ArticlePLoS pathogens2018
The papain-like protease determines a virulence trait that varies among members of the SARS-coronavirus species.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Computational drug discovery and repurposing for the treatment of COVID-19: A systematic review.Bioorganic chemistry · 2021Pooled it
- Bioprinted Four-Cell-Type Lung Model for Viral Infection Studies Under Air-Liquid Interface Conditions.International journal of molecular sciences · 2025Article
- Deubiquitinating activity of SARS-CoV-2 papain-like protease does not influence virus replication or innate immune responses in vivo.PLoS pathogens · 2024Article
- The role of IBV PL1pro in virus replication and suppression of host innate immune responses.BMC veterinary research · 2023Article
- Cellular Assays for Dynamic Quantification of Deubiquitinase Activity and Inhibition.Journal of molecular biology · 2023Article
- Protease inhibitors fromHeliyon · 2023Article
- Engineering potent live attenuated coronavirus vaccines by targeted inactivation of the immune evasive viral deubiquitinase.Nature communications · 2023Article
- Screening and identification of potential MERS-CoV papain-like protease (PLpro) inhibitors; Steady-state kinetic and Molecular dynamic studies.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- SARS-CoV-2 3CLpro whole human proteome cleavage prediction and enrichment/depletion analysis.Computational biology and chemistry · 2022Article
- Molecular dynamics simulation approach for discovering potential inhibitors against SARS-CoV-2: A structural review.Journal of molecular liquids · 2022Review
- Airway epithelial interferon response to SARS-CoV-2 is inferior to rhinovirus and heterologous rhinovirus infection suppresses SARS-CoV-2 replication.Scientific reports · 2022Article
- Exploring naphthyl derivatives as SARS-CoV papain-like protease (PLpro) inhibitors and its implications in COVID-19 drug discovery.Molecular diversity · 2022Article
- Structural and Biochemical Characterization of Porcine Epidemic Diarrhea Virus Papain-Like Protease 2.Journal of virology · 2022Article
- Article
- Dysregulated Interferon Response and Immune Hyperactivation in Severe COVID-19: Targeting STATs as a Novel Therapeutic Strategy.Frontiers in immunology · 2022Review
- Article
- SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species.Emerging microbes & infections · 2021Article
- Structure of the multiple functional domains from coronavirus nonstructural protein 3.Emerging microbes & infections · 2021Article
- Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence.Viruses · 2021Article
- Functional comparison of MERS-coronavirus lineages reveals increased replicative fitness of the recombinant lineage 5.Nature communications · 2021Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
SARS-coronavirus (CoV) is a zoonotic agent derived from rhinolophid bats, in which a plethora of SARS-related, conspecific viral lineages exist. Whereas the variability of virulence among reservoir-borne viruses is unknown, it is generally assumed that the emergence of epidemic viruses from animal reservoirs requires human adaptation. To understand the influence of a viral factor in relation to interspecies spillover, we studied the papain-like protease (PLP) of SARS-CoV. This key enzyme drives the early stages of infection as it cleaves the viral polyprotein, deubiquitinates viral and cellular proteins, and antagonizes the interferon (IFN) response. We identified a bat SARS-CoV PLP, which shared 86% amino acid identity with SARS-CoV PLP, and used reverse genetics to insert it into the SARS-CoV genome. The resulting virus replicated like SARS-CoV in Vero cells but was suppressed in IFN competent MA-104 (3.7-fold), Calu-3 (2.6-fold) and human airway epithelial cells (10.3-fold). Using ectopically-expressed PLP variants as well as full SARS-CoV infectious clones chimerized for PLP, we found that a protease-independent, anti-IFN function exists in SARS-CoV, but not in a SARS-related, bat-borne virus. This PLP-mediated anti-IFN difference was seen in primate, human as well as bat cells, thus independent of the host context. The results of this study revealed that coronavirus PLP confers a variable virulence trait among members of the species SARS-CoV, and that a SARS-CoV lineage with virulent PLPs may have pre-existed in the reservoir before onset of the epidemic.
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Registered trials
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