Evidence map›Paper›PMID 34544279›Full record

ArticlemBio2021

SARS-CoV-2 Nsp5 Demonstrates Two Distinct Mechanisms Targeting RIG-I and MAVS To Evade the Innate Immune Response.

Yongzhen Liu, Chao Qin, Youliang Rao, Chau Ngo, Joshua J Feng, Jun Zhao, Shu Zhang, Ting-Yu Wang, Jessica Carriere, Ali Can Savas and 9 more

Abstract read
In one paragraph

Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

90 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Review
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  10. Review
  11. Defective RNA Polymerase III sensing of mitochondrial DNA in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  12. Host Responses to SARS-CoV-2 with an Emphasis on Cytokines.International journal of molecular sciences · 2026
    Review
  13. Cellular sensor DAP5 decodesFrontiers in immunology · 2026
    Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article

30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Yongzhen LiuSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Chao QinSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Youliang RaoSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Chau NgoDepartment of Chemistry, Dornsife College of Arts, Letters, and Sciences, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Joshua J FengDepartment of Chemistry, Dornsife College of Arts, Letters, and Sciences, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Jun ZhaoSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Shu ZhangSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Ting-Yu WangSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Jessica CarriereSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Ali Can SavasSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Mehrnaz ZarinfarSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Stephanie RiceSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Hanging YangMolecular and Computational Biology Section, University of Southern California, Los Angeles, California, USA.
Weiming YuanDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, Los Angeles, California, USA.
Julio A CamareroDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Jianhua YuDepartment of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, California, USA.
Xiaojiang S ChenMolecular and Computational Biology Section, University of Southern California, Los Angeles, California, USA.
Chao ZhangDepartment of Chemistry, Dornsife College of Arts, Letters, and Sciences, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.
Pinghui FengSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern Californiagrid.42505.36, Los Angeles, California, USA.ORCID 0000-0002-8494-0205

Funding

The Tumor Microenvironmental Barrier to Effective Viral OncolysisP01CA163205 · NCI · OHIO STATE UNIVERSITY · PI KEITH LLOYD LIGON · 2013 to 2026
$26.0M
Exploring roles of protein deamidation in oral inflammationR35DE027556 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEN, CASEY · 2017 to 2020
$4.1M
Targeting an immune kinase to purge KSHV latent infectionR01DE026003 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEN, CASEY, ZHANG, CHAO · 2016 to 2020
$3.4M
Using the Ultrastable Cyclotide Scaffold to Modulate Protein-protein InteractionsR35GM132072 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CAMARERO, JULIO A · 2019 to 2023
$2.3M
Characterizing and Targeting the Novel IL-15- AKT-XBP1s Pathway in NK CellsR01CA247550 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI YU, JIANHUA · 2020 to 2024
$2.2M
Elucidate and Modulate Cell Signaling in NK Cells for Glioma TreatmentR01AI129582 · NIAID · OHIO STATE UNIVERSITY · PI YU, JIANHUA · 2017 to 2021
$2.1M
NFAT activation in kGPCR tumorigenesisR01CA221521 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FENG, PINGHUI · 2017 to 2021
$1.9M
Overcoming Barriers of Virotherapy by Next-Generation oHSV Expressing E-CadherinR01NS106170 · NINDS · OHIO STATE UNIVERSITY · PI YU, JIANHUA · 2018 to 2023
$1.9M
Phase 1 Evaluation of Enhanced Natural Killer Cells as a Treatment Strategy in Non-Small cell Lung Cancer Patients Refractory to PD-1/PD-L1 Immune Checkpoint InhibitorsR01CA266457 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI VILLALONA, MIGUEL A, YU, JIANHUA · 2022 to 2025
$1.8M
Post-Translational Events Underlying the KSHV vGPCR PathogenesisR01CA134241 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI FENG, PINGHUI · 2009 to 2013
$1.6M
CBI: Chemistry Biology InterfaceT32GM118289 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FORSBURG, SUSAN L · 2016 to 2020
$1.2M
NCI NIH HHS P01 CA163205NCI NIH HHS R01 CA134241NCI NIH HHS R01 CA221521NCI NIH HHS R01 CA247550NCI NIH HHS R01 CA266457NIAID NIH HHS R01 AI129582NIDCR NIH HHS R01 DE026003NIDCR NIH HHS R35 DE027556NIGMS NIH HHS R35 GM132072NIGMS NIH HHS T32 GM118289NINDS NIH HHS R01 NS106170
6 · The paper itself

Abstract

Newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic with astonishing mortality and morbidity. The high replication and transmission of SARS-CoV-2 are remarkably distinct from those of previous closely related coronaviruses, and the underlying molecular mechanisms remain unclear. The innate immune defense is a physical barrier that restricts viral replication. We report here that the SARS-CoV-2 Nsp5 main protease targets RIG-I and mitochondrial antiviral signaling (MAVS) protein via two distinct mechanisms for inhibition. Specifically, Nsp5 cleaves off the 10 most-N-terminal amino acids from RIG-I and deprives it of the ability to activate MAVS, whereas Nsp5 promotes the ubiquitination and proteosome-mediated degradation of MAVS. As such, Nsp5 potently inhibits interferon (IFN) induction by double-stranded RNA (dsRNA) in an enzyme-dependent manner. A synthetic small-molecule inhibitor blunts the Nsp5-mediated destruction of cellular RIG-I and MAVS and processing of SARS-CoV-2 nonstructural proteins, thus restoring the innate immune response and impeding SARS-CoV-2 replication. This work offers new insight into the immune evasion strategy of SARS-CoV-2 and provides a potential antiviral agent to treat CoV disease 2019 (COVID-19) patients.

Indexed as

A549 CellsAdaptor Proteins, Signal TransducingAnimalsCaco-2 CellsCoronavirus 3C ProteasesDEAD Box Protein 58Enzyme-Linked Immunosorbent AssayHCT116 CellsHEK293 CellsHumansImmunity, InnateImmunoblottingInterferon Type IMiceReceptors, ImmunologicReverse Transcriptase Polymerase Chain Reaction3C-like proteinase, SARS-CoV-2Adaptor Proteins, Signal TransducingCoronavirus 3C ProteasesDEAD Box Protein 58Interferon Type IMAVS protein, humanReceptors, ImmunologicRIGI protein, humanE3 ligaseMAVSNsp5proteaseRIG-ISARS-CoV-2small-molecule inhibitor

Identifiers

PMID34544279
PMCPMC8546575

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Registered trials

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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.