Mechanism of inhibition of SARS-CoV-2 Mpro by N3 peptidyl Michael acceptor explained by QM/MM simulations and design of new derivatives with tunable chemical reactivity-Reference-Cited by-同舟云学术

Mechanism of inhibition of SARS-CoV-2 Mpro by N3 peptidyl Michael acceptor explained by QM/MM simulations and design of new derivatives with tunable chemical reactivity

Published:2021 Issue:4 Volume:12 Page:1433-1444
ISSN:2041-6520
Container-title:Chemical Science
language:en
Short-container-title:Chem. Sci.

Author:

Arafet Kemel¹²³⁴^ORCID,Serrano-Aparicio Natalia¹²³⁴^ORCID,Lodola Alessio⁵⁶⁷^ORCID,Mulholland Adrian J.⁸⁹¹⁰¹¹^ORCID,González Florenci V.¹²²³⁴^ORCID,Świderek Katarzyna¹²³⁴^ORCID,Moliner Vicent¹²³⁴^ORCID

Affiliation:

1. Departament de Química Física i Analítica

2. Universitat Jaume I

3. 12071 Castelló

4. Spain

5. Dipartimento di Scienze degli Alimenti e del Farmaco

6. Università degli Studi di Parma

7. Italy

8. Centre for Computational Chemistry

9. School of Chemistry

10. University of Bristol

11. UK

12. Departament de Química Inorgànica i Orgànica

Abstract

QM/MM simulations identify the mechanism of reaction of N3, a covalent peptidyl inhibitor of SARS-CoV-2 main protease. Modelling of two novel proposed compounds, B1 and B2, suggests that reversibility of covalent inhibition could be tailored.

Funder

Generalitat Valenciana

Universitat Jaume I

Engineering and Physical Sciences Research Council

British Society for Antimicrobial Chemotherapy

Ministerio de Ciencia, Innovación y Universidades

Ministerio de Economía y Competitividad

Publisher

Royal Society of Chemistry (RSC)

Subject

General Chemistry

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