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SARS-CoV-2 / Covid-19                            NEWS  PAGE      

 Crown copyright – image supplied by Matthew Hannah, Public Health England             

 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
 
A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19
A randomized, controlled, open-label trial of lopinavir–ritonavir in hospitalized adult patients with severe Covid-19 did not show any benefit beyond standard care … read more
 

 PRECLINICAL 

Remdesivir and Chloroquine Effectively Inhibit the Recently Emerged Novel Coronavirus (2019-nCoV) in Vitro
This study, which evaluated the antiviral activity of seven drugs against a clinical isolate of 2019-nCoV in vitro, revealed that remdesivir and chloroquine are highly effective in the control of 2019-nCoV infection in vitro, suggesting that they should be assessed in human patients … read more

 

Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV                                                                                     
Remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improved pulmonary function and reduced lung viral loads and severe lung pathology … read more

 

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

 

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-Based Stabilization of Non-native ProteinProtein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design
Virtual screening identified 5-benzyloxygramine as an inhibitor of MERS-CoV in vitro by inducing abnormal N protein oligomerization … read more

 

Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2
This study uses an integrative, antiviral drug repurposing methodology, implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV–host interactome and drug targets in the human protein–protein interaction network, to prioritize 16 potential anti-HCoV repurposable drugs and identify three potential drug combinations … read more   .

 

The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells                                                  
The report also shows that the TMPRSS2 inhibitor camostat mesylate blocked entry and might constitute a treatment option … read more 
 
 
Potent Binding of 2019 Novel Coronavirus Spike Protein by a SARS Coronavirus-Specific Human Monoclonal Antibody                                                                                                     
A SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections read more

 VIROLOGY 
The Spike Glycoprotein of the New Coronavirus 2019-nCoV Contains a Furin-Like Cleavage Site Absent in CoV of the Same Clade                                                                
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   
 

  REVIEWS  

Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases
This special report highlights antiviral strategies involving small molecules and biologics targeting complex molecular interactions involved in coronavirus infection and replication, and drug-repurposing of agents known to be effective against other RNA viruses including SARS-CoV and MERS-CoV … read more

 

Therapeutic options for the 2019 novel coronavirus (2019-nCoV)
This review discusses the potential for repurposing existing antiviral agents to treat COVID-19, some of which are entering clinical trials … read more

 

Discovering drugs to treat coronavirus disease 2019 (COVID-19)
This article summarizes pre-clinical and preliminary clinical studies of agents with potential efficacy against SARS-CoV-2 … read more  
 
Of chloroquine and COVID-19
This review considers the possible benefit of chloroquine in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2) in light of previous experiments with chloroquine in the field of antiviral research … 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
Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses
This article presents a rationale for considering these drugs for investigation as potential treatment options for COVID-19 … read more

 

Some Drugs for COVID-19
Considers whether currently available drugs could be effective in treating COVID-19...read more

 

Perspectives on Monoclonal Antibody Therapy as Potential Therapeutic Intervention for Coronavirus disease-19 (COVID-19)
This review summarize the potential monoclonal antibody based therapeutic intervention for COVID-19 by considering the existing knowledge on the neutralizing monoclonal antibodies against similar coronaviruses SARS-CoV and MERS-CoV. Further research on COVID-19 pathogenesis could identify appropriate therapeutic targets to develop specific anti-virals against this newly emerging pathogen … read more
 

 

 

Selection of articles and research prepared by: Dr. Edin Mifsud and Ms Rubaiyea Farrukee (WHO Collaborating Centre for Influenza, Melbourne)