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Structural biology of SARS-CoV-2 exoribonuclease/N7–methyltransferase (nsp14), 2′–O–methyltransferase (nsp16) and their enhancing protein (nsp10)

ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 111-127 | Received 27 Aug 2022, Accepted 02 Oct 2023, Published online: 28 Oct 2023

References

  • V’kovski P, Kratzel A, Steiner S, et al. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2021;19:155–170. doi:10.1038/s41579-020-00468-6
  • Perlman S, Netland J. Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol. 2009;7:439–450. doi:10.1038/nrmicro2147
  • Finkel Y, Mizrahi O, Nachshon A, et al. The coding capacity of SARS-CoV-2. Nature. 2021;589:125–130. doi:10.1038/s41586-020-2739-1
  • Thoms M, Buschauer R, Ameismeier M, et al. Structural basis for translational shutdown and immune evasion by the nsp1 protein of SARS-CoV-2. Science. 2020;369:1249–1255. doi:10.1126/science.abc8665
  • Schubert K, Karousis ED, Jomaa A, et al. SARS-CoV-2 nsp1 binds the ribosomal mRNA channel to inhibit translation. Nat Struct Mol Biol. 2020;27:959–966. doi:10.1038/s41594-020-0511-8
  • Sims AC, Ostermann J, Denison MR. Mouse hepatitis virus replicase proteins associate with two distinct populations of intracellular membranes. J Virol. 2000;74:5647–5654. doi:10.1128/JVI.74.12.5647-5654.2000
  • Snijder EJ, Decroly E, Ziebuhr J. The nonstructural proteins directing coronavirus RNA synthesis and processing. Adv Virus Res. 2016;96:59–126. doi:10.1016/bs.aivir.2016.08.008
  • V’kovski P, Gerber M, Kelly J, et al. Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling. eLife. 2019;8:e42037. doi:10.7554/eLife.42037
  • Ghosh S, Dellibovi-Ragheb TA, Kerviel A, et al. β-Coronaviruses use lysosomes for egress instead of the biosynthetic secretory pathway. Cell. 2020;183:1520–1535.e14. doi:10.1016/j.cell.2020.10.039
  • Wang D, Jiang A, Feng J, et al. The SARS-CoV-2 subgenome landscape and its novel regulatory features. Mol Cell. 2021;81:2135–2147.e5. doi:10.1016/j.molcel.2021.02.036
  • Kim D, Lee J-Y, Yang J-S, et al. The architecture of SARS-CoV-2 transcriptome. Cell. 2020;181:914–921.e10. doi:10.1016/j.cell.2020.04.011
  • Tomasello G, Armenia I, Molla G. The Protein Imager: a full-featured online molecular viewer interface with server-side HQ-rendering capabilities. Elofsson A, Editor. Bioinformatics. 2020;36:2909–2911.
  • Wu A, Peng Y, Huang B, et al. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe. 2020;27:325–328. doi:10.1016/j.chom.2020.02.001
  • Gao Y, Yan L, Huang Y, et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science. 2020;368:779–782. doi:10.1126/science.abb7498
  • Kirchdoerfer RN, Ward AB. Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat Commun. 2019;10:2342. doi:10.1038/s41467-019-10280-3
  • Tanner JA, Watt RM, Chai Y-B, et al. The severe acute respiratory syndrome (SARS) coronavirus NTPase/helicase belongs to a distinct class of 5′ to 3′ viral helicases. J Biol Chem. 2003;278:39578–39582. doi:10.1074/jbc.C300328200
  • Jia Z, Yan L, Ren Z, et al. Delicate structural coordination of the Severe Acute Respiratory Syndrome coronavirus nsp13 upon ATP hydrolysis. Nucl Acids Res. 2019;47:6538–6550. doi:10.1093/nar/gkz409
  • Adedeji AO, Marchand B, te Velthuis AJW, et al. Mechanism of nucleic acid unwinding by SARS-CoV helicase. Darlix J-LE, editor. PLoS ONE. 2012;7:e36521. doi:10.1371/journal.pone.0036521
  • Chen J, Malone B, Llewellyn E, et al. Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex. Cell. 2020;182:1560–1573.e13.e13. doi:10.1016/j.cell.2020.07.033
  • Eckerle LD, Lu X, Sperry SM, et al. High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants. J Virol. 2007;81:12135–12144. doi:10.1128/JVI.01296-07
  • Eckerle LD, Becker MM, Halpin RA, et al. Infidelity of SARS-CoV nsp14-exonuclease mutant virus replication Is revealed by complete genome sequencing. Emerman M, editor. PLoS Pathog. 2010;6:e1000896. doi:10.1371/journal.ppat.1000896
  • Minskaia E, Hertzig T, Gorbalenya AE, et al. Discovery of an RNA virus 3’->5’ exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc Natl Acad Sci. 2006;103:5108–5113. doi:10.1073/pnas.0508200103
  • Bouvet M, Debarnot C, Imbert I, et al. In vitro reconstitution of SARS-coronavirus mRNA Cap methylation. Buchmeier MJ, editor. PLoS Pathog. 2010;6:e1000863. doi:10.1371/journal.ppat.1000863
  • Bouvet M, Imbert I, Subissi L, et al. RNA 3’-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex. Proc Natl Acad Sci. 2012;109:9372–9377. doi:10.1073/pnas.1201130109
  • Smith EC, Denison MR. Implications of altered replication fidelity on the evolution and pathogenesis of coronaviruses. Curr Opin Virol. 2012;2:519–524. doi:10.1016/j.coviro.2012.07.005
  • Ma Y, Wu L, Shaw N, et al. Structural basis and functional analysis of the SARS coronavirus nsp14–nsp10 complex. Proc Natl Acad Sci. 2015;112:9436–9441. doi:10.1073/pnas.1508686112
  • Daffis S, Szretter KJ, Schriewer J, et al. 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature. 2010;468:452–456. doi:10.1038/nature09489
  • Ivanov KA, Thiel V, Dobbe JC, et al. Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. J Virol. 2004;78:5619–5632. doi:10.1128/JVI.78.11.5619-5632.2004
  • Slanina H, Madhugiri R, Bylapudi G, et al. Coronavirus replication–transcription complex: Vital and selective NMPylation of a conserved site in nsp9 by the NiRAN-RdRp subunit. Proc Natl Acad Sci. 2021;118:e2022310118. doi:10.1073/pnas.2022310118
  • Yan L, Ge J, Zheng L, et al. Cryo-EM structure of an extended SARS-CoV-2 replication and transcription complex reveals an intermediate state in Cap synthesis. Cell. 2021;184:184–193.e10. doi:10.1016/j.cell.2020.11.016
  • Chen Y, Cai H, Pan J, et al. Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase. Proc Natl Acad Sci. 2009;106:3484–3489. doi:10.1073/pnas.0808790106
  • Chen Y, Su C, Ke M, et al. Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2′-O-methylation by nsp16/nsp10 protein complex. Kuhn RJ, editor. PLoS Pathog. 2011;7:e1002294. doi:10.1371/journal.ppat.1002294
  • Decroly E, Imbert I, Coutard B, et al. Coronavirus nonstructural protein 16 Is a Cap-0 binding enzyme possessing (nucleoside-2′O)-methyltransferase activity. J Virol. 2008;82:8071–8084. doi:10.1128/JVI.00407-08
  • Ferron F, Subissi L, De Morais S, et al. Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA. Proc Natl Acad Sci. 2018;115:E162–E171. doi:10.1073/pnas.1718806115
  • Ivanov KA, Ziebuhr J. Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5J-triphosphatase activities. J Virol. 2004;78:7833–7838. doi:10.1128/JVI.78.14.7833-7838.2004
  • Romano M, Ruggiero A, Squeglia F, et al. A structural view of SARS-CoV-2 RNA replication machinery: RNA synthesis, proofreading and final capping. Cells. 2020;9:1267. doi:10.3390/cells9051267
  • Yan L, Yang Y, Li M, et al. Coupling of N7-methyltransferase and 3′-5′ exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading. Cell. 2021;184:3474–3485.e11. doi:10.1016/j.cell.2021.05.033
  • Krafcikova P, Silhan J, Nencka R, et al. Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin. Nat Commun. 2020;11:3717. doi:10.1038/s41467-020-17495-9
  • Bouvet M, Imbert I, Subissi L, et al. RNA 3’-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex. Proc Natl Acad Sci. 2012;109:9372–9377. doi:10.1073/pnas.1201130109
  • Joseph JS, Saikatendu KS, Subramanian V, et al. Crystal structure of nonstructural protein 10 from the severe acute respiratory syndrome coronavirus reveals a novel fold with Two zinc-binding motifs. J Virol. 2006;80:7894–7901. doi:10.1128/JVI.00467-06
  • Su D, Lou Z, Sun F, et al. Dodecamer structure of severe acute respiratory syndrome coronavirus nonstructural protein nsp10. J Virol. 2006;80:7902–7908. doi:10.1128/JVI.00483-06
  • Chen Y, Su C, Ke M, et al. Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2′-O-methylation by nsp16/nsp10 protein complex. Kuhn RJ, editor. PLoS Pathog. 2011;7:e1002294. doi:10.1371/journal.ppat.1002294
  • Chen Y, Cai H, Pan J, et al. Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase. Proc Natl Acad Sci. 2009;106:3484–3489. doi:10.1073/pnas.0808790106
  • Kozielski F, Sele C, VO T, et al. Identification of fragments binding to SARS-CoV-2 nsp10 reveals ligand-binding sites in conserved interfaces between nsp10 and nsp14/nsp16. RSC Chem Biol. 2022;3:44–55. doi:10.1039/D1CB00135C
  • Rogstam A, Nyblom M, Christensen S, et al. Crystal structure of non-structural protein 10 from severe acute respiratory syndrome coronavirus-2. Int J Mol Sci. 2020;21:7375. doi:10.3390/ijms21197375
  • Ma Y, Wu L, Shaw N, et al. Structural basis and functional analysis of the SARS coronavirus nsp14–nsp10 complex. Proc Natl Acad Sci. 2015;112:9436–9441. doi:10.1073/pnas.1508686112
  • Lin S, Chen H, Chen Z, et al. Crystal structure of SARS-CoV-2 nsp10 bound to nsp14-ExoN domain reveals an exoribonuclease with both structural and functional integrity. Nucl Acids Res. 2021;49:5382–5392. doi:10.1093/nar/gkab320
  • Moeller NH, Shi K, Demir Ö, et al. Structure and dynamics of SARS-CoV-2 proofreading exoribonuclease ExoN. Proc Natl Acad Sci. 2022;119:e2106379119. doi:10.1073/pnas.2106379119
  • Liu C, Shi W, Becker ST, et al. Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme. Science. 2021;373:1142–1146. doi:10.1126/science.abi9310
  • Imprachim N, Yosaatmadja Y, Newman JA. Crystal structures and fragment screening of SARS-CoV-2 nsp14 reveal details of exoribonuclease activation and mRNA capping and provide starting points for antiviral drug development. Nucl Acids Res. 2023;51:475–487. doi:10.1093/nar/gkac1207
  • Czarna A, Plewka J, Kresik L, et al. Refolding of lid subdomain of SARS-CoV-2 nsp14 upon nsp10 interaction releases exonuclease activity. Structure. 2022;30:1050–1054.e2.e2. doi:10.1016/j.str.2022.04.014
  • Kottur J, Rechkoblit O, Quintana-Feliciano R, et al. High-resolution structures of the SARS-CoV-2 N7-methyltransferase inform therapeutic development. Nat Struct Mol Biol. 2022;29:850–853. doi:10.1038/s41594-022-00828-1
  • Decroly E, Debarnot C, Ferron F, et al. Crystal structure and functional analysis of the SARS-coronavirus RNA Cap 2′-O-methyltransferase nsp10/nsp16 complex. Rey FA, editor. PLoS Pathog. 2011;7:e1002059. doi:10.1371/journal.ppat.1002059
  • Minasov G, Rosas-Lemus M, Shuvalova L, et al. Mn2 + coordinates Cap-0-RNA to align substrates for efficient 2′-O-methyl transfer by SARS-CoV-2 nsp16. Sci Signal. 2021;14:689. doi:10.1126/scisignal.abh2071
  • Rosas-Lemus M, Minasov G, Shuvalova L, et al. High-resolution structures of the SARS-CoV-2 2′-O-methyltransferase reveal strategies for structure-based inhibitor design. Sci Signal. 2020;13:eabe1202. doi:10.1126/scisignal.abe1202
  • Viswanathan T, Arya S, Chan S-H, et al. Structural basis of RNA cap modification by SARS-CoV-2. Nat Commun. 2020;11:3718. doi:10.1038/s41467-020-17496-8
  • Lin S, Chen H, Ye F, et al. Crystal structure of SARS-CoV-2 nsp10/nsp16 2′-O-methylase and its implication on antiviral drug design. Signal Transduct Target Ther. 2020;5:131. doi:10.1038/s41392-020-00241-4
  • Wilamowski M, Sherrell DA, Minasov G, et al. 2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography. Proc Natl Acad Sci. 2021;118:e2100170118. doi:10.1073/pnas.2100170118
  • Viswanathan T, Misra A, Chan S-H, et al. A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2′-O methylation of its first nucleotide. Nat Commun. 2021;12:3287. doi:10.1038/s41467-021-23594-y
  • Klima M, Khalili Yazdi A, Li F, et al. Crystal structure of SARS-CoV -2 nsp10–nsp16 in complex with small molecule inhibitors, SS148 and WZ16. Protein Sci. 2022;31. doi:10.1002/pro.4395
  • Ogando NS, Ferron F, Decroly E, et al. The curious case of the nidovirus exoribonuclease: Its role in RNA synthesis and replication fidelity. Front Microbiol. 2019;10:1813. doi:10.3389/fmicb.2019.01813
  • Barnes MH, Spacciapoli P, Li DH, et al. The 3′–5′ exonuclease site of DNA polymerase III from Gram-positive bacteria: definition of a novel motif structure. Gene. 1995;165:45–50. doi:10.1016/0378-1119(95)00530-J
  • Deming DJ, Graham RL, Denison MR, et al. Processing of open Reading frame 1a replicase proteins nsp7 to nsp10 in murine hepatitis virus strain A59 replication. J Virol. 2007;81:10280–10291. doi:10.1128/JVI.00017-07
  • Pearce NM, Krojer T, Bradley AR, et al. A multi-crystal method for extracting obscured crystallographic states from conventionally uninterpretable electron density. Nat Commun. 2017;8:15123. doi:10.1038/ncomms15123
  • Khater S, Kumar P, Dasgupta N, et al. Combining SARS-CoV-2 proofreading exonuclease and RNA-dependent RNA polymerase inhibitors as a strategy to combat COVID-19: a high-throughput in silico screening. Front Microbiol. 2021;12:647693. doi:10.3389/fmicb.2021.647693
  • Shannon A, Le NT-T, Selisko B, et al. Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites. Antiviral Res. 2020;178:104793. doi:10.1016/j.antiviral.2020.104793
  • Narayanan N, Nair DT. Ritonavir may inhibit exoribonuclease activity of nsp14 from the SARS-CoV-2 virus and potentiate the activity of chain terminating drugs. Int J Biol Macromol. 2021;168:272–278. doi:10.1016/j.ijbiomac.2020.12.038

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