the apo form or in complex with a 50-base template-primer RNA and remdesivir, reveal critical insights into the mechanism of viral RNA replication and inhibition by remdesivir … read more
Structural Basis of the Potential Binding Mechanism of Remdesivir to SARS-CoV‑2 RNA-Dependent RNA Polymerase
Molecular dynamics simulations and free energy perturbation methods were used to study the mechanism of remdesivir inhibition of the RNA-dependent RNA polymerase of SARS-CoV-2 virus … read more
Infection and Rapid Transmission of SARS-CoV-2 in Ferrets
A ferret model of SARS-CoV-2 infection and transmission recapitulates aspects of human disease and represents a model of COVID-19 that may facilitate development of SARS-CoV-2 therapeutics and vaccines … read more
Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection
A platform for ultra-high-throughput serum and plasma proteomics, that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories, identified 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19 … read more
REVIEWS Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus
This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections …read more
A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir
This comprehensive review presents information on remdesivir, a broad-spectrum viral RNA-dependent RNA polymerase inhibitor, including preclinical research and clinical trials, and provides a perspective regarding its use for the treatment of COVID-19 … read more
Molecular structure analyses suggest strategies to therapeutically target SARS-CoV-2
This commentary highlights some of the latest studies that provide atomic-resolution structural details imperative for the development of vaccines and antiviral therapeutics … read more
A Systematic Review on the Efficacy and Safety of Chloroquine for the Treatment of COVID-19
Considers the pre-clinical rationale and evidence regarding the effectiveness of chloroquine for treatment of COVID-19 as well as evidence of safety from long-time use in clinical practice for other indications to justify clinical research on the topic … read more
Some Drugs for COVID-19
Considers whether currently available drugs could be effective in treating COVID-19...read more
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Selection of articles and research prepared by: Dr. Edin Mifsud and Ms Rubaiyea Farrukee
WHO Collaborating Centre for Influenza, Melbourne
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