Issue 62, 2020

Interaction of hydroxychloroquine with SARS-CoV2 functional proteins using all-atoms non-equilibrium alchemical simulations

Abstract

Using a combination of enhanced sampling molecular dynamics techniques and non-equilibrium alchemical transformations with full atomistic details, we have shown that hydroxychloroquine (HCQ) may act as a mild inhibitor of important functional proteins for SARS-CoV2 replication, with potency increasing in the series PLpro, 3CLpro, RdRp. By analyzing the bound state configurations, we were able to improve the potency for the 3CLpro target, designing a novel HCQ-inspired compound, named PMP329, with predicted nanomolar activity. If confirmed in vitro, our results provide a molecular rationale for the use of HCQ or of strictly related derivatives in the treatment of Covid-19.

Graphical abstract: Interaction of hydroxychloroquine with SARS-CoV2 functional proteins using all-atoms non-equilibrium alchemical simulations

Supplementary files

Article information

Article type
Communication
Submitted
18 Mud 2020
Accepted
30 Kho 2020
First published
30 Kho 2020

Chem. Commun., 2020,56, 8854-8856

Interaction of hydroxychloroquine with SARS-CoV2 functional proteins using all-atoms non-equilibrium alchemical simulations

P. Procacci, M. Macchiagodena, M. Pagliai, G. Guarnieri and F. Iannone, Chem. Commun., 2020, 56, 8854 DOI: 10.1039/D0CC03558K

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