The coronavirus 3CL protease: Unveiling its complex host interactions and central role in viral pathogenesis
Yecheng Zhang, Xinlei Ji, Dan Huang, Gen Lu, Xinwen Chen
Virologica Sinica, doi:10.1016/j.virs.2025.07.002
The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.
CONFLICT OF INTEREST The authors declare that they have no conflict of interest. Prof. Xinwen Chen is an editorial board member for Virologica Sinica and was not involved in the editorial review or the decision to publish this article.
References
Aglietti, Estevez, Gupta, Ramirez, Liu et al., GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes, Proc. Natl. Acad. Sci. U. S. A
Anand, Palm, Mesters, Siddell, Ziebuhr et al., Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain, EMBO J
Bacha, Barrila, Velazquez-Campoy, Leavitt, Freire, Identification of novel inhibitors of the SARS coronavirus main protease 3CLpro, Biochemistry
Bergsbaken, Fink, Cookson, Pyroptosis: host cell death and inflammation, Nat. Rev. Microbiol
Broz, Pelegrín, Shao, The gasdermins, a protein family executing cell death and inflammation, Nat. Rev. Immunol
Cao, Ding, Xu, Li, Zheng et al., Small-molecule anti-COVID-19 drugs and a focus on China's homegrown mindeudesivir (VV116), Front. Med
Chen, Li, Guo, Xu, Zhou et al., SARS-CoV-2 nsp5 exhibits stronger catalytic activity and interferon antagonism than its SARS-CoV ortholog, J. Virol
Chen, Tian, He, Tian, Han et al., Overview of lethal human coronaviruses, Signal Transduct. Targeted Ther
Chen, Tian, Li, Kang, Zhang et al., Feline infectious peritonitis virus Nsp5 inhibits type I interferon production by cleaving NEMO at multiple sites, Viruses
Chen, Yu, Kuo, Min, Chen et al., Overview of antiviral drug candidates targeting coronaviral 3C-like main proteases, FEBS J
Chen, Zhang, Hu, Chen, Jiang et al., Residues on the dimer interface of SARS coronavirus 3C-like protease: dimer stability characterization and enzyme catalytic activity analysis, J. Biochem
Chen, Zhu, Qiu, Ge, Zheng et al., Prediction of coronavirus 3Clike protease cleavage sites using machine-learning algorithms, Virol. Sin
Choi, Lee, Kim, Park, Kim et al., HDAC6 regulates cellular viral RNA sensing by deacetylation of RIG-I, EMBO J
Chow, Gale, Loo, RIG-I and other RNA sensors in antiviral immunity, Annu. Rev. Immunol
Coombs, Zamoshnikova, Holley, Maddugoda, Teo et al., NLRP12 interacts with NLRP3 to block the activation of the human NLRP3 inflammasome, Sci. Signal
Crooks, Hon, Chandonia, Brenner, WebLogo: a sequence logo generator, Genome Res
Dai, Mottaghinia, Olson, Geissler, Etienne et al., Recognition and cleavage of human tRNA methyltransferase TRMT1 by the SARS-CoV-2 main protease, eLife
De Castro, Cariste, Almeida, Sasahara, Silva et al., Potential protective role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in COVID-19, Front. Cell. Infect. Microbiol
Ding, Wang, Liu, She, Sun et al., Pore-forming activity and structural autoinhibition of the gasdermin family, Nature
Duan, Wang, Yuan, Yang, Structural biology of SARS-CoV-2 M(pro) and drug discovery, Curr. Opin. Struct. Biol
Evavold, Ruan, Tan, Xia, Wu et al., The pore-forming protein Gasdermin D regulates interleukin-1 secretion from living macrophages, Immunity
Freeman, Swartz, Targeting the NLRP3 inflammasome in severe COVID-19, Front. Immunol
Fung, Siu, Lin, Yeung, Jin, SARS-CoV-2 main protease suppresses type I interferon production by preventing nuclear translocation of phosphorylated IRF3, Int. J. Biol. Sci
Gordon, Jang, Bouhaddou, Xu, Obernier et al., A SARS-CoV-2 protein interaction map reveals targets for drug repurposing, Nature
Gordon, Tchesnokov, Feng, Porter, Gotte, The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus, J. Biol. Chem
He, Ji, Hale, Cheung, Ahmed et al., Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race, Hepatology
Hsu, Kuo, Chang, Chang, Chou et al., Mechanism of the maturation process of SARS-CoV 3CL protease, J. Biol. Chem
Hu, Xiong, Zhu, Zhang, Zhang et al., The SARS-CoV-2 main protease (M pro ): structure, function, and emerging therapies for COVID-19, MedComm
Huang, Lei, Zhao, Qin, Li et al., Porcine deltacoronavirus nsp5 antagonizes type I interferon signaling by cleaving IFIT3, J. Virol
Huang, Zhao, Lei, Zhang, Li et al., Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A, Front. Immunol
Jochmans, Liu, Donckers, Stoycheva, Boland et al., The substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro are selected by a protease inhibitor in vitro and confer resistance to nirmatrelvir, mBio
Ju, Wang, Wang, Ren, Yu et al., SARS-CoV-2 main protease cleaves MAGED2 to antagonize host antiviral defense, mBio
Kesheh, Hosseini, Soltani, Zandi, An overview on the seven pathogenic human coronaviruses, Rev. Med. Virol
Kiemer, Lund, Brunak, Blom, Coronavirus 3CLpro proteinase cleavage sites: possible relevance to SARS virus pathology, BMC Bioinf
Koudelka, Boger, Henkel, Sch€ Onherr, Krantz et al., N-terminomics for the identification of in vitro substrates and cleavage site specificity of the SARS-CoV-2 main protease, Proteomics
Kumar, Grams, Bloom, Toth, Signaling pathway reporter screen with SARS-CoV-2 proteins identifies nsp5 as a repressor of p53 activity, Viruses
Lamark, Svenning, Johansen, Regulation of selective autophagy: the p62/SQSTM1 paradigm, Essays Biochem
Lamb, Yoshimori, Tooze, The autophagosome: origins unknown, biogenesis complex, Nat. Rev. Mol. Cell Biol
Lear, Boudreau � A, Lockwood, Chu, Camarco et al., E3 ubiquitin ligase ZBTB25 suppresses beta coronavirus infection through ubiquitination of the main viral protease MPro, J. Biol. Chem
Levine, Kroemer, Autophagy in the pathogenesis of disease, Cell
Levine, Mizushima, Virgin, Autophagy in immunity and inflammation, Nature
Lewnard, Mclaughlin, Malden, Hong, Puzniak et al., Effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system, Lancet Infect. Dis
Li, Chen, Zhao, Liu, Kong et al., Cleavage of the selective autophagy receptor NBR1 by the PDCoV main protease NSP5 impairs autophagic degradation of the viral envelope protein, Autophagy
Li, Duan, Qiu, Fang, Fang et al., HDAC6 degrades nsp8 of porcine deltacoronavirus through deacetylation and ubiquitination to inhibit viral replication, J. Virol
Li, Fang, Duan, Chen, Fang et al., Porcine deltacoronavirus infection cleaves HDAC2 to attenuate its antiviral activity, J. Virol
Li, Qiao, You, Zong, Peng et al., SARS-CoV-2 Nsp5 activates NF-κB pathway by upregulating SUMOylation of MAVS, Front. Immunol
Li, Xiao, Yang, Guo, Zhou et al., Cleavage of HDAC6 to dampen its antiviral activity by nsp5 is a common strategy of swine enteric coronaviruses, J. Virol
Li, Yu, Huang, Chen, Ren et al., SARS-CoV-2 SUD2 and Nsp5 conspire to boost apoptosis of respiratory epithelial cells via an augmented interaction with the G-quadruplex of BclII, mBio
Liu, Bai, Zhang, Gao, Liu et al., SARS-CoV-2 N protein antagonizes stress granule assembly and IFN production by interacting with G3BPs to facilitate viral replication, J. Virol
Liu, Qin, Rao, Ngo, Feng et al., SARS-CoV-2 Nsp5 demonstrates two distinct mechanisms targeting RIG-I and MAVS to evade the innate immune response, mBio
Liu, Wang, Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines, J Genet Genomics
Lu, Zhou, SARS-CoV-2 main protease Nsp5 cleaves and inactivates human tRNA methyltransferase TRMT1, J. Mol. Cell Biol
Luo, Moussa, Lopez-Orozco, Felix-Lopez, Ishida et al., Identification of human host substrates of the SARS-CoV-2 M(pro) and PL(pro) using subtiligase N-terminomics, ACS Infect. Dis
Ma, Yoon, Richardson, Jülich, Blenis, SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs, Cell
Marti� Añez-Vendrell, Bloeme-Ter, Horst, Hutchinson, Guy et al., Human coronavirus 229E infection inactivates pyroptosis executioner gasdermin D but ultimately leads to lytic cell death partly mediated by Gasdermin E, Viruses
Meyer, Chiaravalli, Gellenoncourt, Brownridge, Bryne et al., Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential, Nat. Commun
Miczi, Golda, Kunkli, Nagy, Tozser et al., Identification of host cellular protein substrates of SARS-COV-2 main protease, Int. J. Mol. Sci
Mizushima, Yoshimori, Ohsumi, The role of Atg proteins in autophagosome formation, Annu. Rev. Cell Dev. Biol
Moustaqil, Ollivier, Chiu, Van Tol, Rudolffi-Soto et al., SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species, Emerg. Microb. Infect
Nikolic, Civas, Lama, Lagaudri� Ere-Gesbert, Blondel, Rabies virus infection induces the Formation of stress granules closely connected to the viral factories, PLoS Pathog
Pablos, Machado, De, Mohamud, Kappelhoff et al., Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CL(pro) substrate degradome, Cell Rep
Park, Lee, Jeong, Kweon, Shin et al., A gain-of-function cleavage of TonEBP by coronavirus NSP5 to suppress IFN-β expression, Cells
Plan� Es, Pinilla, Santoni, Hessel, Passemar et al., Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells, Mol. Cell
Rehwinkel, Gack, RIG-I-like receptors: their regulation and roles in RNA sensing, Nat. Rev. Immunol
Schroder, Tschopp, The inflammasomes, Cell
Shen, Guo, Li, Zhang, Tang et al., SARS-CoV-2 and oncolytic EV-D68-encoded proteases differentially regulate pyroptosis, J. Virol
Shi, Lv, Wang, Xu, Xu et al., Coronaviruses Nsp5 antagonizes porcine gasdermin Dmediated pyroptosis by cleaving pore-forming p30 fragment, mBio
Shibutani, Yoshimori, A current perspective of autophagosome biogenesis, Cell Res
Song, Wang, Abbas, Li, Cui et al., The main protease of SARS-CoV-2 cleaves histone deacetylases and DCP1A, attenuating the immune defense of the interferon-stimulated genes, J. Biol. Chem
Stark, Darnell, The JAK-STAT pathway at twenty, Immunity
Taabazuing, Griswold, Bachovchin, The NLRP1 and CARD8 inflammasomes, Immunol. Rev
Tsu, Agarwal, Gokhale, Kulsuptrakul, Ryan et al., Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome, PLoS Biol
Tziortzouda, Van Den, Bosch, Hirth, Triad of TDP43 control in neurodegeneration: autoregulation, localization and aggregation, Nat. Rev. Neurosci
Van Huizen, Vendrell, De Gruyter, Boomaars-Van Der Zanden, Van Der Meer et al., The main protease of Middle East respiratory syndrome Coronavirus induces cleavage of mitochondrial antiviral signaling protein to antagonize the innate immune response, Viruses
Van Opdenbosch, Lamkanfi, Caspases in cell death, inflammation, and disease, Immunity
Wang, Fang, Shi, Zhang, Gao et al., Porcine epidemic diarrhea virus 3C-like protease regulates its interferon antagonism by cleaving NEMO, J. Virol
Wang, Liu, Li, Hao, Roles of p53-mediated host-virus interaction in coronavirus infection, Int. J. Mol. Sci
Webber, Okano, Little, Reich, Xin et al., Tripeptide aldehyde inhibitors of human rhinovirus 3C protease: design, synthesis, biological evaluation, and cocrystal structure solution of P1 glutamine isosteric replacements, J. Med. Chem
Woo, Lau, Chu, Chan, Tsoi et al., Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia, J. Virol
Wu, Li, Tian, Yan, Pan et al., Broad antagonism of coronaviruses nsp5 to evade the host antiviral responses by cleaving POLDIP3, PLoS Pathog
Wu, Ma, Zhuang, Cai, Zhao et al., Main protease of SARS-CoV-2 serves as a bifunctional molecule in restricting type I interferon antiviral signaling, Signal Transduct. Targeted Ther
Xiong, Li, Li, Huang, Dong et al., Human TRMT1 catalyzes m(2)G or m(2)(2)G formation on tRNAs in a substrate-dependent manner, Sci. China Life Sci
Xiong, Su, Zhao, Xie, Shao et al., What coronavirus 3C-like protease tells us: from structure, substrate selectivity, to inhibitor design, Med. Res. Rev
Yang, Li, Wang, Li, Zhang et al., The SARS-CoV-2 main protease induces neurotoxic TDP-43 cleavage and aggregates, Signal Transduct. Targeted Ther
Yang, Ru, Ren, Bai, Wei et al., G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response, Cell Death Dis
Yang, Yang, Ding, Liu, Lou et al., The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor, Proc. Natl. Acad. Sci. USA
Yuan, Ma, Xie, Li, Su et al., The role of cell death in SARS-CoV-2 infection, Signal Transduct. Targeted Ther
Zhang, Ji, Huang, Lu, Chen, The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D, Virol. Sin
Zhang, Kandwal, Fayne, Stevenson, MERS-CoV-nsp5 expression in human epithelial BEAS 2b cells attenuates type I interferon production by inhibiting IRF3 nuclear translocation, Cell. Mol. Life Sci
Zhang, Liu, Xu, Li, Lu, Cleavage of the selective autophagy receptor SQSTM1/p62 by the SARS-CoV-2 main protease NSP5 prevents the autophagic degradation of viral membrane proteins, Mol Biomed
Zhang, Wang, Cheng, Protease cleavage of RNF20 facilitates coronavirus replication via stabilization of SREBP1, Proc. Natl. Acad. Sci. U. S. A
Zheng, Deng, Han, Zhuang, Xu et al., SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules, Signal Transduct. Targeted Ther
Zheng, Zhao, Yang, Feng, Xin et al., Small-molecule antiviral treatments for COVID-19: a systematic review and network meta-analysis, Int. J. Antimicrob. Agents
Zhou, Feng, Yang, Wei, Fan et al., E3 ubiquitin ligase FBXO22 inhibits SARS-CoV-2 replication via promoting proteasome-dependent degradation of NSP5, J. Med. Virol
Zhou, Gammeltoft, Ryberg, Pham, Tjørnelund et al., Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system, Sci. Adv
Zhou, Liu, Pathak, Wang, Jeong et al., Ubiquitin ligase Parkin regulates the stability of SARS-CoV-2 main protease and suppresses viral replication, ACS Infect. Dis
Zhou, Sun, Wang, Qiu, Yang et al., Deep profiling of potential substrate atlas of porcine epidemic diarrhea virus 3C-like protease, J. Virol
Zhu, Chen, Tian, Zhou, Xu et al., Porcine deltacoronavirus nsp5 cleaves DCP1A to decrease its antiviral activity, J. Virol
Zhu, Fang, Wang, Yang, Chen et al., Porcine deltacoronavirus nsp5 inhibits interferon-β production through the cleavage of NEMO, Virology
Zhu, Wang, Zhou, Pan, Chen et al., Porcine deltacoronavirus nsp5 antagonizes type I interferon signaling by cleaving STAT2, J. Virol
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"year": "2016"
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{
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"author": "Chen",
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"first-page": "437",
"journal-title": "Virol. Sin.",
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"year": "2022"
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{
"DOI": "10.1128/jvi.00037-22",
"article-title": "SARS-CoV-2 nsp5 exhibits stronger catalytic activity and interferon antagonism than its SARS-CoV ortholog",
"author": "Chen",
"doi-asserted-by": "crossref",
"journal-title": "J. Virol.",
"key": "10.1016/j.virs.2025.07.002_bib10",
"volume": "96",
"year": "2022"
},
{
"DOI": "10.3390/v12010043",
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"author": "Chen",
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"first-page": "525",
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"DOI": "10.15252/embj.201592586",
"article-title": "HDAC6 regulates cellular viral RNA sensing by deacetylation of RIG-I",
"author": "Choi",
"doi-asserted-by": "crossref",
"first-page": "429",
"journal-title": "EMBO J.",
"key": "10.1016/j.virs.2025.07.002_bib13",
"volume": "35",
"year": "2016"
},
{
"DOI": "10.1146/annurev-immunol-042617-053309",
"article-title": "RIG-I and other RNA sensors in antiviral immunity",
"author": "Chow",
"doi-asserted-by": "crossref",
"first-page": "667",
"journal-title": "Annu. Rev. Immunol.",
"key": "10.1016/j.virs.2025.07.002_bib14",
"volume": "36",
"year": "2018"
},
{
"DOI": "10.1126/scisignal.abg8145",
"article-title": "NLRP12 interacts with NLRP3 to block the activation of the human NLRP3 inflammasome",
"author": "Coombs",
"doi-asserted-by": "crossref",
"journal-title": "Sci. Signal.",
"key": "10.1016/j.virs.2025.07.002_bib15",
"volume": "17",
"year": "2024"
},
{
"DOI": "10.1101/gr.849004",
"article-title": "WebLogo: a sequence logo generator",
"author": "Crooks",
"doi-asserted-by": "crossref",
"first-page": "1188",
"journal-title": "Genome Res.",
"key": "10.1016/j.virs.2025.07.002_bib16",
"volume": "14",
"year": "2004"
},
{
"DOI": "10.7554/eLife.91168.3",
"article-title": "Recognition and cleavage of human tRNA methyltransferase TRMT1 by the SARS-CoV-2 main protease",
"author": "D'oliviera",
"doi-asserted-by": "crossref",
"first-page": "RP91168",
"journal-title": "eLife",
"key": "10.1016/j.virs.2025.07.002_bib17",
"volume": "12",
"year": "2025"
},
{
"DOI": "10.3389/fcimb.2024.1464581",
"article-title": "Potential protective role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in COVID-19",
"author": "De Castro",
"doi-asserted-by": "crossref",
"journal-title": "Front. Cell. Infect. Microbiol.",
"key": "10.1016/j.virs.2025.07.002_bib18",
"volume": "14",
"year": "2024"
},
{
"DOI": "10.1038/nature18590",
"article-title": "Pore-forming activity and structural autoinhibition of the gasdermin family",
"author": "Ding",
"doi-asserted-by": "crossref",
"first-page": "111",
"journal-title": "Nature",
"key": "10.1016/j.virs.2025.07.002_bib19",
"volume": "535",
"year": "2016"
},
{
"DOI": "10.1016/j.sbi.2023.102667",
"article-title": "Structural biology of SARS-CoV-2 M(pro) and drug discovery",
"author": "Duan",
"doi-asserted-by": "crossref",
"journal-title": "Curr. Opin. Struct. Biol.",
"key": "10.1016/j.virs.2025.07.002_bib20",
"volume": "82",
"year": "2023"
},
{
"DOI": "10.1016/j.immuni.2017.11.013",
"article-title": "The pore-forming protein Gasdermin D regulates interleukin-1 secretion from living macrophages",
"author": "Evavold",
"doi-asserted-by": "crossref",
"first-page": "35",
"journal-title": "Immunity",
"key": "10.1016/j.virs.2025.07.002_bib21",
"volume": "48",
"year": "2018"
},
{
"DOI": "10.3389/fimmu.2020.01518",
"article-title": "Targeting the NLRP3 inflammasome in severe COVID-19",
"author": "Freeman",
"doi-asserted-by": "crossref",
"first-page": "1518",
"journal-title": "Front. Immunol.",
"key": "10.1016/j.virs.2025.07.002_bib22",
"volume": "11",
"year": "2020"
},
{
"DOI": "10.7150/ijbs.59943",
"article-title": "SARS-CoV-2 main protease suppresses type I interferon production by preventing nuclear translocation of phosphorylated IRF3",
"author": "Fung",
"doi-asserted-by": "crossref",
"first-page": "1547",
"journal-title": "Int. J. Biol. Sci.",
"key": "10.1016/j.virs.2025.07.002_bib23",
"volume": "17",
"year": "2021"
},
{
"DOI": "10.1074/jbc.AC120.013056",
"article-title": "The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus",
"author": "Gordon",
"doi-asserted-by": "crossref",
"first-page": "4773",
"journal-title": "J. Biol. Chem.",
"key": "10.1016/j.virs.2025.07.002_bib24",
"volume": "295",
"year": "2020"
},
{
"DOI": "10.1038/s41586-020-2286-9",
"article-title": "A SARS-CoV-2 protein interaction map reveals targets for drug repurposing",
"author": "Gordon",
"doi-asserted-by": "crossref",
"first-page": "459",
"journal-title": "Nature",
"key": "10.1016/j.virs.2025.07.002_bib25",
"volume": "583",
"year": "2020"
},
{
"DOI": "10.1002/hep.21267",
"article-title": "Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race",
"author": "He",
"doi-asserted-by": "crossref",
"first-page": "352",
"journal-title": "Hepatology",
"key": "10.1016/j.virs.2025.07.002_bib26",
"volume": "44",
"year": "2006"
},
{
"DOI": "10.1074/jbc.M502577200",
"article-title": "Mechanism of the maturation process of SARS-CoV 3CL protease",
"author": "Hsu",
"doi-asserted-by": "crossref",
"first-page": "31257",
"journal-title": "J. Biol. Chem.",
"key": "10.1016/j.virs.2025.07.002_bib27",
"volume": "280",
"year": "2005"
},
{
"DOI": "10.1002/mco2.151",
"article-title": "The SARS-CoV-2 main protease (Mpro): structure, function, and emerging therapies for COVID-19",
"author": "Hu",
"doi-asserted-by": "crossref",
"journal-title": "MedComm",
"key": "10.1016/j.virs.2025.07.002_bib28",
"volume": "3",
"year": "2022"
},
{
"DOI": "10.1128/jvi.01682-23",
"article-title": "Porcine deltacoronavirus nsp5 antagonizes type I interferon signaling by cleaving IFIT3",
"author": "Huang",
"doi-asserted-by": "crossref",
"journal-title": "J. Virol.",
"key": "10.1016/j.virs.2025.07.002_bib29",
"volume": "98",
"year": "2024"
},
{
"article-title": "Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A",
"author": "Huang",
"journal-title": "Front. Immunol.",
"key": "10.1016/j.virs.2025.07.002_bib30",
"volume": "14",
"year": "2023"
},
{
"DOI": "10.1128/mbio.02815-22",
"article-title": "The substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro are selected by a protease inhibitor in vitro and confer resistance to nirmatrelvir",
"author": "Jochmans",
"doi-asserted-by": "crossref",
"journal-title": "mBio",
"key": "10.1016/j.virs.2025.07.002_bib31",
"volume": "14",
"year": "2023"
},
{
"article-title": "SARS-CoV-2 main protease cleaves MAGED2 to antagonize host antiviral defense",
"author": "Ju",
"journal-title": "mBio",
"key": "10.1016/j.virs.2025.07.002_bib32",
"volume": "14",
"year": "2023"
},
{
"DOI": "10.1002/rmv.2282",
"article-title": "An overview on the seven pathogenic human coronaviruses",
"author": "Kesheh",
"doi-asserted-by": "crossref",
"journal-title": "Rev. Med. Virol.",
"key": "10.1016/j.virs.2025.07.002_bib33",
"volume": "32",
"year": "2022"
},
{
"DOI": "10.1186/1471-2105-5-72",
"article-title": "Coronavirus 3CLpro proteinase cleavage sites: possible relevance to SARS virus pathology",
"author": "Kiemer",
"doi-asserted-by": "crossref",
"first-page": "72",
"journal-title": "BMC Bioinf.",
"key": "10.1016/j.virs.2025.07.002_bib34",
"volume": "5",
"year": "2004"
},
{
"DOI": "10.1002/pmic.202000246",
"article-title": "N-terminomics for the identification of in vitro substrates and cleavage site specificity of the SARS-CoV-2 main protease",
"author": "Koudelka",
"doi-asserted-by": "crossref",
"journal-title": "Proteomics",
"key": "10.1016/j.virs.2025.07.002_bib35",
"volume": "21",
"year": "2021"
},
{
"DOI": "10.3390/v14051039",
"article-title": "Signaling pathway reporter screen with SARS-CoV-2 proteins identifies nsp5 as a repressor of p53 activity",
"author": "Kumar",
"doi-asserted-by": "crossref",
"first-page": "1039",
"journal-title": "Viruses",
"key": "10.1016/j.virs.2025.07.002_bib36",
"volume": "14",
"year": "2022"
},
{
"DOI": "10.1042/EBC20170035",
"article-title": "Regulation of selective autophagy: the p62/SQSTM1 paradigm",
"author": "Lamark",
"doi-asserted-by": "crossref",
"first-page": "609",
"journal-title": "Essays Biochem.",
"key": "10.1016/j.virs.2025.07.002_bib37",
"volume": "61",
"year": "2017"
},
{
"DOI": "10.1038/nrm3696",
"article-title": "The autophagosome: origins unknown, biogenesis complex",
"author": "Lamb",
"doi-asserted-by": "crossref",
"first-page": "759",
"journal-title": "Nat. Rev. Mol. Cell Biol.",
"key": "10.1016/j.virs.2025.07.002_bib38",
"volume": "14",
"year": "2013"
},
{
"DOI": "10.1016/j.jbc.2023.105388",
"article-title": "E3 ubiquitin ligase ZBTB25 suppresses beta coronavirus infection through ubiquitination of the main viral protease MPro",
"author": "Lear",
"doi-asserted-by": "crossref",
"journal-title": "J. Biol. Chem.",
"key": "10.1016/j.virs.2025.07.002_bib39",
"volume": "299",
"year": "2023"
},
{
"DOI": "10.1016/j.cell.2007.12.018",
"article-title": "Autophagy in the pathogenesis of disease",
"author": "Levine",
"doi-asserted-by": "crossref",
"first-page": "27",
"journal-title": "Cell",
"key": "10.1016/j.virs.2025.07.002_bib40",
"volume": "132",
"year": "2008"
},
{
"DOI": "10.1038/nature09782",
"article-title": "Autophagy in immunity and inflammation",
"author": "Levine",
"doi-asserted-by": "crossref",
"first-page": "323",
"journal-title": "Nature",
"key": "10.1016/j.virs.2025.07.002_bib41",
"volume": "469",
"year": "2011"
},
{
"DOI": "10.1016/S1473-3099(23)00118-4",
"article-title": "Effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system",
"author": "Lewnard",
"doi-asserted-by": "crossref",
"first-page": "806",
"journal-title": "Lancet Infect. Dis.",
"key": "10.1016/j.virs.2025.07.002_bib42",
"volume": "23",
"year": "2023"
},
{
"DOI": "10.1080/15548627.2025.2474576",
"article-title": "Cleavage of the selective autophagy receptor NBR1 by the PDCoV main protease NSP5 impairs autophagic degradation of the viral envelope protein",
"author": "Li",
"doi-asserted-by": "crossref",
"first-page": "1507",
"journal-title": "Autophagy",
"key": "10.1016/j.virs.2025.07.002_bib43",
"volume": "21",
"year": "2025"
},
{
"article-title": "SARS-CoV-2 Nsp5 activates NF-κB pathway by upregulating SUMOylation of MAVS",
"author": "Li",
"journal-title": "Front. Immunol.",
"key": "10.1016/j.virs.2025.07.002_bib44",
"volume": "12",
"year": "2021"
},
{
"DOI": "10.1128/mbio.03359-22",
"article-title": "SARS-CoV-2 SUD2 and Nsp5 conspire to boost apoptosis of respiratory epithelial cells via an augmented interaction with the G-quadruplex of BclII",
"author": "Li",
"doi-asserted-by": "crossref",
"journal-title": "mBio",
"key": "10.1016/j.virs.2025.07.002_bib45",
"volume": "14",
"year": "2023"
},
{
"DOI": "10.1128/jvi.00375-23",
"article-title": "HDAC6 degrades nsp8 of porcine deltacoronavirus through deacetylation and ubiquitination to inhibit viral replication",
"author": "Li",
"doi-asserted-by": "crossref",
"journal-title": "J. Virol.",
"key": "10.1016/j.virs.2025.07.002_bib46",
"volume": "97",
"year": "2023"
},
{
"DOI": "10.1128/jvi.01027-22",
"article-title": "Porcine deltacoronavirus infection cleaves HDAC2 to attenuate its antiviral activity",
"author": "Li",
"doi-asserted-by": "crossref",
"journal-title": "J. Virol.",
"key": "10.1016/j.virs.2025.07.002_bib47",
"volume": "96",
"year": "2022"
},
{
"article-title": "Cleavage of HDAC6 to dampen its antiviral activity by nsp5 is a common strategy of swine enteric coronaviruses",
"author": "Li",
"journal-title": "J. Virol.",
"key": "10.1016/j.virs.2025.07.002_bib48",
"volume": "98",
"year": "2024"
},
{
"DOI": "10.1128/jvi.00412-22",
"article-title": "SARS-CoV-2 N protein antagonizes stress granule assembly and IFN production by interacting with G3BPs to facilitate viral replication",
"author": "Liu",
"doi-asserted-by": "crossref",
"journal-title": "J. Virol.",
"key": "10.1016/j.virs.2025.07.002_bib49",
"volume": "96",
"year": "2022"
},
{
"DOI": "10.1016/j.jgg.2020.02.001",
"article-title": "Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines",
"author": "Liu",
"doi-asserted-by": "crossref",
"first-page": "119",
"journal-title": "J Genet Genomics",
"key": "10.1016/j.virs.2025.07.002_bib50",
"volume": "47",
"year": "2020"
},
{
"DOI": "10.1128/mBio.02335-21",
"article-title": "SARS-CoV-2 Nsp5 demonstrates two distinct mechanisms targeting RIG-I and MAVS to evade the innate immune response",
"author": "Liu",
"doi-asserted-by": "crossref",
"journal-title": "mBio",
"key": "10.1016/j.virs.2025.07.002_bib51",
"volume": "12",
"year": "2021"
},
{
"DOI": "10.1093/jmcb/mjad024",
"article-title": "SARS-CoV-2 main protease Nsp5 cleaves and inactivates human tRNA methyltransferase TRMT1",
"author": "Lu",
"doi-asserted-by": "crossref",
"journal-title": "J. Mol. Cell Biol.",
"key": "10.1016/j.virs.2025.07.002_bib52",
"volume": "15",
"year": "2023"
},
{
"DOI": "10.1021/acsinfecdis.2c00458",
"article-title": "Identification of human host substrates of the SARS-CoV-2 M(pro) and PL(pro) using subtiligase N-terminomics",
"author": "Luo",
"doi-asserted-by": "crossref",
"first-page": "749",
"journal-title": "ACS Infect. Dis.",
"key": "10.1016/j.virs.2025.07.002_bib53",
"volume": "9",
"year": "2023"
},
{
"DOI": "10.1016/j.cell.2008.02.031",
"article-title": "SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs",
"author": "Ma",
"doi-asserted-by": "crossref",
"first-page": "303",
"journal-title": "Cell",
"key": "10.1016/j.virs.2025.07.002_bib54",
"volume": "133",
"year": "2008"
},
{
"DOI": "10.3390/v16060898",
"article-title": "Human coronavirus 229E infection inactivates pyroptosis executioner gasdermin D but ultimately leads to lytic cell death partly mediated by Gasdermin E",
"author": "Martiáñez-Vendrell",
"doi-asserted-by": "crossref",
"first-page": "898",
"journal-title": "Viruses",
"key": "10.1016/j.virs.2025.07.002_bib55",
"volume": "16",
"year": "2024"
},
{
"DOI": "10.1038/s41467-021-25796-w",
"article-title": "Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential",
"author": "Meyer",
"doi-asserted-by": "crossref",
"first-page": "5553",
"journal-title": "Nat. Commun.",
"key": "10.1016/j.virs.2025.07.002_bib56",
"volume": "12",
"year": "2021"
},
{
"DOI": "10.3390/ijms21249523",
"article-title": "Identification of host cellular protein substrates of SARS-COV-2 main protease",
"author": "Miczi",
"doi-asserted-by": "crossref",
"first-page": "9523",
"journal-title": "Int. J. Mol. Sci.",
"key": "10.1016/j.virs.2025.07.002_bib57",
"volume": "21",
"year": "2020"
},
{
"DOI": "10.1146/annurev-cellbio-092910-154005",
"article-title": "The role of Atg proteins in autophagosome formation",
"author": "Mizushima",
"doi-asserted-by": "crossref",
"first-page": "107",
"journal-title": "Annu. Rev. Cell Dev. Biol.",
"key": "10.1016/j.virs.2025.07.002_bib58",
"volume": "27",
"year": "2011"
},
{
"DOI": "10.1080/22221751.2020.1870414",
"article-title": "SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species",
"author": "Moustaqil",
"doi-asserted-by": "crossref",
"first-page": "178",
"journal-title": "Emerg. Microb. Infect.",
"key": "10.1016/j.virs.2025.07.002_bib59",
"volume": "10",
"year": "2021"
},
{
"DOI": "10.1371/journal.ppat.1005942",
"article-title": "Rabies virus infection induces the Formation of stress granules closely connected to the viral factories",
"author": "Nikolic",
"doi-asserted-by": "crossref",
"journal-title": "PLoS Pathog.",
"key": "10.1016/j.virs.2025.07.002_bib60",
"volume": "12",
"year": "2016"
},
{
"DOI": "10.1016/j.celrep.2021.109892",
"article-title": "Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CL(pro) substrate degradome",
"author": "Pablos",
"doi-asserted-by": "crossref",
"first-page": "109892",
"journal-title": "Cell Rep",
"key": "10.1016/j.virs.2025.07.002_bib61",
"volume": "37",
"year": "2021"
},
{
"DOI": "10.3390/cells13191614",
"article-title": "A gain-of-function cleavage of TonEBP by coronavirus NSP5 to suppress IFN-β expression",
"author": "Park",
"doi-asserted-by": "crossref",
"first-page": "1614",
"journal-title": "Cells",
"key": "10.1016/j.virs.2025.07.002_bib62",
"volume": "13",
"year": "2024"
},
{
"DOI": "10.1016/j.molcel.2022.04.033",
"article-title": "Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells",
"author": "Planès",
"doi-asserted-by": "crossref",
"first-page": "2385",
"journal-title": "Mol. Cell",
"key": "10.1016/j.virs.2025.07.002_bib63",
"volume": "82",
"year": "2022"
},
{
"DOI": "10.1038/s41577-020-0288-3",
"article-title": "RIG-I-like receptors: their regulation and roles in RNA sensing",
"author": "Rehwinkel",
"doi-asserted-by": "crossref",
"first-page": "537",
"journal-title": "Nat. Rev. Immunol.",
"key": "10.1016/j.virs.2025.07.002_bib64",
"volume": "20",
"year": "2020"
},
{
"DOI": "10.1016/j.cell.2010.01.040",
"article-title": "The inflammasomes",
"author": "Schroder",
"doi-asserted-by": "crossref",
"first-page": "821",
"journal-title": "Cell",
"key": "10.1016/j.virs.2025.07.002_bib65",
"volume": "140",
"year": "2010"
},
{
"DOI": "10.1128/jvi.01909-23",
"article-title": "SARS-CoV-2 and oncolytic EV-D68-encoded proteases differentially regulate pyroptosis",
"author": "Shen",
"doi-asserted-by": "crossref",
"journal-title": "J. Virol.",
"key": "10.1016/j.virs.2025.07.002_bib66",
"volume": "98",
"year": "2024"
},
{
"DOI": "10.1128/mbio.02739-21",
"article-title": "Coronaviruses Nsp5 antagonizes porcine gasdermin D-mediated pyroptosis by cleaving pore-forming p30 fragment",
"author": "Shi",
"doi-asserted-by": "crossref",
"journal-title": "mBio",
"key": "10.1016/j.virs.2025.07.002_bib67",
"volume": "13",
"year": "2022"
},
{
"DOI": "10.1038/cr.2013.159",
"article-title": "A current perspective of autophagosome biogenesis",
"author": "Shibutani",
"doi-asserted-by": "crossref",
"first-page": "58",
"journal-title": "Cell Res.",
"key": "10.1016/j.virs.2025.07.002_bib68",
"volume": "24",
"year": "2014"
},
{
"DOI": "10.1016/j.jbc.2023.102990",
"article-title": "The main protease of SARS-CoV-2 cleaves histone deacetylases and DCP1A, attenuating the immune defense of the interferon-stimulated genes",
"author": "Song",
"doi-asserted-by": "crossref",
"journal-title": "J. Biol. Chem.",
"key": "10.1016/j.virs.2025.07.002_bib69",
"volume": "299",
"year": "2023"
},
{
"DOI": "10.1016/j.immuni.2012.03.013",
"article-title": "The JAK-STAT pathway at twenty",
"author": "Stark",
"doi-asserted-by": "crossref",
"first-page": "503",
"journal-title": "Immunity",
"key": "10.1016/j.virs.2025.07.002_bib70",
"volume": "36",
"year": "2012"
},
{
"DOI": "10.1111/imr.12884",
"article-title": "The NLRP1 and CARD8 inflammasomes",
"author": "Taabazuing",
"doi-asserted-by": "crossref",
"first-page": "13",
"journal-title": "Immunol. Rev.",
"key": "10.1016/j.virs.2025.07.002_bib71",
"volume": "297",
"year": "2020"
},
{
"DOI": "10.1371/journal.pbio.3002144",
"article-title": "Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome",
"author": "Tsu",
"doi-asserted-by": "crossref",
"journal-title": "PLoS Biol.",
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"DOI": "10.3390/ijms24076371",
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"first-page": "6371",
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{
"DOI": "10.1021/jm980071x",
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"author": "Webber",
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"year": "2005"
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{
"DOI": "10.1371/journal.ppat.1011702",
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"first-page": "221",
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"DOI": "10.1002/med.21783",
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"author": "Xiong",
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"first-page": "1965",
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"year": "2021"
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{
"DOI": "10.1007/s11427-022-2295-0",
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"author": "Xiong",
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"year": "2023"
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{
"DOI": "10.1073/pnas.1835675100",
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"author": "Yang",
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"first-page": "13190",
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"DOI": "10.1038/s41392-023-01386-8",
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"first-page": "109",
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{
"DOI": "10.1038/s41419-019-2178-9",
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"year": "2019"
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{
"DOI": "10.1038/s41392-023-01580-8",
"article-title": "The role of cell death in SARS-CoV-2 infection",
"author": "Yuan",
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"first-page": "357",
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{
"DOI": "10.1073/pnas.2107108118",
"article-title": "Protease cleavage of RNF20 facilitates coronavirus replication via stabilization of SREBP1",
"author": "Zhang",
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"journal-title": "Proc. Natl. Acad. Sci. U. S. A.",
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"volume": "118",
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{
"DOI": "10.1016/j.virs.2025.03.006",
"article-title": "The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D",
"author": "Zhang",
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"first-page": "324",
"journal-title": "Virol. Sin.",
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"year": "2025"
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"DOI": "10.1007/s00018-024-05458-y",
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"author": "Zhang",
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"first-page": "433",
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"volume": "81",
"year": "2024"
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{
"DOI": "10.1186/s43556-022-00083-2",
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"author": "Zhang",
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"DOI": "10.1016/j.ijantimicag.2024.107096",
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"author": "Zheng",
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{
"DOI": "10.1038/s41392-022-00878-3",
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"author": "Zheng",
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"year": "2022"
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{
"DOI": "10.1128/jvi.00253-24",
"article-title": "Deep profiling of potential substrate atlas of porcine epidemic diarrhea virus 3C-like protease",
"author": "Zhou",
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"journal-title": "J. Virol.",
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"volume": "98",
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{
"DOI": "10.1021/acsinfecdis.3c00418",
"article-title": "Ubiquitin ligase Parkin regulates the stability of SARS-CoV-2 main protease and suppresses viral replication",
"author": "Zhou",
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"first-page": "879",
"journal-title": "ACS Infect. Dis.",
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{
"DOI": "10.1002/jmv.29891",
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"author": "Zhou",
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"DOI": "10.1126/sciadv.add7197",
"article-title": "Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system",
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"DOI": "10.1016/j.virol.2016.12.005",
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