ArticleEmerging microbes & infections2021
SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species.
Article in Emerging microbes & infections, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers, 1 of them a synthesis that pooled it.
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Who cites it
184 citing papers in PubMed, 1 synthesis or guideline pooled it, 284 citations in OpenAlex.
- Newly Emerged Antiviral Strategies for SARS-CoV-2: From Deciphering Viral Protein Structural Function to the Development of Vaccines, Antibodies, and Small Molecules.International journal of molecular sciences · 2022Pooled it
- Sarbecoviruses Suppress Innate Immunity by Recruiting PPM1A to Modulate STAT2 and ORF9b Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 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
- Host OTUB2 and viral PLpro stabilize NSP8 to promote SARS-CoV-2 replication.Virologica Sinica · 2026Article
- Cleavage of TOM1 by the SARS-CoV-2 main protease NSP5 prevents autophagic degradation of viral envelope.Journal of virology · 2026Article
- SARS-CoV-2 3CL protease interaction with host factors - identifying novel drug targets.Archives of virology · 2026Review
- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
- The seven human coronavirus main proteases exhibit differential modulation of NF-κB suppression via TAB1 cleavage.Communications biology · 2026Article
- NLR Inflammasomes in Viral Infections: From Molecular Mechanisms to Therapeutic Interventions.Viruses · 2026Review
- Redundant and distinct mechanisms suppress innate immune activation during SARS-CoV-2 infection.PLoS biology · 2026Article
- Article
- SARS-CoV-2 nonstructural protein 3 remodels the phosphorylation of target proteins via protein-protein interactions.Microbiology spectrum · 2026Article
- Entry, replication and innate immunity evasion of BANAL-236, a SARS-CoV-2-related bat virus, in Rhinolophus and human cells.PLoS pathogens · 2026Article
- Unbiased cleavage site prediction uncovers viral antagonism of host innate immunity by SARS-CoV-2 3C-like protease.JCI insight · 2026Article
- Porcine Deltacoronavirus Nsp13 Suppresses the Assembly of the MAVS-TBK1-IRF3 Complex and IRF9 Nuclear Translocation.Transboundary and emerging diseases · 2026Article
- Cellular sensor DAP5 decodesFrontiers in immunology · 2026Article
- SARS-CoV-2 variants: biology, pathogenicity, immunity and control.Nature reviews. Microbiology · 2026Review
- Proteomic Analysis of COVID-19 Infection.Advances in experimental medicine and biology · 2026Article
- SARS-CoV-2-host and interactions: the dual roles of E3 ubiquitin ligases and ubiquitin-like modification mechanisms in viral infection.Frontiers in immunology · 2026Review
- Human coronavirus 3CL protease manipulates host protein STIM1 to facilitate immune evasion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
124 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The genome of SARS-CoV-2 encodes two viral proteases (NSP3/papain-like protease and NSP5/3C-like protease) that are responsible for cleaving viral polyproteins during replication. Here, we discovered new functions of the NSP3 and NSP5 proteases of SARS-CoV-2, demonstrating that they could directly cleave proteins involved in the host innate immune response. We identified 3 proteins that were specifically and selectively cleaved by NSP3 or NSP5: IRF-3, and NLRP12 and TAB1, respectively. Direct cleavage of IRF3 by NSP3 could explain the blunted Type-I IFN response seen during SARS-CoV-2 infections while NSP5 mediated cleavage of NLRP12 and TAB1 point to a molecular mechanism for enhanced production of cytokines and inflammatory responThe genome of SARS-CoV-2 encodes two viral proteases (NSP3/papain-like protease and NSP5/3C-like protease) that are responsible for cleaving viral polyproteins during replication. Here, we discovered new functions of the NSP3 and NSP5 proteases of SARS-CoV-2, demonstrating that they could directly cleave proteins involved in the host innate immune response. We identified 3 proteins that were specifically and selectively cleaved by NSP3 or NSP5: IRF-3, and NLRP12 and TAB1, respectively. Direct cleavage of IRF3 by NSP3 could explain the blunted Type-I IFN response seen during SARS-CoV-2 infections while NSP5 mediated cleavage of NLRP12 and TAB1 point to a molecular mechanism for enhanced production of cytokines and inflammatory response observed in COVID-19 patients. We demonstrate that in the mouse NLRP12 protein, one of the recognition site is not cleaved in our
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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 OpenQuestion graph.