ArticleNature communications2021
Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 129 citations in OpenAlex.
- Substrate-Selective Inhibition of the SARS-CoV-2 Papain-Like Protease: Inhibition of Hydrolysis of Human Over Viral Substrates.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Viral protease-mediated polyprotein processing in human astroviruses.Npj viruses · 2026Article
- Unbiased cleavage site prediction uncovers viral antagonism of host innate immunity by SARS-CoV-2 3C-like protease.JCI insight · 2026Article
- Integrative multi-omics framework for causal gene discovery in Long COVID.PLoS computational biology · 2025Article
- Proteolytic profiling of human plasma reveals an immunoactive complement C3 fragment.The EMBO journal · 2025Article
- Profiling the proteome-wide selectivity of diverse electrophiles.Nature chemistry · 2025Article
- Employing complementary fractionation-based N-terminomics approaches enhances the identification of legumain cleavage events in naïve and inflamed colon tissue.Protein science : a publication of the Protein Society · 2025Article
- The main protease (MCommunications biology · 2025Article
- The coronavirus 3CL protease: Unveiling its complex host interactions and central role in viral pathogenesis.Virologica Sinica · 2025Review
- Identification of SARS-CoV-2 Main Protease Cleavage Sites in Bovine β-Casein.International journal of molecular sciences · 2025Article
- A yeast-based reverse genetics system to generate HCoV-OC43 reporter viruses encoding an eighth subgenomic RNA.Journal of virology · 2025Article
- Recognition and cleavage of human tRNA methyltransferase TRMT1 by the SARS-CoV-2 main protease.eLife · 2025Article
- Replication differences of SARS-CoV-2 lineages may arise from unique RNA replication characteristics and nucleocapsid protein expression.Frontiers in cellular and infection microbiology · 2025Article
- Emergence of SARS-CoV-2 subgenomic RNAs that enhance viral fitness and immune evasion.PLoS biology · 2025Article
- Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic.Nature microbiology · 2025Article
- Article
- Identification of the proteolytic signature in CVB3-infected cells.Journal of virology · 2024Article
- Leveraging a self-cleaving peptide for tailored control in proximity labeling proteomics.Cell reports methods · 2024Article
- Article
- Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease.eLife · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
Abstract
SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass spectrometry to identify protein neo-N-termini generated through protease activity. We identify previously unknown cleavage sites in multiple viral proteins, including major antigens S and N: the main targets for vaccine and antibody testing efforts. We discover significant increases in cellular cleavage events consistent with cleavage by SARS-CoV-2 main protease, and identify 14 potential high-confidence substrates of the main and papain-like proteases. We show that siRNA depletion of these cellular proteins inhibits SARS-CoV-2 replication, and that drugs targeting two of these proteins: the tyrosine kinase SRC and Ser/Thr kinase MYLK, show a dose-dependent reduction in SARS-CoV-2 titres. Overall, our study provides a powerful resource to understand proteolysis in the context of viral infection, and to inform the development of targeted strategies to inhibit SARS-CoV-2 and treat COVID-19.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.