Issue 72, 2021
From the journal:

Chemical Communications

Computational simulations on the binding and reactivity of a nitrile inhibitor of the SARS-CoV-2 main protease†

Carlos A. Ramos-Guzmán, ORCID logo a   J. Javier Ruiz-Pernía ORCID logo *a  and  Iñaki Tuñón ORCID logo *a  

* Corresponding authors

a Departamento de Química Física, Universidad de Valencia, 46100 Burjassot, Spain
E-mail: j.javier.ruiz@uv.es, ignacio.tunon@uv.es

Abstract

We present a detailed computational analysis of the binding mode and reactivity of the novel oral inhibitor PF-07321332 developed against the SARS-CoV-2 3CL protease. Alchemical free energy calculations suggest that positions P3 and P4 could be susceptible to improvement in order to get a larger binding strength. QM/MM simulations unveil the reaction mechanism for covalent inhibition, showing that the nitrile warhead facilitates the recruitment of a water molecule for the proton transfer step.

Graphical abstract: Computational simulations on the binding and reactivity of a nitrile inhibitor of the SARS-CoV-2 main protease

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Article information

DOI
https://doi.org/10.1039/D1CC03953A
Article type
Communication
Submitted
21 Jul 2021
Accepted
10 Aug 2021
First published
10 Aug 2021

Chem. Commun., 2021,57, 9096-9099

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Computational simulations on the binding and reactivity of a nitrile inhibitor of the SARS-CoV-2 main protease

C. A. Ramos-Guzmán, J. J. Ruiz-Pernía and I. Tuñón, Chem. Commun., 2021, 57, 9096 DOI: 10.1039/D1CC03953A

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