The multiple roles of viral 3D^pol protein in picornavirus infections

References

• Solomon T, Lewthwaite P, Perera D, et al. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis. 2010;10(11):778–18. doi: 10.1016/S1473-3099(10)70194-8
   PubMed Web of Science ®Google Scholar
• Zell R, Delwart E, Gorbalenya AE, et al. ICTV virus taxonomy profile: Picornaviridae. J Gen Virol. 2017;98(10):2421–2422. doi: 10.1099/jgv.0.000911
   PubMed Web of Science ®Google Scholar
• Zhu P, Ji W, Li D, et al. Current status of hand-foot-and-mouth disease. J Biomed Sci. 2023;30(1):15. doi: 10.1186/s12929-023-00908-4
   PubMed Web of Science ®Google Scholar
• Zhou J, Li Y, Yin Q, et al. Coxsackievirus A6 pneumonia in a child. Lancet Infect Dis. 2023;23(12):e567. doi: 10.1016/S1473-3099(23)00576-5
   PubMed Web of Science ®Google Scholar
• Dai J, Xu D, Yang C, et al. Severe pneumonia and pathogenic damage in human airway epithelium caused by coxsackievirus B4. Emerg Microbes Infect. 2023;12(2):2261560. doi: 10.1080/22221751.2023.2261560
   PubMed Web of Science ®Google Scholar
• Zhang X-S, Ong JJ, Macgregor L, et al. Transmission dynamics of the 2016-18 outbreak of hepatitis a among men who have sex with men in England and cost-effectiveness analysis of vaccination strategies to prevent future outbreaks. Lancet Reg Health Eur. 2022;19:100426. doi: 10.1016/j.lanepe.2022.100426
   PubMedGoogle Scholar
• Carrillo-Santisteve P, Tavoschi L, Severi E, et al. Seroprevalence and susceptibility to hepatitis a in the European Union and European Economic Area: a systematic review. Lancet Infect Dis. 2017;17(10):e306–e319. doi: 10.1016/S1473-3099(17)30392-4
   PubMed Web of Science ®Google Scholar
• Tambyah PA, Oon J, Asli R, et al. An inactivated enterovirus 71 vaccine is safe and immunogenic in healthy adults: a phase I, double blind, randomized, placebo-controlled, study of two dosages. Vaccine. 2019;37(31):4344–4353. doi: 10.1016/j.vaccine.2019.06.023
   PubMed Web of Science ®Google Scholar
• di Nardo A, Ferretti L, Wadsworth J, et al. Evolutionary and ecological drivers shape the emergence and extinction of foot-and-mouth disease virus lineages. Mol Biol Evol. 2021;38(10):4346–4361. doi: 10.1093/molbev/msab172
   PubMed Web of Science ®Google Scholar
• Maggioli Mayara F, Lawson S, de Lima M, et al. Adaptive immune responses following Senecavirus a infection in pigs. J Virol. 2018;92(3):e01717. doi: 10.1128/JVI.01717-17
   PubMed Web of Science ®Google Scholar
• Chen J, Chu Z, Zhang M, et al. Molecular characterization of a novel clade echovirus 3 isolated from patients with hand-foot-and-mouth disease in southwest China. J Med Virol. 2023;95(11):e29202. doi: 10.1002/jmv.29202
   PubMed Web of Science ®Google Scholar
• Peng T, Yang F, Yang F, et al. Structural diversity and biological role of the 5’ untranslated regions of picornavirus. RNA Biol. 2023;20(1):548–562. doi: 10.1080/15476286.2023.2240992
   PubMed Web of Science ®Google Scholar
• Ferrer-Orta C, Ferrero DS, Verdaguer N, et al. Dual role of the foot-and-mouth disease virus 3B1 protein in the replication complex: as protein primer and as an essential component to recruit 3Dpol to membranes. PLoS Path. 2023;19(5):e1011373. doi: 10.1371/journal.ppat.1011373
   PubMed Web of Science ®Google Scholar
• Abdullah Sahibzada W, Je W, Wang X, et al. Advances and breakthroughs in IRES-directed translation and replication of picornaviruses. MBio. 2023;14(2):e00358–23. doi: 10.1128/mbio.00358-23
   PubMed Web of Science ®Google Scholar
• Zhou L, Lu X, Zhao C, et al. Characterization of a novel picornavirus prevalent in experimental rabbits (Oryctolagus cuniculus). Heliyon. 2023;9(5):e15702. doi: 10.1016/j.heliyon.2023.e15702
   PubMed Web of Science ®Google Scholar
• Linden LV, Wolthers KC, van Kuppeveld FJM. Replication and inhibitors of enteroviruses and parechoviruses. Viruses. 2015;7(8):4529–4562. doi: 10.3390/v7082832
   PubMed Web of Science ®Google Scholar
• Jackson T, Belsham GJ. Picornaviruses: a view from 3A. Viruses. 2021;13(3):456. doi: 10.3390/v13030456
   PubMed Web of Science ®Google Scholar
• Paul Aniko V, Rieder E, Kim Dong W, et al. Identification of an RNA hairpin in poliovirus RNA that serves as the primary template in the in vitro uridylylation of VPg. J Virol. 2000;74(22):10359–10370. doi: 10.1128/JVI.74.22.10359-10370.2000
   PubMed Web of Science ®Google Scholar
• Yang Y, Rijnbrand R, McKnight Kevin L, et al. Sequence requirements for viral RNA replication and VPg uridylylation directed by the internal cis-acting replication element (cre) of human rhinovirus type 14. J Virol. 2002;76(15):7485–7494. doi: 10.1128/JVI.76.15.7485-7494.2002
   PubMed Web of Science ®Google Scholar
• Campagnola G, Weygandt M, Scoggin K, et al. Crystal structure of coxsackievirus B3 3Dpol highlights the functional importance of residue 5 in picornavirus polymerases. J Virol. 2008;82(19):9458–9464. doi: 10.1128/JVI.00647-08
   PubMed Web of Science ®Google Scholar
• Love RA, Maegley KA, Yu X, et al. The crystal structure of the RNA-dependent RNA polymerase from human rhinovirus: A dual function target for common cold antiviral therapy. Structure. 2004;12(8):1533–1544. doi: 10.1016/j.str.2004.05.024
   PubMed Web of Science ®Google Scholar
• Thompson AA, Peersen OB. Structural basis for proteolysis-dependent activation of the poliovirus RNA-dependent RNA polymerase. EMBO J. 2004;23(17):3462–3471. doi: 10.1038/sj.emboj.7600357
   PubMed Web of Science ®Google Scholar
• Ferrer-Orta C, Arias A, Perez-Luque R, et al. Structure of foot-and-mouth disease virus RNA-dependent RNA polymerase and its complex with a template-primer RNA. J Biol Chem. 2004;279(45):47212–47221. doi: 10.1074/jbc.M405465200
   PubMed Web of Science ®Google Scholar
• Gong P, Peersen OB. Structural basis for active site closure by the poliovirus RNA-dependent RNA polymerase. Proc Natl Acad Sci USA. 2010;107(52):22505–22510. doi: 10.1073/pnas.1007626107
   PubMed Web of Science ®Google Scholar
• Watkins CL, Kempf BJ, Beaucourt S, et al. Picornaviral polymerase domain exchanges reveal a modular basis for distinct biochemical activities of viral RNA-dependent RNA polymerases. J Biol Chem. 2020;295(31):10624–10637. doi: 10.1074/jbc.RA120.013906
   PubMed Web of Science ®Google Scholar
• Paul AV, Yin J, Mugavero J, et al. A “slide-back” mechanism for the initiation of protein-primed RNA synthesis by the RNA polymerase of poliovirus. J Biol Chem. 2003;278(45):43951–43960. doi: 10.1074/jbc.M307441200
   PubMed Web of Science ®Google Scholar
• Paul AV, van Boom JH, Filippov D, et al. Protein-primed RNA synthesis by purified poliovirus RNA polymerase. Nature. 1998;393(6682):280–284. doi: 10.1038/30529
   PubMed Web of Science ®Google Scholar
• Paul Aniko V, Peters J, Mugavero J, et al. Biochemical and genetic studies of the VPg uridylylation reaction catalyzed by the RNA polymerase of poliovirus. J Virol. 2003;77(2):891–904. doi: 10.1128/JVI.77.2.891-904.2003
   PubMed Web of Science ®Google Scholar
• Sheng Z, Zhu J, Deng Y-N, et al. Sumoylation modification-mediated cell death. Open Biol. 2021;11(7):210050. doi: 10.1098/rsob.210050
   PubMed Web of Science ®Google Scholar
• Zhu X, Qiu C, Wang Y, et al. FGFR1 SUMOylation coordinates endothelial angiogenic signaling in angiogenesis. Proc Natl Acad Sci U S A. 2022;119(26):e2202631119. doi: 10.1073/pnas.2202631119
   PubMed Web of Science ®Google Scholar
• Buschmann T, Fuchs SY, Lee C-G, et al. Sumo-1 modification of mdm2 prevents its self-ubiquitination and increases mdm2 ability to ubiquitinate p53. Cell. 2000;101(7):753–762. doi: 10.1016/S0092-8674(00)80887-9
   PubMed Web of Science ®Google Scholar
• Bernier-Villamor V, Sampson DA, Matunis MJ, et al. Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell. 2002;108(3):345–356. doi: 10.1016/S0092-8674(02)00630-X
   PubMed Web of Science ®Google Scholar
• Liu Y, Zheng Z, Shu B, et al. SUMO modification stabilizes enterovirus 71 polymerase 3D to facilitate viral replication. J Virol. 2016;90(23):10472–10485. doi: 10.1128/JVI.01756-16
   PubMed Web of Science ®Google Scholar
• Hao H, Hao S, Chen H, et al. N6-methyladenosine modification and METTL3 modulate enterovirus 71 replication. Nucleic Acids Res. 2019;47(1):362–374. doi: 10.1093/nar/gky1007
   PubMed Web of Science ®Google Scholar
• Imai S-I, Armstrong CM, Kaeberlein M, et al. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403(6771):795–800. doi: 10.1038/35001622
   PubMed Web of Science ®Google Scholar
• Jia X, Liu H, Ren X, et al. Nucleolar protein NOC4L inhibits tumorigenesis and progression by attenuating SIRT1-mediated p53 deacetylation. Oncogene. 2022;41(39):4474–4484. doi: 10.1038/s41388-022-02447-y
   PubMed Web of Science ®Google Scholar
• Wang W, Li Y, Zhang Y, et al. SIRT1 mediates the inhibitory effect of Dapagliflozin on EndMT by inhibiting the acetylation of endothelium Notch1. Cardiovasc Diabetol. 2023;22(1):331. doi: 10.1186/s12933-023-02040-x
   PubMed Web of Science ®Google Scholar
• Han Y, Wang L, Cui J, et al. SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5‘UTR RNA. J Cell Sci. 2016;129(24):4534–4547. doi: 10.1242/jcs.193698
   PubMed Web of Science ®Google Scholar
• Liu Y-C, Kuo R-L, Lin J-Y, et al. Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering the nucleus and interfering with Prp8. PLoS Path. 2014;10(6):e1004199. doi: 10.1371/journal.ppat.1004199
   PubMed Web of Science ®Google Scholar
• Lee K-M, Wu C-C, Wu S-E, et al. The RNA-dependent RNA polymerase of enterovirus A71 associates with ribosomal proteins and positively regulates protein translation. RNA Biol. 2020;17(4):608–622. doi: 10.1080/15476286.2020.1722448
   PubMed Web of Science ®Google Scholar
• van der Schaar HM, Dorobantu CM, Albulescu L, et al. Fat(al) attraction: picornaviruses usurp lipid transfer at membrane contact sites to create replication organelles. Trends Microbiol. 2016;24(7):535–546. doi: 10.1016/j.tim.2016.02.017
   PubMed Web of Science ®Google Scholar
• Belov GA, van Kuppeveld FJM. (+)RNA viruses rewire cellular pathways to build replication organelles. Curr Opin Virol. 2012;2(6):740–747. doi: 10.1016/j.coviro.2012.09.006
   PubMed Web of Science ®Google Scholar
• Xiao X, Lei X, Zhang Z, et al. Enterovirus 3A facilitates viral replication by promoting phosphatidylinositol 4-kinase IIIβ-ACBD3 interaction. J Virol. 2017;91(19):e00791–17. doi: 10.1128/JVI.00791-17
   PubMed Web of Science ®Google Scholar
• Greninger Alexander L, Knudsen Giselle M, Betegon M, et al. The 3A protein from multiple picornaviruses utilizes the golgi adaptor protein ACBD3 to recruit PI4KIIIβ. J Virol. 2012;86(7):3605–3616. doi: 10.1128/JVI.06778-11
   PubMed Web of Science ®Google Scholar
• Hsu N-Y, Ilnytska O, Belov G, et al. Viral reorganization of the secretory pathway generates distinct organelles for RNA replication. Cell. 2010;141(5):799–811. doi: 10.1016/j.cell.2010.03.050
   PubMed Web of Science ®Google Scholar
• Zhang Q, Li S, Lei P, et al. ANXA2 facilitates enterovirus 71 infection by interacting with 3D polymerase and PI4KB to assist the assembly of replication organelles. Virol Sin. 2021;36(6):1387–1399. doi: 10.1007/s12250-021-00417-4
   PubMed Web of Science ®Google Scholar
• Mu Z, Wang L, Deng W, et al. Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal membrane. Cell Discov. 2017;3(1):17049. doi: 10.1038/celldisc.2017.49
   PubMedGoogle Scholar
• Su M-Y, Morris KL, Kim DJ, et al. Hybrid structure of the RagA/C-Ragulator mTORC1 activation complex. Mol Cell. 2017;68(5):835–846.e3. doi: 10.1016/j.molcel.2017.10.016
   PubMed Web of Science ®Google Scholar
• Wang X, Hu Z, Zhang W, et al. Inhibition of lysosome-tethered ragulator-rag-3D complex restricts the replication of enterovirus 71 and coxsackie A16. J Cell Bio. 2023;222(12):e202303108. doi: 10.1083/jcb.202303108
   PubMed Web of Science ®Google Scholar
• Huang P-N, Jheng J-R, Arnold JJ, et al. UGGT1 enhances enterovirus 71 pathogenicity by promoting viral RNA synthesis and viral replication. PLoS Path. 2017;13(5):e1006375. doi: 10.1371/journal.ppat.1006375
   PubMed Web of Science ®Google Scholar
• Ning Z, Zhong X, Wu Y, et al. β-asarone improves cognitive impairment and alleviates autophagy in mice with vascular dementia via the cAMP/PKA/CREB pathway. Phytomedicine. 2023;123:155215. doi: 10.1016/j.phymed.2023.155215
   PubMed Web of Science ®Google Scholar
• Xu J, Kong L, Oliver BA, et al. Constitutively active autophagy in macrophages dampens inflammation through metabolic and post-transcriptional regulation of cytokine production. Cell Rep. 2023;42(7):112708. doi: 10.1016/j.celrep.2023.112708
   PubMed Web of Science ®Google Scholar
• Xiang Q, Wan P, Yang G, et al. Beclin1 binds to enterovirus 71 3D protein to promote the virus replication. Viruses. 2020;12(7):756. doi: 10.3390/v12070756
   PubMed Web of Science ®Google Scholar
• Fu Y, Xu W, Chen D, et al. Enterovirus 71 induces autophagy by regulating has-miR-30a expression to promote viral replication. Antiviral Res. 2015;124:43–53. doi: 10.1016/j.antiviral.2015.09.016
   PubMed Web of Science ®Google Scholar
• Abernathy E, Mateo R, Majzoub K, et al. Differential and convergent utilization of autophagy components by positive-strand RNA viruses. PLoS Biol. 2019;17(1):e2006926. doi: 10.1371/journal.pbio.2006926
   PubMed Web of Science ®Google Scholar
• Zhong Y, Wang QJ, Li X, et al. Distinct regulation of autophagic activity by Atg14L and Rubicon associated with beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol. 2009;11(4):468–476. doi: 10.1038/ncb1854
   PubMed Web of Science ®Google Scholar
• Chen X, Wang K, Xing Y, et al. Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity. Protein Cell. 2014;5(12):912–927. doi: 10.1007/s13238-014-0104-6
   PubMed Web of Science ®Google Scholar
• Jo DS, Park NY, Cho D-H. Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases. Exp Mol Med. 2020;52(9):1486–1495. doi: 10.1038/s12276-020-00503-9
   PubMed Web of Science ®Google Scholar
• Liu J, Lu W, Shi B, et al. Peroxisomal regulation of redox homeostasis and adipocyte metabolism. Redox Biol. 2019;24:101167. doi: 10.1016/j.redox.2019.101167
   PubMed Web of Science ®Google Scholar
• You L, Chen J, Liu W, et al. Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation. Virulence. 2020;11(1):537–553. doi: 10.1080/21505594.2020.1766790
   PubMed Web of Science ®Google Scholar
• Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol. 2009;27(1):229–265. doi: 10.1146/annurev.immunol.021908.132715
   PubMedGoogle Scholar
• Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124(4):783–801. doi: 10.1016/j.cell.2006.02.015
   PubMed Web of Science ®Google Scholar
• García-Sastre A. Ten Strategies of interferon evasion by viruses. Cell Host Microbe. 2017;22(2):176–184. doi: 10.1016/j.chom.2017.07.012
   PubMed Web of Science ®Google Scholar
• Wang W, Xiao F, Wan P, et al. EV71 3D protein binds with NLRP3 and enhances the assembly of inflammasome complex. PLoS Path. 2017;13(1):e1006123. doi: 10.1371/journal.ppat.1006123
   PubMed Web of Science ®Google Scholar
• Liu G, Lee J-H, Parker ZM, et al. ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol. 2021;6(4):467–478. doi: 10.1038/s41564-021-00884-1
   PubMed Web of Science ®Google Scholar
• Kato H, Takeuchi O, Sato S, et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006;441(7089):101–105. doi: 10.1038/nature04734
   PubMed Web of Science ®Google Scholar
• Kuo R-L, Chen C-J, Wang Robert YL, et al. Role of enteroviral RNA-dependent RNA polymerase in regulation of MDA5-mediated beta interferon activation. J Virol. 2019;93(10):e00132–19. doi: 10.1128/JVI.00132-19
   PubMed Web of Science ®Google Scholar
• Yang Z, Zheng H, Li H, et al. The expression of IFN-β is suppressed by the viral 3D polymerase via its impact on PGAM5 expression during enterovirus D68 infection. Virus Res. 2021;304:198549. doi: 10.1016/j.virusres.2021.198549
   PubMed Web of Science ®Google Scholar
• Tan C, Qin X, Tan Y, et al. SHFL inhibits enterovirus A71 infection by triggering degradation of viral 3Dpol protein via the ubiquitin–proteasome pathway. J Med Virol. 2023;95(8):e29030. doi: 10.1002/jmv.29030
   PubMed Web of Science ®Google Scholar
• Li L, Bai J, Fan H, et al. E2 ubiquitin-conjugating enzyme UBE2L6 promotes senecavirus a proliferation by stabilizing the viral RNA polymerase. PLoS Path. 2020;16(10):e1008970. doi: 10.1371/journal.ppat.1008970
   PubMed Web of Science ®Google Scholar
• Lawrence P, Schafer EA, Rieder E. The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells. Virology. 2012;425(1):40–52. doi: 10.1016/j.virol.2011.12.019
   PubMed Web of Science ®Google Scholar
• Marsh K, Soros V, Cochrane A. Selective translational repression of HIV-1 RNA by Sam68DeltaC occurs by altering PABP1 binding to unspliced viral RNA. Retrovirology. 2008;5(1):97. doi: 10.1186/1742-4690-5-97
   PubMedGoogle Scholar
• McBride AE, Schlegel A, Kirkegaard K. Human protein Sam68 relocalization and interaction with poliovirus RNA polymerase in infected cells. Proc Natl Acad Sci U S A. 1996;93(6):2296–2301. doi: 10.1073/pnas.93.6.2296
   PubMed Web of Science ®Google Scholar
• Rai DK, Lawrence P, Kloc A, et al. Analysis of the interaction between host factor Sam68 and viral elements during foot-and-mouth disease virus infections. Virol J. 2015;12(1):224. doi: 10.1186/s12985-015-0452-8
   PubMedGoogle Scholar
• Choudhury SM, Ma X, Zeng Z, et al. Senecavirus a 3D interacts with NLRP3 to induce IL-1β production by activating NF-κB and ion channel signals. Microbiol Spectr. 2022;10(2):e02097–21. doi: 10.1128/spectrum.02097-21
   PubMed Web of Science ®Google Scholar
• Zhou Y, Wu W, Xie L, et al. Cellular RNA helicase DDX1 is involved in transmissible gastroenteritis virus nsp14-induced interferon-beta production. Front Immunol. 2017;8. doi: 10.3389/fimmu.2017.00940
   Web of Science ®Google Scholar
• Edgcomb SP, Carmel AB, Naji S, et al. DDX1 is an RNA-dependent ATPase involved in HIV-1 rev function and virus replication. J Mol Biol. 2012;415(1):61–74. doi: 10.1016/j.jmb.2011.10.032
   PubMed Web of Science ®Google Scholar
• Xue Q, Liu H, Zeng Q, et al. The DEAD-Box RNA helicase DDX1 interacts with the viral protein 3D and inhibits foot-and-mouth disease virus replication. Virol Sin. 2019;34(6):610–617. doi: 10.1007/s12250-019-00148-7
   PubMed Web of Science ®Google Scholar
• Sarry M, Caignard G, Dupré J, et al. Host-specific interplay between foot-and-mouth disease virus 3D polymerase and the type-I interferon pathway. Viruses. 2023;15(3):666. doi: 10.3390/v15030666
   PubMed Web of Science ®Google Scholar
• Wang J, Hu Y, Zheng M. Enterovirus A71 antivirals: past, present, and future. Acta Pharm Sin B. 2022;12(4):1542–1566. doi: 10.1016/j.apsb.2021.08.017
   PubMed Web of Science ®Google Scholar
• Hu Y, Musharrafieh R, Zheng M, et al. Enterovirus D68 antivirals: past, present, and future. ACS Infect Dis. 2020;6(7):1572–1586. doi: 10.1021/acsinfecdis.0c00120
   PubMed Web of Science ®Google Scholar
• Laajala M, Reshamwala D, Marjomäki V. Therapeutic targets for enterovirus infections. Expert Opin Ther Targets. 2020;24(8):745–757. doi: 10.1080/14728222.2020.1784141
   PubMed Web of Science ®Google Scholar
• Liang C, Tian L, Liu Y, et al. A promising antiviral candidate drug for the COVID-19 pandemic: a mini-review of remdesivir. Eur J Med Chem. 2020;201:112527. doi: 10.1016/j.ejmech.2020.112527
   PubMed Web of Science ®Google Scholar
• González-Grande R, Jiménez-Pérez M, González Arjona C, et al. New approaches in the treatment of hepatitis C. World J Gastroenterol. 2016;22(4):1421–1432. doi: 10.3748/wjg.v22.i4.1421
   PubMed Web of Science ®Google Scholar
• Crotty S, Maag D, Arnold JJ, et al. The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat Med. 2000;6(12):1375–1379. doi: 10.1038/82191
   PubMed Web of Science ®Google Scholar
• Nikunjkumar P, Tamil Selvan RP, Bhanuprakash V. Ribavirin as a curative and prophylactic agent against foot and mouth disease virus infection in C57BL/6 suckling and adult mice model. Virusdisease. 2021;32(4):737–747. doi: 10.1007/s13337-021-00746-8
   PubMedGoogle Scholar
• Graci Jason D, Harki Daniel A, Korneeva Victoria S, et al. Lethal mutagenesis of poliovirus mediated by a mutagenic pyrimidine analogue. J Virol. 2007;81(20):11256–11266. doi: 10.1128/JVI.01028-07
   PubMed Web of Science ®Google Scholar
• Graci JD, Too K, Smidansky ED, et al. Lethal mutagenesis of picornaviruses with N-6-modified purine nucleoside analogues. Antimicrob Agents Chemother. 2008;52(3):971–979. doi: 10.1128/AAC.01056-07
   PubMed Web of Science ®Google Scholar
• Harki DA, Graci JD, Galarraga JE, et al. Synthesis and antiviral activity of 5-substituted cytidine analogues: identification of a potent inhibitor of viral RNA-dependent RNA polymerases. J Med Chem. 2006;49(21):6166–6169. doi: 10.1021/jm060872x
   PubMed Web of Science ®Google Scholar
• Yin Z, Chen Y-L, Schul W, et al. An adenosine nucleoside inhibitor of dengue virus. Proc Natl Acad Sci U S A. 2009;106(48):20435–20439. doi: 10.1073/pnas.0907010106
   PubMed Web of Science ®Google Scholar
• Deng C-L, Yeo H, Ye H-Q, et al. Inhibition of enterovirus 71 by adenosine analog NITD008. J Virol. 2014;88(20):11915–11923. doi: 10.1128/JVI.01207-14
   PubMed Web of Science ®Google Scholar
• Shang L, Wang Y, Qing J, et al. An adenosine nucleoside analogue NITD008 inhibits EV71 proliferation. Antiviral Res. 2014;112:47–58. doi: 10.1016/j.antiviral.2014.10.009
   PubMed Web of Science ®Google Scholar
• Yan L, Cao R, Zhang H, et al. Design, synthesis and evaluation of 2’-acetylene-7-deaza-adenosine phosphoamidate derivatives as anti-EV71 and anti-EV-D68 agents. Eur J Med Chem. 2021;226:113852. doi: 10.1016/j.ejmech.2021.113852
   PubMed Web of Science ®Google Scholar
• Zhang Z, Yang E, Hu C, et al. Cell-based high-throughput screening assay identifies 2‘,2’-difluoro-2’-deoxycytidine gemcitabine as a potential antipoliovirus agent. ACS Infect Dis. 2017;3(1):45–53. doi: 10.1021/acsinfecdis.6b00116
   PubMed Web of Science ®Google Scholar
• Zheng L, Wang Q, Yang X, et al. Antiviral activity of Fnc, 2’-deoxy-2’-β-fluoro-4’-azidocytidine, against human and duck HBV replication. Antivir Ther. 2012;17(4):679–687. doi: 10.3851/IMP2094
   PubMed Web of Science ®Google Scholar
• Wang R-R, Yang Q-H, Luo R-H, et al. Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. PLoS One. 2014;9(8):e105617. doi: 10.1371/journal.pone.0105617
   PubMed Web of Science ®Google Scholar
• Xu N, Yang J, Zheng B, et al. The pyrimidine analog FNC potently inhibits the replication of multiple enteroviruses. J Virol. 2020;94(9):e00204–20. doi: 10.1128/JVI.00204-20
   PubMed Web of Science ®Google Scholar
• Brown AJ, Won JJ, Graham RL, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res. 2019;169:104541. doi: 10.1016/j.antiviral.2019.104541
   PubMed Web of Science ®Google Scholar
• Warren TK, Jordan R, Lo MK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016;531(7594):381–385. doi: 10.1038/nature17180
   PubMed Web of Science ®Google Scholar
• Ye W, Yao M, Dong Y, et al. Remdesivir (GS-5734) impedes enterovirus replication through viral RNA synthesis inhibition. Front Microbiol. 2020;11:1105. doi: 10.3389/fmicb.2020.01105
   PubMed Web of Science ®Google Scholar
• Bermingham WH, Canning B, Wilton T, et al. Case report: clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection. Front Immunol. 2023;14:1135834. doi: 10.3389/fimmu.2023.1135834
   PubMed Web of Science ®Google Scholar
• Nishi T, Fukai K, Masujin K, et al. Administration of the antiviral agent T-1105 fully protects pigs from foot-and-mouth disease infection. Antiviral Res. 2022;208:105425. doi: 10.1016/j.antiviral.2022.105425
   PubMed Web of Science ®Google Scholar
• Furuta Y, Gowen BB, Takahashi K, et al. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res. 2013;100(2):446–454. doi: 10.1016/j.antiviral.2013.09.015
   PubMed Web of Science ®Google Scholar
• Lumby CK, Zhao L, Oporto M, et al. Favipiravir and zanamivir cleared infection with influenza B in a severely immunocompromised child. Clin Infect Dis. 2020;71(7):e191–e194. doi: 10.1093/cid/ciaa023
   PubMed Web of Science ®Google Scholar
• Sasaki-Tanaka R, Shibata T, Okamoto H, et al. Favipiravir inhibits hepatitis a virus infection in human hepatocytes. Int J Mol Sci. 2022;23(5):2631. doi: 10.3390/ijms23052631
   PubMed Web of Science ®Google Scholar
• Kempf Brian J, Watkins Colleen L, Peersen Olve B, et al. Picornavirus RNA recombination counteracts error catastrophe. J Virol. 2019;93(14):e00652–19. doi: 10.1128/JVI.00652-19
   PubMed Web of Science ®Google Scholar
• Sierra S, Dávila M, Lowenstein PR, et al. Response of foot-and-mouth disease virus to increased mutagenesis: influence of viral load and fitness in loss of infectivity. J Virol. 2000;74(18):8316–8323. doi: 10.1128/JVI.74.18.8316-8323.2000
   PubMed Web of Science ®Google Scholar
• Pariente N, Airaksinen A, Domingo E. Mutagenesis versus inhibition in the efficiency of extinction of foot-and-mouth disease virus. J Virol. 2003;77(12):7131–7138. doi: 10.1128/JVI.77.12.7131-7138.2003
   PubMed Web of Science ®Google Scholar
• Agudo R, Arias A, Pariente N, et al. Molecular characterization of a dual inhibitory and mutagenic activity of 5-fluorouridine triphosphate on viral RNA synthesis. Implications for lethal mutagenesis. J Mol Biol. 2008;382(3):652–666. doi: 10.1016/j.jmb.2008.07.033
   PubMed Web of Science ®Google Scholar
• Farhat A, Malecki E, Bonaterra GA, et al. Cytostatic/cytotoxic effects of 5-fluorouridine nucleolipids on colon, hepatocellular, and renal carcinoma cells: In vitro identification of a potential cytotoxic multi-anticancer drug. Chem Biodivers. 2014;11(3):469–482. doi: 10.1002/cbdv.201300347
   PubMed Web of Science ®Google Scholar
• Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006;16(1):37–48. doi: 10.1002/rmv.483
   PubMed Web of Science ®Google Scholar
• De la Torre JC, Alarcón B, Martínez-Salas E, et al. Ribavirin cures cells of a persistent infection with foot-and-mouth disease virus in vitro. J Virol. 1987;61(1):233–235. doi: 10.1128/jvi.61.1.233-235.1987
   PubMed Web of Science ®Google Scholar
• Choi JH, Jeong K, Kim SM, et al. Synergistic effect of ribavirin and vaccine for protection during early infection stage of foot-and-mouth disease. J Vet Sci. 2018;19(6):788–797. doi: 10.4142/jvs.2018.19.6.788
   PubMed Web of Science ®Google Scholar
• Crotty S, Cameron CE, Andino R. RNA virus error catastrophe: direct molecular test by using ribavirin. Proc Natl Acad Sci U S A. 2001;98(12):6895–6900. doi: 10.1073/pnas.111085598
   PubMed Web of Science ®Google Scholar
• Vignuzzi M, Stone JK, Andino R. Ribavirin and lethal mutagenesis of poliovirus: molecular mechanisms, resistance and biological implications. Virus Res. 2005;107(2):173–181. doi: 10.1016/j.virusres.2004.11.007
   PubMed Web of Science ®Google Scholar
• Wu R, Smidansky ED, Oh HS, et al. Synthesis of a 6-methyl-7-deaza analogue of adenosine that potently inhibits replication of polio and dengue viruses. J Med Chem. 2010;53(22):7958–7966. doi: 10.1021/jm100593s
   PubMed Web of Science ®Google Scholar
• Carroll SS, Tomassini JE, Bosserman M, et al. Inhibition of hepatitis C virus RNA replication by 2’-modified nucleoside analogs. J Biol Chem. 2003;278(14):11979–11984. doi: 10.1074/jbc.M210914200
   PubMed Web of Science ®Google Scholar
• Goris N, De Palma A, Toussaint J-F, et al. 2’-C-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus. Antiviral Res. 2007;73(3):161–168. doi: 10.1016/j.antiviral.2006.09.007
   PubMed Web of Science ®Google Scholar
• Lanko K, Ma Y, Delang L, et al. Antiviral effects of selected nucleoside analogues against human parechoviruses A1 and A3. Antiviral Res. 2019;162:51–53. doi: 10.1016/j.antiviral.2018.12.009
   PubMed Web of Science ®Google Scholar
• Masmoudi F, Santos-Ferreira N, Pajkrt D, et al. Evaluation of 3D human intestinal organoids as a platform for EV-A71 antiviral drug discovery. Cells. 2023;12(8):1138. doi: 10.3390/cells12081138
   PubMed Web of Science ®Google Scholar
• Harrison DN, Gazina EV, Purcell DF, et al. Amiloride derivatives inhibit coxsackievirus B3 RNA replication. J Virol. 2008;82(3):1465–1473. doi: 10.1128/JVI.01374-07
   PubMed Web of Science ®Google Scholar
• Gazina EV, Smidansky ED, Holien JK, et al. Amiloride is a competitive inhibitor of coxsackievirus B3 RNA polymerase. J Virol. 2011;85(19):10364–10374. doi: 10.1128/JVI.05022-11
   PubMed Web of Science ®Google Scholar
• Ogram SA, Boone CD, McKenna R, et al. Amiloride inhibits the initiation of coxsackievirus and poliovirus RNA replication by inhibiting VPg uridylylation. Virology. 2014;464-465:87–97. doi: 10.1016/j.virol.2014.06.025
   PubMed Web of Science ®Google Scholar
• Holien JK, Gazina EV, Elliott RW, et al. Computational analysis of amiloride analogue inhibitors of coxsackievirus B3 RNA polymerase. J Proteomics Bioinform. 2014;s9(Suppl 9):004. doi: 10.4172/jpb.S9-004
   Google Scholar
• Levi LI, Gnädig NF, Beaucourt S, et al. Fidelity variants of RNA dependent RNA polymerases uncover an indirect, mutagenic activity of amiloride compounds. PLoS Path. 2010;6(10):e1001163. doi: 10.1371/journal.ppat.1001163
   PubMed Web of Science ®Google Scholar
• Gong M-J, Chang Y-Y, Shao J, et al. Antiviral effect of amiloride on replication of foot and mouth disease virus in cell culture. Microbial Pathogenesis. 2019;135:103638. doi: 10.1016/j.micpath.2019.103638
   PubMed Web of Science ®Google Scholar
• Chern J-H, Shia K-S, Hsu T-A, et al. Design, synthesis, and structure-activity relationships of pyrazolo[3,4-d]pyrimidines: a novel class of potent enterovirus inhibitors. Bioorg Med Chem Lett. 2004;14(10):2519–2525. doi: 10.1016/j.bmcl.2004.02.092
   PubMed Web of Science ®Google Scholar
• Chen T-C, Chang H-Y, Lin P-F, et al. Novel antiviral agent DTriP-22 targets RNA-dependent RNA polymerase of enterovirus 71. Antimicrob Agents Chemother. 2009;53(7):2740–2747. doi: 10.1128/AAC.00101-09
   PubMed Web of Science ®Google Scholar
• Hung H-C, Chen T-C, Fang M-Y, et al. Inhibition of enterovirus 71 replication and the viral 3D polymerase by aurintricarboxylic acid. J Antimicrob Chemother. 2010;65(4):676–683. doi: 10.1093/jac/dkp502
   PubMed Web of Science ®Google Scholar
• Durk RC, Singh K, Cornelison CA, et al. Inhibitors of foot and mouth disease virus targeting a novel pocket of the RNA-dependent RNA polymerase. PloS One. 2010;5(12):e15049. doi: 10.1371/journal.pone.0015049
   PubMed Web of Science ®Google Scholar
• Rai DK, Schafer EA, Singh K, et al. Repeated exposure to 5D9, an inhibitor of 3D polymerase, effectively limits the replication of foot-and-mouth disease virus in host cells. Antiviral Res. 2013;98(3):380–385. doi: 10.1016/j.antiviral.2013.03.022
   PubMed Web of Science ®Google Scholar
• van der Linden L, Vives-Adrián L, Selisko B, et al. The RNA template channel of the RNA-dependent RNA polymerase as a target for development of antiviral therapy of multiple genera within a virus family. PloS Path. 2015;11(3):e1004733. doi: 10.1371/journal.ppat.1004733
   PubMed Web of Science ®Google Scholar
• Li L, Wang M, Chen Y, et al. Structure of the enterovirus D68 RNA-dependent RNA polymerase in complex with NADPH implicates an inhibitor binding site in the RNA template tunnel. J Struct Biol. 2020;211(1):107510. doi: 10.1016/j.jsb.2020.107510
   PubMed Web of Science ®Google Scholar
• Campagnola G, Gong P, Peersen OB. High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors. Antiviral Res. 2011;91(3):241–251. doi: 10.1016/j.antiviral.2011.06.006
   PubMed Web of Science ®Google Scholar
• Hsu J-A, Yeh J-Y, Lin T-J, et al. Identification of BPR3P0128 as an inhibitor of cap-snatching activities of influenza virus. Antimicrob Agents Chemother. 2012;56(2):647–657. doi: 10.1128/AAC.00125-11
   PubMed Web of Science ®Google Scholar
• Velu AB, Chen G-W, Hsieh P-T, et al. BPR-3P0128 inhibits RNA-dependent RNA polymerase elongation and VPg uridylylation activities of enterovirus 71. Antiviral Res. 2014;112:18–25. doi: 10.1016/j.antiviral.2014.10.003
   PubMed Web of Science ®Google Scholar
• Wishart DS, Feunang YD, Guo AC, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018;46(D1):D1074–D1082. doi: 10.1093/nar/gkx1037
   PubMed Web of Science ®Google Scholar
• Theerawatanasirikul S, Lueangaramkul V, Semkum P, et al. Antiviral mechanisms of sorafenib against foot-and-mouth disease virus via c-RAF and AKT/PI3K pathways. Vet Res Commun. 2023;48(1):329–343. doi: 10.1007/s11259-023-10211-0
   PubMed Web of Science ®Google Scholar
• Liu X, Xu Z, Liang J, et al. Identification of a novel acylthiourea-based potent broad-spectrum inhibitor for enterovirus 3D polymerase in vitro and in vivo. Antiviral Res. 2023;213:105583. doi: 10.1016/j.antiviral.2023.105583
   PubMed Web of Science ®Google Scholar
• Jeong K-W, Lee J-H, Park S-M, et al. Synthesis and in-vitro evaluation of 2-amino-4-arylthiazole as inhibitor of 3D polymerase against foot-and-mouth disease (FMD). European Journal Of Medicinal Chemistry. 2015;102:387–397. doi: 10.1016/j.ejmech.2015.08.020
   PubMed Web of Science ®Google Scholar
• Theerawatanasirikul S, Semkum P, Lueangaramkul V, et al. Non-nucleoside inhibitors decrease foot-and-mouth disease virus replication by blocking the viral 3Dpol. Viruses. 2023;15(1):124. doi: 10.3390/v15010124
   Web of Science ®Google Scholar
• Lanko K, Shi C, Patil S, et al. Assessing in vitro resistance development in enterovirus A71 in the context of combination antiviral treatment. ACS Infect Dis. 2021;7(10):2801–2806. doi: 10.1021/acsinfecdis.0c00872
   PubMed Web of Science ®Google Scholar
• Hu Q, Sun W, Wang C, et al. Recent advances of cocktail chemotherapy by combination drug delivery systems. Adv Drug Deliv Rev. 2016;98:19–34. doi: 10.1016/j.addr.2015.10.022
   PubMed Web of Science ®Google Scholar