Covalent narlaprevir- and boceprevir-derived hybrid inhibitors of SARS-CoV-2 main protease

Daniel W. Kneller; Hui Li; Gwyndalyn Phillips; Kevin L. Weiss; Qiu Zhang; Mark A. Arnould; Colleen B. Jonsson; Surekha Surendranathan; Jyothi Parvathareddy; Matthew P. Blakeley; Leighton Coates; John M. Louis; Peter V. Bonnesen; Andrey Kovalevsky

doi:10.1038/s41467-022-29915-z

Nature Communications (Apr 2022)

Covalent narlaprevir- and boceprevir-derived hybrid inhibitors of SARS-CoV-2 main protease

Daniel W. Kneller,
Hui Li,
Gwyndalyn Phillips,
Kevin L. Weiss,
Qiu Zhang,
Mark A. Arnould,
Colleen B. Jonsson,
Surekha Surendranathan,
Jyothi Parvathareddy,
Matthew P. Blakeley,
Leighton Coates,
John M. Louis,
Peter V. Bonnesen,
Andrey Kovalevsky

Affiliations

Daniel W. Kneller: Neutron Scattering Division, Oak Ridge National Laboratory
Hui Li: Center for Nanophase Materials Sciences, Oak Ridge National Laboratory
Gwyndalyn Phillips: Neutron Scattering Division, Oak Ridge National Laboratory
Kevin L. Weiss: Neutron Scattering Division, Oak Ridge National Laboratory
Qiu Zhang: Neutron Scattering Division, Oak Ridge National Laboratory
Mark A. Arnould: Center for Nanophase Materials Sciences, Oak Ridge National Laboratory
Colleen B. Jonsson: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center
Surekha Surendranathan: Regional Biocontainment Laboratory, The University of Tennessee Health Science Center
Jyothi Parvathareddy: Regional Biocontainment Laboratory, The University of Tennessee Health Science Center
Matthew P. Blakeley: Large Scale Structures Group, Institut Laue–Langevin
Leighton Coates: Second Target Station, Oak Ridge National Laboratory
John M. Louis: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS
Peter V. Bonnesen: Center for Nanophase Materials Sciences, Oak Ridge National Laboratory
Andrey Kovalevsky: Neutron Scattering Division, Oak Ridge National Laboratory

DOI: https://doi.org/10.1038/s41467-022-29915-z
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 11

Abstract

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Three covalent hybrid inhibitors of SARS-CoV-2 main protease (Mpro) have been designed and compared to Pfizer’s nirmatrelvir (PF-07321332), providing atomic and thermodynamic details of their binding to the enzyme, and antiviral potency.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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