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Molecular basis for specific viral RNA recognition and 2'-O-ribose methylation by the dengue virus nonstructural protein 5 (NS5).

Zhao Y, Soh TS, Lim SP, Chung KY, Swaminathan K, Vasudevan SG, Shi PY, Lescar J, Luo D
Proc Natl Acad Sci U S A 112 14834-9 (2015)
Cited: 55 times
EuropePMC logo PMID: 26578813

Abstract

Dengue virus (DENV) causes several hundred million human infections and more than 20,000 deaths annually. Neither an efficacious vaccine conferring immunity against all four circulating serotypes nor specific drugs are currently available to treat this emerging global disease. Capping of the DENV RNA genome is an essential structural modification that protects the RNA from degradation by 5' exoribonucleases, ensures efficient expression of viral proteins, and allows escape from the host innate immune response. The large flavivirus nonstructural protein 5 (NS5) (105 kDa) has RNA methyltransferase activities at its N-terminal region, which is responsible for capping the virus RNA genome. The methyl transfer reactions are thought to occur sequentially using the strictly conserved flavivirus 5' RNA sequence as substrate (GpppAG-RNA), leading to the formation of the 5' RNA cap: G0pppAG-RNA → (m7)G0pppAG-RNA ("cap-0")→(m7)G0pppAm2'-O-G-RNA ("cap-1"). To elucidate how viral RNA is specifically recognized and methylated, we determined the crystal structure of a ternary complex between the full-length NS5 protein from dengue virus, an octameric cap-0 viral RNA substrate bearing the authentic DENV genomic sequence (5'-(m7)G0pppA1G2U3U4G5U6U7-3'), and S-adenosyl-l-homocysteine (SAH), the by-product of the methylation reaction. The structure provides for the first time, to our knowledge, a molecular basis for specific adenosine 2'-O-methylation, rationalizes mutagenesis studies targeting the K61-D146-K180-E216 enzymatic tetrad as well as residues lining the RNA binding groove, and offers previously unidentified mechanistic and evolutionary insights into cap-1 formation by NS5, which underlies innate immunity evasion by flaviviruses.

Reviews - 5dto mentioned but not cited (3)

  1. The Many Faces of the Flavivirus NS5 Protein in Antagonism of Type I Interferon Signaling. Best SM. J Virol 91 e01970-16 (2017)
  2. Structure and function of Zika virus NS5 protein: perspectives for drug design. Wang B, Thurmond S, Hai R, Song J. Cell Mol Life Sci 75 1723-1736 (2018)
  3. Molecular Insights into the Flavivirus Replication Complex. van den Elsen K, Quek JP, Luo D. Viruses 13 956 (2021)

Articles - 5dto mentioned but not cited (19)

  1. Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin. Krafcikova P, Silhan J, Nencka R, Boura E. Nat Commun 11 3717 (2020)
  2. The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication. Sacramento CQ, de Melo GR, de Freitas CS, Rocha N, Hoelz LV, Miranda M, Fintelman-Rodrigues N, Marttorelli A, Ferreira AC, Barbosa-Lima G, Abrantes JL, Vieira YR, Bastos MM, de Mello Volotão E, Nunes EP, Tschoeke DA, Leomil L, Loiola EC, Trindade P, Rehen SK, Bozza FA, Bozza PT, Boechat N, Thompson FL, de Filippis AM, Brüning K, Souza TM. Sci Rep 7 40920 (2017)
  3. Structure and function of the Zika virus full-length NS5 protein. Zhao B, Yi G, Du F, Chuang YC, Vaughan RC, Sankaran B, Kao CC, Li P. Nat Commun 8 14762 (2017)
  4. The crystal structure of Zika virus NS5 reveals conserved drug targets. Duan W, Song H, Wang H, Chai Y, Su C, Qi J, Shi Y, Gao GF. EMBO J 36 919-933 (2017)
  5. Molecular basis for specific viral RNA recognition and 2'-O-ribose methylation by the dengue virus nonstructural protein 5 (NS5). Zhao Y, Soh TS, Lim SP, Chung KY, Swaminathan K, Vasudevan SG, Shi PY, Lescar J, Luo D. Proc Natl Acad Sci U S A 112 14834-14839 (2015)
  6. Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo. de Freitas CS, Higa LM, Sacramento CQ, Ferreira AC, Reis PA, Delvecchio R, Monteiro FL, Barbosa-Lima G, James Westgarth H, Vieira YR, Mattos M, Rocha N, Hoelz LVB, Leme RPP, Bastos MM, Rodrigues GOL, Lopes CEM, Queiroz-Junior CM, Lima CX, Costa VV, Teixeira MM, Bozza FA, Bozza PT, Boechat N, Tanuri A, Souza TML. PLoS Negl Trop Dis 13 e0007072 (2019)
  7. Evaluation of Sofosbuvir (β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine) as an inhibitor of Dengue virus replication. Xu HT, Colby-Germinario SP, Hassounah SA, Fogarty C, Osman N, Palanisamy N, Han Y, Oliveira M, Quan Y, Wainberg MA. Sci Rep 7 6345 (2017)
  8. 2'-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography. Wilamowski M, Sherrell DA, Minasov G, Kim Y, Shuvalova L, Lavens A, Chard R, Maltseva N, Jedrzejczak R, Rosas-Lemus M, Saint N, Foster IT, Michalska K, Satchell KJF, Joachimiak A. Proc Natl Acad Sci U S A 118 e2100170118 (2021)
  9. Structural basis for STAT2 suppression by flavivirus NS5. Wang B, Thurmond S, Zhou K, Sánchez-Aparicio MT, Fang J, Lu J, Gao L, Ren W, Cui Y, Veit EC, Hong H, Evans MJ, O'Leary SE, García-Sastre A, Zhou ZH, Hai R, Song J. Nat Struct Mol Biol 27 875-885 (2020)
  10. Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase. Jain R, Butler KV, Coloma J, Jin J, Aggarwal AK. Sci Rep 7 1632 (2017)
  11. A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2'-O methylation of its first nucleotide. Viswanathan T, Misra A, Chan SH, Qi S, Dai N, Arya S, Martinez-Sobrido L, Gupta YK. Nat Commun 12 3287 (2021)
  12. Looking for inhibitors of the dengue virus NS5 RNA-dependent RNA-polymerase using a molecular docking approach. Galiano V, Garcia-Valtanen P, Micol V, Encinar JA. Drug Des Devel Ther 10 3163-3181 (2016)
  13. Mn2+ coordinates Cap-0-RNA to align substrates for efficient 2'-O-methyl transfer by SARS-CoV-2 nsp16. Minasov G, Rosas-Lemus M, Shuvalova L, Inniss NL, Brunzelle JS, Daczkowski CM, Hoover P, Mesecar AD, Satchell KJF. Sci Signal 14 eabh2071 (2021)
  14. Cross-serotypically conserved epitope recommendations for a universal T cell-based dengue vaccine. Ahmed SF, Quadeer AA, Barton JP, McKay MR. PLoS Negl Trop Dis 14 e0008676 (2020)
  15. The structure of the binary methyltransferase-SAH complex from Zika virus reveals a novel conformation for the mechanism of mRNA capping. Chatrin C, Talapatra SK, Canard B, Kozielski F. Oncotarget 9 3160-3171 (2018)
  16. Crystal Structures of Flavivirus NS5 Guanylyltransferase Reveal a GMP-Arginine Adduct. Jia H, Zhong Y, Peng C, Gong P. J Virol 96 e0041822 (2022)
  17. Structure-first identification of RNA elements that regulate dengue virus genome architecture and replication. Boerneke MA, Gokhale NS, Horner SM, Weeks KM. Proc Natl Acad Sci U S A 120 e2217053120 (2023)
  18. research-article A metal ion orients mRNA to ensure accurate 2'-O ribosyl methylation of the first nucleotide of the SARS-CoV-2 genome. Viswanathan T, Misra A, Chan SH, Qi S, Dai N, Arya S, Martinez-Sobrido L, Gupta YK. bioRxiv 2021.03.12.435174 (2021)
  19. Structural and functional basis of low-affinity SAM/SAH-binding in the conserved MTase of the multi-segmented Alongshan virus distantly related to canonical unsegmented flaviviruses. Chen H, Lin S, Yang F, Chen Z, Guo L, Yang J, Lin X, Wang L, Duan Y, Wen A, Zhang X, Dai Y, Yin K, Yuan X, Yu C, He Y, He B, Cao Y, Dong H, Li J, Zhao Q, Liu Q, Lu G. PLoS Pathog 19 e1011694 (2023)


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  1. Dengue Virus Non-Structural Protein 5. El Sahili A, Lescar J. Viruses 9 E91 (2017)
  2. New developments in flavivirus drug discovery. Kok WM. Expert Opin Drug Discov 11 433-445 (2016)
  3. In vitro methods for testing antiviral drugs. Rumlová M, Ruml T. Biotechnol Adv 36 557-576 (2018)
  4. Zika virus proteins at an atomic scale: how does structural biology help us to understand and develop vaccines and drugs against Zika virus infection? Valente AP, Moraes AH. J Venom Anim Toxins Incl Trop Dis 25 e20190013 (2019)
  5. Universal RNA Secondary Structure Insight Into Mosquito-Borne Flavivirus (MBFV) cis-Acting RNA Biology. Zeng M, Duan Y, Zhang W, Wang M, Jia R, Zhu D, Liu M, Zhao X, Yang Q, Wu Y, Zhang S, Liu Y, Zhang L, Yu Y, Chen S, Cheng A. Front Microbiol 11 473 (2020)
  6. Flavivirus nonstructural proteins and replication complexes as antiviral drug targets. van den Elsen K, Chew BLA, Ho JS, Luo D. Curr Opin Virol 59 101305 (2023)
  7. An epigenetic 'extreme makeover': the methylation of flaviviral RNA (and beyond). Ruggieri A, Helm M, Chatel-Chaix L. RNA Biol 18 696-708 (2021)
  8. The Impact of Epitranscriptomics on Antiviral Innate Immunity. Mersinoglu B, Cristinelli S, Ciuffi A. Viruses 14 1666 (2022)

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  1. Structural basis of RNA cap modification by SARS-CoV-2. Viswanathan T, Arya S, Chan SH, Qi S, Dai N, Misra A, Park JG, Oladunni F, Kovalskyy D, Hromas RA, Martinez-Sobrido L, Gupta YK. Nat Commun 11 3718 (2020)
  2. High-resolution structures of the SARS-CoV-2 2'-O-methyltransferase reveal strategies for structure-based inhibitor design. Rosas-Lemus M, Minasov G, Shuvalova L, Inniss NL, Kiryukhina O, Brunzelle J, Satchell KJF. Sci Signal 13 eabe1202 (2020)
  3. Potent Allosteric Dengue Virus NS5 Polymerase Inhibitors: Mechanism of Action and Resistance Profiling. Lim SP, Noble CG, Seh CC, Soh TS, El Sahili A, Chan GK, Lescar J, Arora R, Benson T, Nilar S, Manjunatha U, Wan KF, Dong H, Xie X, Shi PY, Yokokawa F. PLoS Pathog 12 e1005737 (2016)
  4. Zika Virus Methyltransferase: Structure and Functions for Drug Design Perspectives. Coutard B, Barral K, Lichière J, Selisko B, Martin B, Aouadi W, Lombardia MO, Debart F, Vasseur JJ, Guillemot JC, Canard B, Decroly E. J Virol 91 e02202-16 (2017)
  5. Structures of NS5 Methyltransferase from Zika Virus. Coloma J, Jain R, Rajashankar KR, García-Sastre A, Aggarwal AK. Cell Rep 16 3097-3102 (2016)
  6. A general method for rapid and cost-efficient large-scale production of 5' capped RNA. Fuchs AL, Neu A, Sprangers R. RNA 22 1454-1466 (2016)
  7. NS3 helicase from dengue virus specifically recognizes viral RNA sequence to ensure optimal replication. Swarbrick CMD, Basavannacharya C, Chan KWK, Chan SA, Singh D, Wei N, Phoo WW, Luo D, Lescar J, Vasudevan SG. Nucleic Acids Res 45 12904-12920 (2017)
  8. Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragment-based drug design. Benmansour F, Trist I, Coutard B, Decroly E, Querat G, Brancale A, Barral K. Eur J Med Chem 125 865-880 (2017)
  9. NS5 from Dengue Virus Serotype 2 Can Adopt a Conformation Analogous to That of Its Zika Virus and Japanese Encephalitis Virus Homologues. El Sahili A, Soh TS, Schiltz J, Gharbi-Ayachi A, Seh CC, Shi PY, Lim SP, Lescar J. J Virol 94 e01294-19 (2019)
  10. Discovery of Bispecific Lead Compounds from Azadirachta indica against ZIKA NS2B-NS3 Protease and NS5 RNA Dependent RNA Polymerase Using Molecular Simulations. Kumar S, El-Kafrawy SA, Bharadwaj S, Maitra SS, Alandijany TA, Faizo AA, Khateb AM, Dwivedi VD, Azhar EI. Molecules 27 2562 (2022)
  11. Biochemical and Biophysical Characterisation of the Hepatitis E Virus Guanine-7-Methyltransferase. Hooda P, Ishtikhar M, Saraswat S, Bhatia P, Mishra D, Trivedi A, Kulandaisamy R, Aggarwal S, Munde M, Ali N, AlAsmari AF, Rauf MA, Inampudi KK, Sehgal D. Molecules 27 1505 (2022)
  12. Methyltransferase-Deficient Avian Flaviviruses Are Attenuated Due to Suppression of Viral RNA Translation and Induction of a Higher Innate Immunity. Wu X, Zhang Y, Wang M, Chen S, Liu M, Zhu D, Zhao X, Wu Y, Yang Q, Zhang S, Huang J, Ou X, Zhang L, Liu Y, Yu Y, Gao Q, Mao S, Sun D, Tian B, Yin Z, Jing B, Cheng A, Jia R. Front Immunol 12 751688 (2021)
  13. Analysis of methyltransferase (MTase) domain from Zika virus (ZIKV). Afaq S, Atiya A, Malik A, Alwabli AS, Alzahrani DA, Al-Solami HM, Alzahrani O, Alam Q, Kamal MA, Abulfaraj AA, Alhebshi AM, Tarique M. Bioinformation 16 229-235 (2020)
  14. In Silico Analysis of Dengue Virus Serotype 2 Mutations Detected at the Intrahost Level in Patients with Different Clinical Outcomes. Torres MC, Martins Karl AL, Müller Pereira da Silva M, Dardenne LE, Bispo de Filippis AM. Microbiol Spectr 9 e0025621 (2021)
  15. A conserved arginine in NS5 binds genomic 3' stem-loop RNA for primer-independent initiation of flavivirus RNA replication. Wang S, Chan KWK, Tan MJA, Flory C, Luo D, Lescar J, Forwood JK, Vasudevan SG. RNA 28 177-193 (2022)
  16. The RNA polymerase of cytoplasmically replicating Zika virus binds with chromatin DNA in nuclei and regulates host gene transcription. Li P, Wu J, Liu S, Lu R, Jiang H, Wang N, Luo M, Guo L, Xiao J, Bu L, Liu L, Xing F, Peng H, Li C, Ma L, Zhao B, Zhou Z, Guo D. Proc Natl Acad Sci U S A 119 e2205013119 (2022)
  17. Virtual Screening of Drug-Like Compounds as Potential Inhibitors of the Dengue Virus NS5 Protein. García-Ariza LL, Rocha-Roa C, Padilla-Sanabria L, Castaño-Osorio JC. Front Chem 10 637266 (2022)
  18. CMTr mediated 2'-O-ribose methylation status of cap-adjacent nucleotides across animals. Dix TC, Haussmann IU, Brivio S, Nallasivan MP, HadzHiev Y, Müller F, Müller B, Pettitt J, Soller M. RNA 28 1377-1390 (2022)
  19. The substitution at residue 218 of the NS5 protein methyltransferase domain of Tembusu virus impairs viral replication and translation and may triggers RIG-I-like receptor signaling. Wu X, Pan Y, Huang J, Huang S, Wang M, Chen S, Liu M, Zhu D, Zhao X, Wu Y, Yang Q, Zhang S, Ou X, Zhang L, Liu Y, Yu Y, Gao Q, Mao S, Sun D, Tian B, Yin Z, Jing B, Cheng A, Jia R. Poult Sci 101 102017 (2022)
  20. In silico and in vitro studies of potential inhibitors against Dengue viral protein NS5 Methyl Transferase from Ginseng and Notoginseng. Jarerattanachat V, Boonarkart C, Hannongbua S, Auewarakul P, Ardkhean R. J Tradit Complement Med 13 1-10 (2023)
  21. A novel live attenuated duck Tembusu virus vaccine targeting N7 methyltransferase protects ducklings against pathogenic strains. Wu X, Huang S, Wang M, Chen S, Liu M, Zhu D, Zhao X, Wu Y, Yang Q, Zhang S, Huang J, Ou X, Zhang L, Liu Y, Yu Y, Gao Q, Mao S, Sun D, Tian B, Yin Z, Jing B, Cheng A, Jia R. Vet Res 54 47 (2023)
  22. Application of MCMC-Based Bayesian Modeling for Genetic Evolutionary and Dynamic Change Analysis of Zika Virus. Shao T, Pan J, Zhang S, Xin Z, Wang G. Front Genet 10 1319 (2019)
  23. Broad-Spectrum Small-Molecule Inhibitors Targeting the SAM-Binding Site of Flavivirus NS5 Methyltransferase. Samrat SK, Bashir Q, Huang Y, Trieshmann CW, Tharappel AM, Zhang R, Chen K, Zheng YG, Li Z, Li H. ACS Infect Dis 9 1319-1333 (2023)
  24. New oxindole carboxamides as inhibitors of DENV NS5 RdRp: Design, synthesis, docking and Biochemical characterization. Koraboina CP, Akshinthala P, Katari NK, Adarasandi R, Jonnalagadda SB, Gundla R. Heliyon 9 e21510 (2023)
  25. Phylodynamics of dengue virus 2 in Nicaragua leading up to the 2019 epidemic reveals a role for lineage turnover. Thongsripong P, Edgerton SV, Bos S, Saborío S, Kuan G, Balmaseda A, Harris E, Bennett SN. BMC Ecol Evol 23 58 (2023)


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