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Unraveling the binding mechanism of the active form of Remdesivir to RdRp of SARS-CoV-2 and designing new potential analogues: Insights from molecular dynamics simulations.

ABSTRACT: The binding of the active form of Remdesivir (RTP) to RNA-dependent RNA Polymerase (RdRp) of SARS-CoV-2 was studied using molecular dynamics simulation. The RTP maintained the interactions observed in the experimental cryo-EM structure. Next, we designed new analogues of RTP, which not only binds to the RNA primer strand in a similar pose as that of RTP, but also binds more strongly than RTP does as predicted by MM-PBSA binding energy. This suggest that these analogues might be able to covalently link to the primer strand as RTP, but their 3' modification would terminate the primer strand growth.

SUBMITTER: Arba M

PROVIDER: S-EPMC9020840 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Unraveling the binding mechanism of the active form of Remdesivir to RdRp of SARS-CoV-2 and designing new potential analogues: Insights from molecular dynamics simulations.

Arba Muhammad M Paradis Nicholas N Wahyudi Setyanto T ST Brunt Dylan J DJ Hausman Katherine R KR Lakernick Phillip M PM Singh Mursalin M Wu Chun C

Chemical physics letters 20220420

The binding of the active form of Remdesivir (RTP) to RNA-dependent RNA Polymerase (RdRp) of SARS-CoV-2 was studied using molecular dynamics simulation. The RTP maintained the interactions observed in the experimental cryo-EM structure. Next, we designed new analogues of RTP, which not only binds to the RNA primer strand in a similar pose as that of RTP, but also binds more strongly than RTP does as predicted by MM-PBSA binding energy. This suggest that these analogues might be able to covalentl ...[more]

PMID: 35475235

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