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Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential

Medicine and Health

Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential

B. Meyer, J. Chiaravalli, et al.

This groundbreaking study by Bjoern Meyer and colleagues uncovers novel cleavage sites in SARS-CoV-2 proteins S and N using mass spectrometry. The research highlights potential therapeutic targets and demonstrates how targeting specific substrates inhibits SARS-CoV-2 replication. A must-listen for those interested in advancing COVID-19 research and treatments!

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Playback language: English
Abstract
This study investigates proteolytic cleavage of viral and cellular proteins during SARS-CoV-2 infection using mass spectrometry. It identifies novel cleavage sites in viral proteins S and N, key targets for vaccine and antibody development. The study also reveals increased cellular cleavage events consistent with SARS-CoV-2 main protease activity, identifying 14 potential substrates. siRNA depletion of these substrates inhibits SARS-CoV-2 replication, and drugs targeting SRC and MYLK reduce viral titres. This research provides valuable insights into SARS-CoV-2 proteolysis and potential therapeutic targets.
Publisher
Nature Communications
Published On
Sep 21, 2021
Authors
Bjoern Meyer, Jeanne Chiaravalli, Stacy Gellenoncourt, Philip Brownridge, Dominic P. Bryne, Leonard A. Daly, Arturas Grauslys, Marius Walter, Fabrice Agou, Lisa A. Chakrabarti, Charles S. Craik, Claire E. Eyers, Patrick A. Eyers, Yann Gambin, Andrew R. Jones, Emma Sierecki, Eric Verdin, Marco Vignuzzi, Edward Emmott
Tags
SARS-CoV-2
proteolytic cleavage
mass spectrometry
therapeutic targets
viral replication
cleavage sites
substrates

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