Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein.
TLDR
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 RBDand ACE2 when judging any potential candidate.Abstract:
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.read more
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Modelling conformational state dynamics and its role on infection for SARS-CoV-2 Spike protein variants
TL;DR: The SARS-CoV-2 Spike protein needs to be in an open-state conformation to interact with ACE2 as part of the viral entry mechanism, and coarse-grained normal-mode analyses are used to model the dynamics of Spike and calculate transition probabilities between states for 17081 Spike variants.
Journal ArticleDOI
Modelling conformational state dynamics and its role on infection for SARS-CoV-2 Spike protein variants.
TL;DR: In this article, the authors used coarse-grained normal mode analysis to model the dynamics of Spike and calculate transition probabilities between states for 17081 variants including experimentally observed variants.
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Accelerating COVID-19 Research Using Molecular Dynamics Simulation.
TL;DR: How MD simulation has been explored by the scientific community to accelerate and guide translational research on SARS-CoV-2 in the past year is discussed and future research directions for researchers are considered, where MD simulations can help fill the existing gaps in COVID-19 research.
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The tyrosine kinase inhibitor nilotinib inhibits SARS-CoV-2 In Vitro.
Valeria Cagno,Gaëlle Magliocco,Gaëlle Magliocco,Caroline Tapparel,Youssef Daali,Youssef Daali +5 more
TL;DR: In vitro activity of nilotinib, imatinib and dasatinib, three Abl tyrosine kinase inhibitors, against SARS‐CoV‐2 shows antiviral efficacy, making this compound a potential candidate for treatment of COVID‐19 in vivo.
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