1,521
Views
6
CrossRef citations to date
0
Altmetric
Review

Analysis of the SARS-CoV-2-host protein interaction network reveals new biology and drug candidates: focus on the spike surface glycoprotein and RNA polymerase

, , &
Pages 881-895 | Received 14 Dec 2020, Accepted 24 Mar 2021, Published online: 06 Apr 2021

References

  • Gates B. Responding to Covid-19 — a once-in-a-century pandemic? N Engl J Med. 2020;382(18):1677–1679.
  • Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020 Apr 16;181(2):271–280 e8.
  • Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020 Jul;583(7816):459–468.
  • Dunham WH, Mullin M, Gingras AC. Affinity-purification coupled to mass spectrometry: basic principles and strategies. Proteomics. 2012 May;12(10):1576–1590.
  • Cloutier P, Poitras C, Faubert D, et al. Upstream ORF-encoded ASDURF is a novel prefoldin-like subunit of the PAQosome. J Proteome Res. 2020 Jan 3;19(1):18–27.
  • Guzzi PH, Mercatelli D, Ceraolo C, et al. Master regulator analysis of the SARS-CoV-2/Human interactome. J Clin Med. 2020 Apr 1;9(4):4.
  • Khorsand B, Savadi A, Naghibzadeh M. SARS-CoV-2-human protein-protein interaction network. Inf Med Unlocked. 2020;20:100413.
  • Hussain I, Pervaiz N, Khan A, et al. Evolutionary and structural analysis of SARS-CoV-2 specific evasion of host immunity. Genes Immun. 2020 [2020 dec 01];21(6–8):409–419.
  • Daniloski Z, Jordan TX, Wessels HH, et al. Identification of required host factors for SARS-CoV-2 infection in human cells. Cell. 2020 Oct;184(1):24.
  • Wei J, Alfajaro MM, DeWeirdt PC, et al. Genome-wide CRISPR screens reveal host factors critical for SARS-CoV-2 infection. Cell. 2021;184(1):76–91.e13.
  • Sun J, He W-T, Wang L, et al. COVID-19: epidemiology, evolution, and cross-disciplinary perspectives. Trends Mol Med. 2020 ;26(5):483–495.
  • Gui M, Song W, Zhou H, et al. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res. 2017 [2017 Jan 01];27(1):119–129.
  • Qing E, Gallagher T. SARS coronavirus redux.Trends Immunol. 2020 [2020 Apr 01];41(4):271–273.
  • Wrapp D, Wang N, Corbett KS, et al., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 367(6483): 1260. 2020.
  • Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215–220. 2020 May 01.
  • Wang Q, Zhang Y, Wu L, et al. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell. 2020 [2020 May 14];181(4):894–904.e9.
  • Ortega JT, Serrano ML, Pujol FH, et al. Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: an in silico analysis. Excli J. 2020 Mar 18;19:410-417.
  • Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Nat Acad Sci. 2020;117(21):11727.
  • Bilinska K, Jakubowska P, Von Bartheld CS, et al. Expression of the SARS-CoV-2 entry proteins, ACE2 and TMPRSS2, in cells of the olfactory epithelium: identification of cell types and trends with age. ACS Chem Neurosci. 2020 [2020 Jun 03];11(11):1555–1562.
  • Datta PK, Liu F, Fischer T, et al. SARS-CoV-2 pandemic and research gaps: understanding SARS-CoV-2 interaction with the ACE2 receptor and implications for therapy. Theranostics. 2020;10(16):7448–7464.
  • Walls AC, Park YJ, Tortorici MA, et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020 Apr 16;181(2):281–292 e6.
  • Vankadari N. Structure of furin protease binding to SARS-CoV-2 spike glycoprotein and implications for potential targets and virulence. J Phys Chem Lett. 2020;11(16):6655–6663.
  • Rossi GA, Sacco O, Mancino E, et al. Differences and similarities between SARS-CoV and SARS-CoV-2: spike receptor-binding domain recognition and host cell infection with support of cellular serine proteases. Infection. 2020 [2020 Oct 01];48(5):665–669.
  • Luan J, Lu Y, Jin X, et al. Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection. Biochem Biophys Res Commun. 2020 [2020 May 21];526(1):165–169.
  • Baig MS, Alagumuthu M, Rajpoot S, et al. Identification of a potential peptide inhibitor of SARS-CoV-2 targeting its entry into the host cells. Drugs R D. 2020 [2020 Sep 01];20(3):161–169.
  • Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020;367(6485):1444.
  • Chen L, Li X, Chen M, et al. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020;116(6):1097–1100.
  • Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020;323(18):1843–1844.
  • Luo Y, Liu C, Guan T, et al. Association of ACE2 genetic polymorphisms with hypertension-related target organ damages in south Xinjiang. Hypertens Res. 2019 [2019 May 01];42(5):681–689.
  • Meng N, Zhang Y, Ma J, et al. Association of polymorphisms of angiotensin I converting enzyme 2 with retinopathy in type 2 diabetes mellitus among Chinese individuals. Eye. 2015 [2015 Feb 01];29(2):266–271.
  • Hussain M, Jabeen N, Raza F, et al. Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein. J Med Virol. 2020 [2020 Sep 01];92(9):1580–1586.
  • Othman H, Bouslama Z, Brandenburg J-T, et al. Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism. Biochem Biophys Res Commun. 2020 [2020 Jun 30];527(3):702–708.
  • Benetti E, Tita R, Spiga O, et al. ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population. Eur J Hum Genet. 2020 [2020 Nov 01];28(11):1602–1614.
  • Sorokina M, Teixeira J MC, Barrera-Vilarmau S, et al. Structural models of human ACE2 variants with SARS-CoV-2 Spike protein for structure-based drug design. Sci Data. 2020 [2020 Jul 16];7(1):309.
  • Hashizume M, Gonzalez G, Ono C, et al. Population-specific ACE2 single-nucleotide polymorphisms have limited impact on SARS-CoV-2 infectivity in vitro. Viruses. 2021;13(1):67.
  • Zhang L, Jackson CB, Mou H, et al. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat Commun. 2020 [2020 Nov 26];11(1):6013.
  • Liu Z, VanBlargan LA, Bloyet L-M, et al. Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. Cell Host Microbe. 2021 [2021 Jan 27];29(3):477–488.e4.
  • Li Q, Wu J, Nie J, et al. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell. 2020;182(5):1284–1294.e9.
  • Galloway S, Paul P, Paul D, et al. Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States. MMWR Morb Mortal Wkly Rep. 2021;12(70):95–99. December 29, 2020–January.
  • Villoutreix BO, Calvez V, Marcelin A-G, et al. In silico investigation of the new UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 variants with a focus at the ACE2–spike RBD interface. Int J Mol Sci. 2021;22(4):1695.
  • Simonovich VA, Burgos Pratx LD, Scibona P, et al. A randomized trial of convalescent plasma in covid-19 severe pneumonia. N Engl J Med. 2021 Feb 18;384(7):619-629.
  • Jiang S, Hillyer C, Du L. Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends Immunol. 2020 May;41(5):355–359.
  • Whisenant J, Burgess K. Blocking coronavirus 19 Infection via the SARS-CoV-2 spike protein: initial Steps.ACS Med Chem Lett. 2020 [2020 Jun 11];11(6):1076–1078.
  • Yi C, Sun X, Ye J, et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol. 2020 [2020 Jun 01];17(6):621–630.
  • Tian X, Li C, Huang A, et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect. 2020 [2020 Jan 01];9(1):382–385.
  • Brielle ES, Schneidman-Duhovny D, Linial M. The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. Viruses. 2020;12(5):5.
  • Seydoux E, Homad LJ, MacCamy AJ, et al. Analysis of a SARS-CoV-2-infected individual reveals development of potent neutralizing antibodies with limited somatic mutation. Immunity. 2020 [2020 Jul 14];53(1):98–105.e5.
  • Cao Y, Su B, Guo X, et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell. 2020;182(1):73–84.e16. 2020 Jul 09.
  • Wu Y, Wang F, Shen C, et al. A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Science. 2020;368(6496):1274.
  • Ju B, Zhang Q, Ge J, et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature. 2020 [2020 Aug 01];584(7819):115–119.
  • Brouwer PJM, Caniels TG, Van Der Straten K, et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science. 2020;369(6504):643.
  • Wang C, Li W, Drabek D, et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun. 2020 [2020 May 04];11(1):2251.
  • Wrapp D, De Vlieger D, Corbett KS, et al. Structural basis for potent neutralization of betacoronaviruses by single-domain camelid antibodies. Cell. 2020 [2020 May 28];181(5):1004–1015.e15.
  • Song Y, Song J, Wei X, et al. Discovery of aptamers targeting the receptor-binding domain of the SARS-CoV-2 spike glycoprotein. Anal Chem. 2020 [2020 Jun 21];92(14):9895–9900.
  • Coronavirus (COVID-19) Update: FDA authorizes monoclonal antibodies for treatment of COVID-19 [Internet]. U.S. food and drug administration; 2020 Nov 19. [cited 2020 Dec 1]. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid–19
  • Coronavirus (COVID-19) Update: November 9, 2020 [Internet]. U.S. food and drug administration; 2020 Nov 9. [cited 2020 Dec 1]. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-november–9–2020
  • Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell. 2020 May 14;181(4):905–913 e7.
  • Lei C, Qian K, Li T, et al. Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig. Nat Commun. 2020 [2020 Apr 24];11(1):2070.
  • Han Y, Král P. Computational design of ACE2-based peptide inhibitors of SARS-CoV-2.ACS Nano. 2020 Apr 28;14(4):5143-5147.
  • Huang X, Pearce R, Zhang Y. De novo design of protein peptides to block association of the SARS-CoV-2 spike protein with human ACE2. Aging (Albany NY). 2020;12(12):11263–11276.
  • Xia S, Zhu Y, Liu M, et al. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell Mol Immunol. 2020 [2020 Jul 01];17(7):765–767.
  • Xia S, Liu M, Wang C, et al. Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. 2020 [2020 Apr 01];30(4):343–355.
  • Zhu Y, Yu D, Yan H, et al. Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity. J Virol. 2020;94(14):e00635–20.
  • Robson B. COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance. Comput Biol Med. 2020;121:103749. 2020 Jun 01.
  • Di Paola L, Hadi-Alijanvand H, Song X, et al. The discovery of a putative allosteric site in the SARS-CoV-2 spike protein using an integrated structural/dynamic approach. J Proteome Res. 2020 [2020 Jun 17];19(11):4576–4586.
  • Honarmand Ebrahimi K. SARS-CoV-2 spike glycoprotein-binding proteins expressed by upper respiratory tract bacteria may prevent severe viral infection. FEBS Lett. 2020;594(11):1651–1660.
  • Tai W, He L, Zhang X, et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol. 2020 [2020 Jun 01];17(6):613–620.
  • Wang C, Wang S, Li D, et al. Human intestinal defensin 5 inhibits SARS-CoV-2 invasion by cloaking ACE2. Gastroenterology. 2020 Sep;159(3):1145–1147.e4.
  • Feng S, Luan X, Wang Y, et al. Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein. Infect Genet Evol. 2020;85:104419.
  • Straughn AR, Kakar SS. Withaferin A: a potential therapeutic agent against COVID-19 infection. J Ovarian Res. 2020;13(1):79.
  • 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(19):10280–10291.
  • Ogando NS, Zevenhoven-Dobbe JC, Van Der Meer Y, et al., The enzymatic activity of the nsp14 exoribonuclease is critical for replication of MERS-CoV and SARS-CoV-2. J Virol. 94(23): e01246–20. 2020. .
  • Wang Y, Sun Y, Wu A, et al. Coronavirus nsp10/nsp16 methyltransferase can be targeted by nsp10-derived peptide in vitro and in vivo to reduce replication and pathogenesis. J Virol. 2015;89(16):8416–8427.
  • Lehmann KC, Snijder EJ, Posthuma CC, et al. What we know but do not understand about nidovirus helicases. Virus Res. 2015;202:12–32.
  • Giri R, Bhardwaj T, Shegane M, et al. Understanding COVID-19 via comparative analysis of dark proteomes of SARS-CoV-2, human SARS and bat SARS-like coronaviruses. Cell Mol Life Sci. 2020;25:1–34.
  • 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 May 20;9(5):1267.
  • Santerre M, Arjona SP, Allen CN, et al. Why do SARS-CoV-2 NSPs rush to the ER? J Neurol. 2020 Sep 1;1-10.
  • Kumar P, Bhardwaj T, Kumar A, et al. Reprofiling of approved drugs against SARS-CoV-2 main protease: an in-silico study. J Biomol Struct Dyn. 2020 Nov 12:1-15.
  • Khan MT, Ali A, Wang Q, et al. Marine natural compounds as potents inhibitors against the main protease of SARS-CoV-2—a molecular dynamic study. J Biomol Struct Dyn. 2020 Jun 1:1-11.
  • Cong Y, Ulasli M, Schepers H, et al. Nucleocapsid protein recruitment to replication-transcription complexes plays a crucial role in coronaviral life cycle. J Virol. 2020;94(4):e01925–19.
  • Khan A, Tahir Khan M, Saleem S, et al. Structural insights into the mechanism of RNA recognition by the N-terminal RNA-binding domain of the SARS-CoV-2 nucleocapsid phosphoprotein. Comput Struct Biotechnol J. 2020 [2020 Jan 01];18:2174–2184.
  • Chen Y, Su C, Ke M, et al. Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2ʹ-O-methylation by nsp16/nsp10 protein complex. PLoS Pathog. 2011;7(10):e1002294–e1002294.
  • Encinar JA, Menendez JA. Potential drugs targeting early innate immune evasion of SARS-coronavirus 2 via 2ʹ-O-methylation of viral RNA. Viruses. 2020;12(5):525.
  • Gao Y, Yan L. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science. 2020 May 15;368(6492):779-782.
  • Lehmann KC, Gulyaeva A, Zevenhoven-Dobbe JC, et al. Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses. Nucleic Acids Res. 2015 Sep 30;43(17):8416–8434.
  • 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. 2020;S0092-8674(20):31533–31536.
  • Wang Q, Wu J, Wang H, et al. Structural basis for RNA replication by the SARS-CoV-2 polymerase. Cell. 2020 Jul 23;182(2):417–428.e13.
  • Peng Q, Peng R, Yuan B, et al. Structural and biochemical characterization of the nsp12-nsp7-nsp8 core polymerase complex from SARS-CoV-2. Cell Rep. 2020 Jun 16;31(11):107774.
  • Hillen HS, Kokic G, Farnung L, et al. Structure of replicating SARS-CoV-2 polymerase. Nature. 2020 [2020 Aug 01];584(7819):154–156.
  • Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci. 2020 May 1;248:117477.
  • Iftikhar H, Ali HN, Farooq S, et al. Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach. Comput Biol Med. 2020 Jul;122:103848.
  • Zhang W-F, Stephen P, J-f T, et al. Novel coronavirus polymerase and nucleotidyl-transferase structures: potential to target new outbreaks. J Phys Chem Lett. 2020;11(11):4430–4435.
  • Wu C, Liu Y, Yang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B. 2020 May;10(5):766–788.
  • Mirza MU, Froeyen M. Structural elucidation of SARS-CoV-2 vital proteins: computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase. J Pharm Anal. 2020 Aug;10(4):320–328.
  • Khan A, Khan M, Saleem S, et al. Phylogenetic analysis and structural perspectives of rna-dependent rna-polymerase inhibition from SARs-CoV-2 with natural products. Interdiscip Sci. 2020;12(3):335–348.
  • Gordon CJ, Tchesnokov EP, Woolner E, et al. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem. 2020;295(20):6785–6797. .
  • Konkolova E, Klima M, Nencka R, et al. Structural analysis of the putative SARS-CoV-2 primase complex. J Struct Biol. 2020 Aug 1;211(2):107548.
  • Chen J, Malone B, Llewellyn E, et al. Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex. Cell. 2020 Sep 17;182(6):1560–1573.e13.
  • Krichel B, Falke S, Hilgenfeld R, et al. Processing of the SARS-CoV pp1a/ab nsp7-10 region. Biochem J. 2020 Mar 13;477(5):1009–1019.
  • Subissi L, Posthuma CC, Collet A, et al. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):E3900–9.
  • Mutlu O, Ugurel OM, Sariyer E, et al. Targeting SARS-CoV-2 Nsp12/Nsp8 interaction interface with approved and investigational drugs: an in silico structure-based approach. J Biomol Struct Dynamics. 2020; 1–13. DOI: 10.1080/07391102.2020.1819882.
  • Chand GB, Banerjee A, Azad GK. Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure. PeerJ. 2020;8:e9492–e9492.
  • Pachetti M, Marini B, Benedetti F, et al. Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. J Transl Med. 2020 Apr 22;18(1):179.
  • Tchesnokov EP, Gordon CJ, Woolner E, et al. Template-dependent inhibition of coronavirus RNA-dependent RNA polymerase by remdesivir reveals a second mechanism of action. J Biol Chem. 2020 Nov 20;295(47):16156–16165.
  • Littler DR, Gully BS, Colson RN, et al. Crystal structure of the SARS-CoV-2 non-structural Protein 9. Nsp9iScience. 2020 Jul 24;23(7):101258.
  • Miknis ZJ, Donaldson EF, Umland TC, et al. Severe acute respiratory syndrome coronavirus nsp9 dimerization is essential for efficient viral growth. J Virol. 2009 Apr;83(7):3007–3018.
  • Egloff MP, Ferron F, Campanacci V, et al. The severe acute respiratory syndrome-coronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world. Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3792–3796.
  • Shu T, Huang M, Wu D, et al. SARS-coronavirus-2 Nsp13 possesses NTPase and RNA helicase activities that can be inhibited by bismuth salts. Virol Sin. 2020;35(3):321–329.
  • Jia Z, Yan L, Ren Z, et al. Delicate structural coordination of the severe acute respiratory syndrome coronavirus Nsp13 upon ATP hydrolysis. Nucleic Acids Res. 2019 Jul 9;47(12):6538–6550.
  • Cui S, Hao W. Deducing the crystal structure of MERS-CoV helicase. Methods Mol Biol. 2020;2099:69–85.
  • White MA, Lin W, Cheng X. Discovery of COVID-19 Inhibitors Targeting the SARS-CoV-2 Nsp13 helicase. J Phys Chem Lett. 2020;11(21):9144–9151.
  • Gurung AB. In silico structure modelling of SARS-CoV-2 Nsp13 helicase and Nsp14 and repurposing of FDA approved antiviral drugs as dual inhibitors. Gene Rep. 2020;21:100860.
  • Ugurel OM, Mutlu O, Sariyer E, et al. Evaluation of the potency of FDA-approved drugs on wild type and mutant SARS-CoV-2 helicase (Nsp13). Int J Biol Macromol. 2020 Nov 15;163:1687–1696.
  • 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(19):7375.
  • 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(1):3717.
  • Viswanathan T, Arya S, Chan S-H, et al. Structural basis of RNA cap modification by SARS-CoV-2. Nat Commun. 2020;11(1):3718.
  • Mahalapbutr P, Kongtaworn N, Rungrotmongkol T. Structural insight into the recognition of S-adenosyl-L-homocysteine and sinefungin in SARS-CoV-2 Nsp16/Nsp10 RNA cap 2ʹ-O-methyltransferase. Comput Struct Biotechnol J. 2020;18:2757–2765.
  • Sharma K, Morla S, Goyal A, et al. Computational guided drug repurposing for targeting 2ʹ-O-ribose methyltransferase of SARS-CoV-2. Life Sci. 2020;259:118169.
  • Eckerle LD, Becker MM, Halpin RA, et al. Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing. PLoS Pathog. 2010;6(5):e1000896–e1000896.
  • Robson F, Khan KS, Le TK, et al. Coronavirus RNA Proofreading: molecular Basis and Therapeutic Targeting. Mol Cell. 2020;79(5):710–727.
  • Bouvet M, Lugari A, Posthuma CC, et al. Coronavirus Nsp10, a critical co-factor for activation of multiple replicative enzymes. J Biol Chem. 2014;289(37):25783–25796.
  • Ferron F, Subissi L, Silveira De Morais AT, et al. Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA. Proc Natl Acad Sci U S A. 2018;115(2):E162–E171.
  • Ahmed-Belkacem R, Sutto-Ortiz P, Guiraud M, et al. Synthesis of adenine dinucleosides SAM analogs as specific inhibitors of SARS-CoV nsp14 RNA cap guanine-N7-methyltransferase. Eur J Med Chem. 2020;201:112557.
  • Shannon A, Le N-T-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.
  • Gentile D, Fuochi V, Rescifina A, et al. New anti SARS-Cov-2 targets for quinoline derivatives chloroquine and hydroxychloroquine. Int J Mol Sci. 2020;21(16):5856.
  • Azad GK. Identification of novel mutations in the methyltransferase complex (Nsp10-Nsp16) of SARS-CoV-2. Biochem Biophys Rep. 2020;24:100833.
  • Lamontagne F, Agoritsas T, Macdonald H, et al. A living WHO guideline on drugs for covid-19. BMJ (Clin Res Ed). 2020 Sep 4;370:m3379.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.