Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the harm caused by coronaviruses to the world cannot be underestimated. Recently, a novel coronavirus (severe acute respiratory syndrome coronavirus‐2 [SARS‐CoV‐2]) initially found to trigger human severe respiratory illness in Wuhan City of China in 2019, has infected more than six million people worldwide by 21 June 2020, and which has been recognized as a public health emergency of international concern as well. And the virus has spread to more than 200 countries around the world. However, the effective drug has not yet been officially licensed or approved to treat SARS‐Cov‐2 and SARS‐Cov infection. NSP12‐NSP7‐NSP8 complex of SARS‐CoV‐2 or SARS‐CoV, essential for viral replication and transcription, is generally regarded as a potential target to fight against the virus. According to the NSP12‐NSP7‐NSP8 complex (PDB ID: 7BW4) structure of SARS‐CoV‐2 and the NSP12‐NSP7‐NSP8 complex (PDB ID: 6NUR) structure of SARS‐CoV, NSP12‐NSP7 interface model, and NSP12‐NSP8 interface model were established for virtual screening in the present study. Eight compounds (Nilotinib, Saquinavir, Tipranavir, Lonafarnib, Tegobuvir, Olysio, Filibuvir, and Cepharanthine) were selected for binding free energy calculations based on virtual screening and docking scores. All eight compounds can combine well with NSP12‐NSP7‐NSP8 in the crystal structure, providing drug candidates for the treatment and prevention of coronavirus disease 2019 and SARS.
A novel coronavirus (SARS-CoV-2) that is initially found to trigger human severe respiratory illness in Wuhan City of China in 2019, has killed 2,718 people in China by February 26, 2020, and which has been recognized as a public health emergency of international concern as well. And the virus has spread to more than 38 countries around the world. However, the drug has not yet been officially licensed or approved to treat SARS-Cov-2 infection. NSP12-NSP7-NSP8 complex of SARS-CoV-2, essential for viral replication and transcription, is generally regarded as a potential target to fight against the virus. According to the NSP12-NSP7-NSP8 complex (PDB ID: 6NUR) structure of SARS, two homologous models were established for virtual screening in the present study, namely NSP12-NSP7 interface model and NSP12-NSP8 interface model. Seven compounds (Saquinavir, Tipranavir, Lonafarnib, Tegobuvir, Olysio, Filibuvir, and Cepharanthine) were selected for binding free energy calculations based on virtual screening and docking scores. All seven compounds can combine well with NSP12-NSP7-NSP8 in the homologous model, providing drug candidates for the treatment and prevention of SARS-CoV-2.
Recently, a few animals have been frequently reported to have been diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether they are SARS-CoV-2 intermediate hosts is worthy of great attention. The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from 10 kinds of animals. Results show that chimpanzees, domestic cats and cattles are more susceptible to infection by SARS-CoV-2. Cats in particular, such as pet cats and stray cats, interact very closely with humans, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic. Furthermore, based on ACE2(cats)-SARS-CoV-2-RBD model, through high-throughput screening methods using a pool of 30,000 small molecules, eight compounds were selected for binding free energy calculations. All the eight compounds can effectively interfere with the binding of ACE2 and Spike protein, especially Nelfinavir, providing drug candidates for the treatment and prevention of SARS-CoV-2, suggesting further assessment of the anti-SARS-CoV-2 activity of these compounds in cell culture. Although we only reported the results of the simulation, and more laboratory and epidemiological investigation are required. Like cats are a risk factor, we can further detect SARS-CoV-2 according to the susceptibility of different animals, find the potential host of infection, and completely cut off the living space of the virus. Especially, cats could be a choice of animal model for screening antiviral drugs or vaccine candidates against SARS-CoV-2.
Back Cover Caption: The cover image is based on the Research Article SARS‐CoV‐2 and SARS‐CoV: Virtual Screening of Potential inhibitors targeting RNA‐dependent RNA polymerase activity (NSP12) by Zijing Ruan et al., https://doi.org/10.1002/jmv.26222.
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