Profiling of coronaviral Mpro and enteroviral 3Cpro specificity provides a framework for the development of broad‐spectrum antiviral compounds

The main protease from coronaviruses and the 3C protease from enteroviruses play a crucial role in processing viral polyproteins, making them attractive targets for the development of antiviral agents. In this study, we employed a combinatorial chemistry approach—HyCoSuL—to compare the substrate spe...

Full description

Saved in:
Bibliographic Details
Published in:Protein science 2024-09, Vol.33 (9), p.e5139-n/a
Main Authors: Rut, Wioletta, Groborz, Katarzyna, Sun, Xinyuanyuan, Hilgenfeld, Rolf, Drag, Marcin
Format: Article
Language:English
Subjects:
Amino acids
Antiviral agents
Antiviral drugs
Chemical activity
Combinatorial analysis
Combinatorial chemistry
Coronaviridae
Coronaviruses
COVID-19
Enteroviruses
Polyproteins
Protease
Severe acute respiratory syndrome coronavirus 2
Substrate inhibition
Substrate specificity
Viral diseases
viral proteases
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The main protease from coronaviruses and the 3C protease from enteroviruses play a crucial role in processing viral polyproteins, making them attractive targets for the development of antiviral agents. In this study, we employed a combinatorial chemistry approach—HyCoSuL—to compare the substrate specificity profiles of the main and 3C proteases from alphacoronaviruses, betacoronaviruses, and enteroviruses. The obtained data demonstrate that coronavirus Mpros exhibit overlapping substrate specificity in all binding pockets, whereas the 3Cpro from enterovirus displays slightly different preferences toward natural and unnatural amino acids at the P4‐P2 positions. However, chemical tools such as substrates, inhibitors, and activity‐based probes developed for SARS‐CoV‐2 Mpro can be successfully applied to investigate the activity of the Mpro from other coronaviruses as well as the 3Cpro from enteroviruses. Our study provides a structural framework for the development of broad‐spectrum antiviral compounds.
ISSN:0961-8368
1469-896X
1469-896X
DOI:10.1002/pro.5139