TY - JOUR
T1 - Unraveling the binding mechanism of the active form of Remdesivir to RdRp of SARS-CoV-2 and designing new potential analogues
T2 - Insights from molecular dynamics simulations
AU - Arba, Muhammad
AU - Paradis, Nicholas
AU - Wahyudi, Setyanto T.
AU - Brunt, Dylan J.
AU - Hausman, Katherine R.
AU - Lakernick, Phillip M.
AU - Singh, Mursalin
AU - Wu, Chun
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/7/16
Y1 - 2022/7/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cplett.2022.139638
DO - 10.1016/j.cplett.2022.139638
M3 - Article
AN - SCOPUS:85129296132
SN - 0009-2614
VL - 799
JO - Chemical Physics Letters
JF - Chemical Physics Letters
M1 - 139638
ER -