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 5月 2020
Accepted
30 6月 2020
First published
30 6月 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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements