An alphacoronavirus polymerase structure reveals conserved replication factor functions
Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biol...
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| Published in | Nucleic acids research Vol. 52; no. 10; pp. 5975 - 5986 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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England
Oxford University Press
10.06.2024
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| Abstract | Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine structures of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. One structure shows an unexpected nsp8 stoichiometry despite remaining bound to RNA. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for in vitro RNA synthesis for alpha- and betacoronaviruses. Our work demonstrates the importance of studying diverse coronaviruses in revealing aspects of coronavirus replication and identifying areas of conservation to be targeted by antiviral drugs.
Graphical Abstract
Graphical Abstract |
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| AbstractList | Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine structures of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. One structure shows an unexpected nsp8 stoichiometry despite remaining bound to RNA. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for
in vitro
RNA synthesis for alpha- and betacoronaviruses. Our work demonstrates the importance of studying diverse coronaviruses in revealing aspects of coronavirus replication and identifying areas of conservation to be targeted by antiviral drugs.
Graphical Abstract Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine structures of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. One structure shows an unexpected nsp8 stoichiometry despite remaining bound to RNA. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for in vitro RNA synthesis for alpha- and betacoronaviruses. Our work demonstrates the importance of studying diverse coronaviruses in revealing aspects of coronavirus replication and identifying areas of conservation to be targeted by antiviral drugs.Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine structures of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. One structure shows an unexpected nsp8 stoichiometry despite remaining bound to RNA. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for in vitro RNA synthesis for alpha- and betacoronaviruses. Our work demonstrates the importance of studying diverse coronaviruses in revealing aspects of coronavirus replication and identifying areas of conservation to be targeted by antiviral drugs. Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine structures of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. One structure shows an unexpected nsp8 stoichiometry despite remaining bound to RNA. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for in vitro RNA synthesis for alpha- and betacoronaviruses. Our work demonstrates the importance of studying diverse coronaviruses in revealing aspects of coronavirus replication and identifying areas of conservation to be targeted by antiviral drugs. Graphical Abstract Graphical Abstract Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine structures of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. One structure shows an unexpected nsp8 stoichiometry despite remaining bound to RNA. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for in vitro RNA synthesis for alpha- and betacoronaviruses. Our work demonstrates the importance of studying diverse coronaviruses in revealing aspects of coronavirus replication and identifying areas of conservation to be targeted by antiviral drugs. |
| Author | Lee, Kenneth W Coon, Joshua J Kirchdoerfer, Robert N Hoferle, Peter J Chojnacki, Kennan J Anderson, Thomas K |
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| CitedBy_id | crossref_primary_10_1016_j_jbc_2024_107802 crossref_primary_10_3390_cimb46030165 |
| Cites_doi | 10.1007/978-1-4939-2438-7_1 10.1016/j.jsb.2021.107702 10.1016/j.jcv.2020.104391 10.1093/nar/gkp904 10.1073/pnas.2102516118 10.1038/nmeth.4169 10.3201/eid1801.111259 10.1038/s41467-019-10280-3 10.1128/JVI.06635-11 10.1093/nar/gkg916 10.1038/nmeth.2089 10.1016/j.jbc.2022.101923 10.1016/j.bbrc.2022.07.087 10.1107/S2059798318006551 10.1074/jbc.RA120.013679 10.1016/j.jsb.2005.07.007 10.1016/bs.aivir.2016.08.008 10.3390/v13112228 10.1093/cid/ciab456 10.1073/pnas.1323705111 10.1074/jbc.AC120.013056 10.1126/science.abc1560 10.1038/s41467-020-20542-0 10.1016/j.cell.2020.07.033 10.1038/s41467-020-19770-1 10.1038/s41586-020-2012-7 10.7554/eLife.70968 10.1177/1040638713501675 10.1002/pro.3943 10.1107/S0907444910007493 10.1128/jvi.00671-22 10.1038/s41586-020-2008-3 10.1016/j.cell.2020.11.016 10.1016/S0022-2836(03)00865-9 10.1016/j.molcel.2021.01.035 10.3390/ijms23073953 10.3390/v14112434 10.1056/NEJMoa1211721 10.1128/JVI.01244-13 10.1126/sciadv.abf1004 10.1007/s11259-021-09808-0 10.1038/s41467-022-28113-1 10.1038/s41586-020-2368-8 10.1016/j.compbiomed.2022.105455 10.1128/mBio.00221-18 10.1107/S2059798318002425 10.1093/nar/gkab370 |
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| References | Sun (2024060923573174700_B14) 2012; 18 Zaki (2024060923573174700_B3) 2012; 367 Xu (2024060923573174700_B16) 2003; 31 Mastronarde (2024060923573174700_B34) 2005; 152 Xiu (2024060923573174700_B8) 2020; 128 Ma (2024060923573174700_B31) 2022; 145 Chen (2024060923573174700_B27) 2020; 182 Snijder (2024060923573174700_B2) 2003; 331 Shannon (2024060923573174700_B41) 2022; 13 Vlasova (2024060923573174700_B9) 2022; 74 Subissi (2024060923573174700_B21) 2014; 111 Silva (2024060923573174700_B7) 2014; 2014 Emsley (2024060923573174700_B37) 2010; 66 te Velthuis (2024060923573174700_B17) 2010; 38 Fehr (2024060923573174700_B1) 2015; 1282 Pettersen (2024060923573174700_B40) 2021; 30 Yan (2024060923573174700_B10) 2022; 23 Seifert (2024060923573174700_B22) 2021; 10 Pourfarjam (2024060923573174700_B45) 2022; 625 Hillen (2024060923573174700_B23) 2020; 584 Zhou (2024060923573174700_B6) 2020; 579 Krichel (2024060923573174700_B30) 2021; 7 Croll (2024060923573174700_B39) 2018; 74 Punjani (2024060923573174700_B36) 2021; 213 Gordon (2024060923573174700_B43) 2020; 295 Schneider (2024060923573174700_B33) 2012; 9 Snijder (2024060923573174700_B18) 2016; 96 Yan (2024060923573174700_B20) 2020; 184 Agostini (2024060923573174700_B42) 2018; 9 Gordon (2024060923573174700_B44) 2020; 295 Afonine (2024060923573174700_B38) 2018; 74 Kirchdoerfer (2024060923573174700_B19) 2019; 10 Bravo (2024060923573174700_B25) 2021; 81 Kokic (2024060923573174700_B46) 2021; 12 Stevenson (2024060923573174700_B13) 2013; 25 Brian (2024060923573174700_B15) 2005; 287 Krentz (2024060923573174700_B47) 2021; 13 Biswal (2024060923573174700_B49) 2021; 49 Liu (2024060923573174700_B11) 2021; 45 Wu (2024060923573174700_B5) 2020; 579 Xiao (2024060923573174700_B29) 2012; 86 Zhang (2024060923573174700_B12) 2022; 14 Grellet (2024060923573174700_B48) 2022; 298 de Groot (2024060923573174700_B4) 2013; 87 Malone (2024060923573174700_B28) 2021; 118 Campagnola (2024060923573174700_B32) 2022; 96 Yin (2024060923573174700_B24) 2020; 368 Yan (2024060923573174700_B26) 2020; 11 Punjani (2024060923573174700_B35) 2017; 14 36993498 - bioRxiv. 2023 Mar 16:2023.03.15.532841. doi: 10.1101/2023.03.15.532841. |
| References_xml | – volume: 1282 start-page: 1 year: 2015 ident: 2024060923573174700_B1 article-title: Coronaviruses: an overview of their replication and pathogenesis publication-title: Methods Mol. Biol. doi: 10.1007/978-1-4939-2438-7_1 – volume: 213 start-page: 107702 year: 2021 ident: 2024060923573174700_B36 article-title: 3D variability analysis: resolving continuous flexibility and discrete heterogeneity from single particle cryo-EM publication-title: J. Struct. Biol. doi: 10.1016/j.jsb.2021.107702 – volume: 128 start-page: 104391 year: 2020 ident: 2024060923573174700_B8 article-title: A RT-PCR assay for the detection of coronaviruses from four genera publication-title: J. Clin. Virol. doi: 10.1016/j.jcv.2020.104391 – volume: 38 start-page: 203 year: 2010 ident: 2024060923573174700_B17 article-title: The RNA polymerase activity of SARS-coronavirus nsp12 is primer dependent publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkp904 – volume: 118 start-page: e2102516118 year: 2021 ident: 2024060923573174700_B28 article-title: Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex publication-title: Proc. Natl. Acad. Sci. U.S.A. doi: 10.1073/pnas.2102516118 – volume: 14 start-page: 290 year: 2017 ident: 2024060923573174700_B35 article-title: cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination publication-title: Nat. Methods doi: 10.1038/nmeth.4169 – volume: 18 start-page: 161 year: 2012 ident: 2024060923573174700_B14 article-title: Outbreak of porcine epidemic diarrhea in suckling piglets, China publication-title: Emerg. Infect. Dis. doi: 10.3201/eid1801.111259 – volume: 10 start-page: 2342 year: 2019 ident: 2024060923573174700_B19 article-title: Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors publication-title: Nat. Commun. doi: 10.1038/s41467-019-10280-3 – volume: 86 start-page: 4444 year: 2012 ident: 2024060923573174700_B29 article-title: Nonstructural proteins 7 and 8 of feline coronavirus form a 2:1 heterotrimer that exhibits primer-independent RNA polymerase activity publication-title: J. Virol. doi: 10.1128/JVI.06635-11 – volume: 31 start-page: 7117 year: 2003 ident: 2024060923573174700_B16 article-title: Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkg916 – volume: 9 start-page: 671 year: 2012 ident: 2024060923573174700_B33 article-title: NIH image to ImageJ: 25 years of image analysis publication-title: Nat. Methods doi: 10.1038/nmeth.2089 – volume: 298 start-page: 101923 year: 2022 ident: 2024060923573174700_B48 article-title: Replication of the coronavirus genome: a paradox among positive-strand RNA viruses publication-title: J. Biol. Chem. doi: 10.1016/j.jbc.2022.101923 – volume: 625 start-page: 53 year: 2022 ident: 2024060923573174700_B45 article-title: ATP enhances the error-prone ribonucleotide incorporation by the SARS-CoV-2 RNA polymerase publication-title: Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2022.07.087 – volume: 74 start-page: 531 year: 2018 ident: 2024060923573174700_B38 article-title: Real-space refinement in PHENIX for cryo-EM and crystallography publication-title: Acta Crystallogr D Struct Biol doi: 10.1107/S2059798318006551 – volume: 295 start-page: 6785 year: 2020 ident: 2024060923573174700_B43 article-title: Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency publication-title: J. Biol. Chem. doi: 10.1074/jbc.RA120.013679 – volume: 152 start-page: 36 year: 2005 ident: 2024060923573174700_B34 article-title: Automated electron microscope tomography using robust prediction of specimen movements publication-title: J. Struct. Biol. doi: 10.1016/j.jsb.2005.07.007 – volume: 2014 start-page: 004 year: 2014 ident: 2024060923573174700_B7 article-title: Human Respiratory coronaviruses detected In patients with influenza-like illness in Arkansas, USA publication-title: Virol. Mycol. – volume: 96 start-page: 59 year: 2016 ident: 2024060923573174700_B18 article-title: The nonstructural proteins directing coronavirus RNA synthesis and processing publication-title: Adv. Virus Res. doi: 10.1016/bs.aivir.2016.08.008 – volume: 13 start-page: 2228 year: 2021 ident: 2024060923573174700_B47 article-title: Curing cats with feline infectious peritonitis with an oral multi-component drug containing GS-441524 publication-title: Viruses doi: 10.3390/v13112228 – volume: 74 start-page: 446 year: 2022 ident: 2024060923573174700_B9 article-title: Novel canine coronavirus isolated from a hospitalized patient with pneumonia in East Malaysia publication-title: Clin. Infect. Dis. doi: 10.1093/cid/ciab456 – volume: 111 start-page: E3900 year: 2014 ident: 2024060923573174700_B21 article-title: One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities publication-title: Proc. Natl. Acad. Sci. U.S.A. doi: 10.1073/pnas.1323705111 – volume: 295 start-page: 4773 year: 2020 ident: 2024060923573174700_B44 article-title: The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus publication-title: J. Biol. Chem. doi: 10.1074/jbc.AC120.013056 – volume: 368 start-page: 1499 year: 2020 ident: 2024060923573174700_B24 article-title: Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir publication-title: Science doi: 10.1126/science.abc1560 – volume: 12 start-page: 279 year: 2021 ident: 2024060923573174700_B46 article-title: Mechanism of SARS-CoV-2 polymerase stalling by remdesivir publication-title: Nat. Commun. doi: 10.1038/s41467-020-20542-0 – volume: 182 start-page: 1560 year: 2020 ident: 2024060923573174700_B27 article-title: Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex publication-title: Cell doi: 10.1016/j.cell.2020.07.033 – volume: 11 start-page: 5874 year: 2020 ident: 2024060923573174700_B26 article-title: Architecture of a SARS-CoV-2 mini replication and transcription complex publication-title: Nat. Commun. doi: 10.1038/s41467-020-19770-1 – volume: 579 start-page: 270 year: 2020 ident: 2024060923573174700_B6 article-title: A pneumonia outbreak associated with a new coronavirus of probable bat origin publication-title: Nature doi: 10.1038/s41586-020-2012-7 – volume: 10 start-page: e70968 year: 2021 ident: 2024060923573174700_B22 article-title: Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective publication-title: eLife doi: 10.7554/eLife.70968 – volume: 25 start-page: 649 year: 2013 ident: 2024060923573174700_B13 article-title: Emergence of porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences publication-title: J. Vet. Diagn. Invest. doi: 10.1177/1040638713501675 – volume: 287 start-page: 1 year: 2005 ident: 2024060923573174700_B15 article-title: Coronavirus genome structure and replication publication-title: Curr. Top. Microbiol. Immunol. – volume: 30 start-page: 70 year: 2021 ident: 2024060923573174700_B40 article-title: UCSF ChimeraX: structure visualization for researchers, educators, and developers publication-title: Protein Sci. doi: 10.1002/pro.3943 – volume: 66 start-page: 486 year: 2010 ident: 2024060923573174700_B37 article-title: Features and development of Coot publication-title: Acta. Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444910007493 – volume: 96 start-page: e0067122 year: 2022 ident: 2024060923573174700_B32 article-title: The SARS-CoV nsp12 polymerase active site is tuned for large-genome replication publication-title: J. Virol. doi: 10.1128/jvi.00671-22 – volume: 579 start-page: 265 year: 2020 ident: 2024060923573174700_B5 article-title: A new coronavirus associated with human respiratory disease in China publication-title: Nature doi: 10.1038/s41586-020-2008-3 – volume: 184 start-page: 184 year: 2020 ident: 2024060923573174700_B20 article-title: Cryo-EM structure of an extended SARS-CoV-2 replication and transcription complex reveals an intermediate State in cap synthesis publication-title: Cell doi: 10.1016/j.cell.2020.11.016 – volume: 331 start-page: 991 year: 2003 ident: 2024060923573174700_B2 article-title: Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage publication-title: J. Mol. Biol. doi: 10.1016/S0022-2836(03)00865-9 – volume: 81 start-page: 1548 year: 2021 ident: 2024060923573174700_B25 article-title: Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication publication-title: Mol. Cell doi: 10.1016/j.molcel.2021.01.035 – volume: 23 start-page: 3953 year: 2022 ident: 2024060923573174700_B10 article-title: Swine Enteric Coronavirus: diverse pathogen-host interactions publication-title: Int. J. Mol. Sci. doi: 10.3390/ijms23073953 – volume: 14 start-page: 2434 year: 2022 ident: 2024060923573174700_B12 article-title: Porcine Epidemic Diarrhea Virus: an updated overview of virus epidemiology, virulence variation patterns and virus-host interactions publication-title: Viruses doi: 10.3390/v14112434 – volume: 367 start-page: 1814 year: 2012 ident: 2024060923573174700_B3 article-title: Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1211721 – volume: 87 start-page: 7790 year: 2013 ident: 2024060923573174700_B4 article-title: Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group publication-title: J. Virol. doi: 10.1128/JVI.01244-13 – volume: 7 start-page: eabf1004 year: 2021 ident: 2024060923573174700_B30 article-title: Hallmarks of alpha- and betacoronavirus non-structural protein 7+8 complexes publication-title: Sci. Adv. doi: 10.1126/sciadv.abf1004 – volume: 45 start-page: 75 year: 2021 ident: 2024060923573174700_B11 article-title: Porcine enteric coronaviruses: an updated overview of the pathogenesis, prevalence, and diagnosis publication-title: Vet. Res. Commun. doi: 10.1007/s11259-021-09808-0 – volume: 13 start-page: 621 year: 2022 ident: 2024060923573174700_B41 article-title: A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase publication-title: Nat. Commun. doi: 10.1038/s41467-022-28113-1 – volume: 584 start-page: 154 year: 2020 ident: 2024060923573174700_B23 article-title: Structure of replicating SARS-CoV-2 polymerase publication-title: Nature doi: 10.1038/s41586-020-2368-8 – volume: 145 start-page: 105455 year: 2022 ident: 2024060923573174700_B31 article-title: Conserved protein targets for developing pan-coronavirus drugs based on sequence and 3D structure similarity analyses publication-title: Comput. Biol. Med. doi: 10.1016/j.compbiomed.2022.105455 – volume: 9 start-page: e00221-18 year: 2018 ident: 2024060923573174700_B42 article-title: Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease publication-title: mBio doi: 10.1128/mBio.00221-18 – volume: 74 start-page: 519 year: 2018 ident: 2024060923573174700_B39 article-title: ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps publication-title: Acta Crystallogr. D Struct. Biol. doi: 10.1107/S2059798318002425 – volume: 49 start-page: 5956 year: 2021 ident: 2024060923573174700_B49 article-title: Two conserved oligomer interfaces of NSP7 and NSP8 underpin the dynamic assembly of SARS-CoV-2 RdRP publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkab370 – reference: 36993498 - bioRxiv. 2023 Mar 16:2023.03.15.532841. doi: 10.1101/2023.03.15.532841. |
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| SubjectTerms | Animals Coronavirus RNA-Dependent RNA Polymerase - chemistry Coronavirus RNA-Dependent RNA Polymerase - genetics Coronavirus RNA-Dependent RNA Polymerase - metabolism Cryoelectron Microscopy Models, Molecular Porcine epidemic diarrhea virus - enzymology Porcine epidemic diarrhea virus - genetics Protein Structure, Tertiary RNA and RNA-protein complexes RNA, Viral - chemistry RNA, Viral - genetics RNA, Viral - metabolism SARS-CoV-2 - enzymology SARS-CoV-2 - genetics Virus Replication - genetics |
| Title | An alphacoronavirus polymerase structure reveals conserved replication factor functions |
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