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

Muhammad Arba, Nicholas Paradis, Setyanto T. Wahyudi, Dylan J. Brunt, Katherine R. Hausman, Phillip M. Lakernick, Mursalin Singh, Chun Wu

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Article number139638
JournalChemical Physics Letters
Volume799
DOIs
StatePublished - Jul 16 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Physics and Astronomy
  • Physical and Theoretical Chemistry

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this