Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein

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    The recent outbreak of the respiratory syndrome-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease (COVID-19). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs approved for other diseases. The first interaction between the virus and the host cell is mediated by the spike protein on the virus surface and the human angiotensin-converting enzyme (ACE2). Small molecules able to bind the receptor-binding domain (RBD) of the spike protein and disrupt the binding to ACE2 would offer an important tool for slowing, or even preventing, the infection. Here, we screened 2421 approved small molecules in silico and validated the docking outcomes through extensive molecular dynamics simulations. Out of six drugs characterized as putative RBD binders, the cephalosporin antibiotic cefsulodin was further assessed for its effect on the binding between the RBD and ACE2, suggesting that it is important to consider the dynamic formation of the heterodimer between RBD and ACE2 when judging any potential candidate.

    Original languageEnglish
    Pages (from-to)195-207
    Number of pages13
    JournalJournal of Computer-Aided Molecular Design
    Issue number2
    Early online date26 Oct 2020
    Publication statusPublished - Feb 2021

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    Leverhulme Trust Grant No. RPG-2017-255.


    • COVID-19
    • Drug repurposing
    • Molecular dynamics
    • SARS-CoV-2
    • Spike protein
    • Supervised molecular dynamics

    ASJC Scopus subject areas

    • Drug Discovery
    • Computer Science Applications
    • Physical and Theoretical Chemistry


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