Abstract
Enteroviruses are pathogens responsible for several diseases, being enterovirus A71 (EVA71) the second leading cause of hand, foot, and mouth disease (HFMD), especially in Asia–Pacific countries. HFMD is mostly common in infants and children, with mild symptoms. However, the disease can result in severe nervous system disorders in children as well as in immunosuppressed adults. The virus is highly contagious, and its transmission occurs via fecal–oral, oropharyngeal secretions, and fomites. The EVA71 burdens the healthy systems and economies around the world, however, up to date, there is no antiviral approved to treat infected individuals and the existent vaccines are not available or approved to be used worldwide. In this context, an extensive literature research was conducted to describe and summarize the recent advances in natural and/or synthetic compounds with antiviral activity against EVA71. The summarized data presented here might simply encourage the future studies in EVA71 antiviral development, by encouraging further research encompassing these compounds or even the application of the techniques and technologies to improve or produce new antiviral molecules.
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References
Aizman O, Uhlén P, Lal M, Brismar H, Aperia A (2001) Ouabain, a steroid hormone that signals with slow calcium oscillations. Proc Natl Acad Sci USA 98(23):13420–13424. https://doi.org/10.1073/PNAS.221315298/ASSET/D0BDF067-6191-41ED-BB37-9E1FD531E519/ASSETS/GRAPHIC/PQ2213152004.JPEG
Albulescu IC, Van Hoolwerff M, Wolters LA, Bottaro E, Nastruzzi C, Yang SC, Tsay SC, Hwu JR, Snijder EJ, Van Hemert MJ (2015) Suramin inhibits chikungunya virus replication through multiple mechanisms. Antiviral Res. https://doi.org/10.1016/j.antiviral.2015.06.013
Arango D, Morohashi K, Yilmaz A, Kuramochi K, Parihar A, Brahimaj B, Grotewold E, Doseff AI (2013) Molecular basis for the action of a dietary flavonoid revealed by the comprehensive identification of apigenin human targets. Proc Natl Acad Sci US Am. https://doi.org/10.1073/pnas.1303726110
Arita M, Wakita T, Shimizu H (2008) Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity. J Gen Virol. https://doi.org/10.1099/vir.0.2008/002915-0
Arita M, Takebe Y, Wakita T, Shimizu H (2010) A bifunctional anti-enterovirus compound that inhibits replication and the early stage of enterovirus 71 infection. J Gen Virol. https://doi.org/10.1099/vir.0.023374-0
Arita M, Kojima H, Nagano T, Okabe T, Wakita T, Shimizu H (2011) Phosphatidylinositol 4-kinase III beta is a target of enviroxime-like compounds for antipoliovirus activity. J Virol. https://doi.org/10.1128/jvi.02249-10
Atanasov AG, Zotchev SB, Dirsch VM, Orhan IE, Banach M, Rollinger JM, Barreca D, Weckwerth W, Bauer R, Bayer EA, Majeed M, Bishayee A, Bochkov V, Bonn GK, Braidy N, Bucar F, Cifuentes A, D’Onofrio G, Bodkin M, Supuran CT (2021) Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov 20(3):200–216. https://doi.org/10.1038/s41573-020-00114-z
Aylward FO, Moniruzzaman M (2022) Viral complexity. Biomolecules. https://doi.org/10.3390/BIOM12081061
Baggen J, Thibaut HJ, Strating JRPM, Van Kuppeveld FJM (2018) The life cycle of non-polio enteroviruses and how to target it. Nat Rev Microbiol 16(6):368–381. https://doi.org/10.1038/s41579-018-0005-4
Basavannacharya C, Vasudevan SG (2014) Suramin inhibits helicase activity of NS3 protein of dengue virus in a fluorescence-based high throughput assay format. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2014.09.113
Bauer L, Manganaro R, Zonsics B, Strating JRPM, El Kazzi P, Lorenzo Lopez M, Ulferts R, Van Hoey C, Maté MJ, Langer T, Coutard B, Brancale A, Van Kuppeveld FJM (2019) Fluoxetine inhibits enterovirus replication by targeting the viral 2C protein in a stereospecific manner. ACS Infect Dis. https://doi.org/10.1021/acsinfecdis.9b00179
Bayda S, Adeel M, Tuccinardi T, Cordani M, Rizzolio F (2020) The history of nanoscience and nanotechnology: from chemical-physical applications to nanomedicine. In Mol. https://doi.org/10.3390/molecules25010112
Bernard A, Lacroix C, Cabiddu MG, Neyts J, Leyssen P, Pompei R (2015) Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds. Antiviral Chem Chemother. https://doi.org/10.1177/2040206615589035
Bhattacharya D, Ghosh B, Mukhopadhyay M (2019) Development of nanotechnology for advancement and application in wound healing: a review. In IET Nanobiotechnol. https://doi.org/10.1049/iet-nbt.2018.5312
Binford SL, Maldonado F, Brothers MA, et al (2005) Conservation of amino acids in human rhinovirus 3C protease correlates with broad-spectrum antiviral activity of rupintrivir, a novel human rhinovirus 3C protease inhibitor. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.49.2.619-626.2005
Breuss JM, Atanasov AG, Uhrin P (2019) Resveratrol and its effects on the vascular system. Int J Mol Sci. https://doi.org/10.3390/ijms20071523
Cai J, Feng J, Xie S, Wang F, Xu Q (2014) Laminaria japonica extract, an inhibitor of clavibater michiganense subsp. sepedonicum. PLoS ONE. https://doi.org/10.1371/journal.pone.0094329
Cao Y, Lei E, Li L, Ren J, He X, Yang J, Wang S (2021) Antiviral activity of mulberroside C against enterovirus A71 in vitro and in vivo. Eur J Pharmacol 906:174204. https://doi.org/10.1016/j.ejphar.2021.174204
Casati S, Ottria R, Baldoli E, et al (2011) Effects of cytokinins, cytokinin ribosides and their analogs on the viability of normal and neoplastic human cells. Anticancer Res PMID: 21965753
Cheng G, Montero A, Gastaminza P, et al (2008) A virocidal amphipathic α-helical peptide that inhibits hepatitis C virus infection in vitro. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.0712380105
Cha Y, Erez T, Reynolds IJ, Kumar D, Ross J, Koytiger G, Kusko R, Zeskind B, Risso S, Kagan E, Papapetropoulos S, Grossman I, Laifenfeld D (2018) Drug repurposing from the perspective of pharmaceutical companies. Br J Pharmacol 175(2):168–180. https://doi.org/10.1111/bph.13798
Chen ZF, Mao L, Liu LM, Liu YC, Peng Y, Hong X, Wang HH, Liu HG, Liang H (2011) Potential new inorganic antitumour agents from combining the anticancer traditional Chinese medicine (TCM) matrine with Ga(III), Au(III), Sn(IV) ions, and DNA binding studies. J Inorg Biochem. https://doi.org/10.1016/j.jinorgbio.2010.10.007
Cheng M, Deng J, Yang F, Gong Y, Zhao N, Zhang X (2003) Study on physical properties and nerve cell affinity of composite films from chitosan and gelatin solutions. Biomaterials. https://doi.org/10.1016/S0142-9612(03)00117-0
Cheng ML, Weng SF, Kuo CH, Ho HY (2014) Enterovirus 71 induces mitochondrial reactive oxygen species generation that is required for efficient replication. PLoS ONE. https://doi.org/10.1371/journal.pone.0113234
Coates SJ, Davis MDP, Andersen LK (2019) Temperature and humidity affect the incidence of hand, foot, and mouth disease: a systematic review of the literature – a report from the International Society of Dermatology Climate Change Committee. Int J Dermatol 58(4):388–399. https://doi.org/10.1111/ijd.14188
Dang M, Wang X, Wang Q, Wang Y, Lin J, Sun Y, Li X, Zhang L, Lou Z, Wang J, Rao Z (2014) Molecular mechanism of SCARB2-mediated attachment and uncoating of EV71. Protein Cell 5(9):692–703. https://doi.org/10.1007/s13238-014-0087-3
Danthi P, Tosteson M, Li Q, Chow M (2003) Genome delivery and ion channel properties are altered in VP4 mutants of poliovirus. J Virol 77(9):5266–5274. https://doi.org/10.1128/jvi.77.9.5266-5274.2003
De Jong WH, Borm PJA (2008) Drug delivery and nanoparticles: applications and hazards. Int J Nanomed. https://doi.org/10.2147/ijn.s596
De Colibus L, Wang X, Spyrou JAB, Kelly J, Ren J, Grimes J, Puerstinger G, Stonehouse N, Walter TS, Hu Z, Wang J, Li X, Peng W, Rowlands DJ, Fry EE, Rao Z, Stuart DI (2014) More-powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules. Nat Struct Mol Biol. https://doi.org/10.1038/nsmb.2769
Deng C-L, Yeo H, Ye H-Q, et al (2014) Inhibition of Enterovirus 71 by Adenosine Analog NITD008. Journal of Virology 88:11915–11923. https://doi.org/10.1128/jvi.01207-14
De Meyer N, Haemers A, Pieters LAC, Vanden Berghe DA, Vlietinck AJ, Mishra L, Pandey HK (1991) 4′-Hydroxy-3-methoxyflavones with potent antipicornavirus activity. J Med Chem. https://doi.org/10.1021/jm00106a039
De Palma AM, Vliegen I, De Clercq E, Neyts J (2008) Selective inhibitors of picornavirus replication. Med Res Rev. https://doi.org/10.1002/med.20125
Drenichev MS, Oslovsky VE, Sun L, Tijsma A, Kurochkin NN, Tararov VI, Chizhov AO, Neyts J, Pannecouque C, Leyssen P, Mikhailov SN (2016) Modification of the length and structure of the linker of N6-benzyladenosine modulates its selective antiviral activity against enterovirus 71. Eur J Med Chem 111:84–94. https://doi.org/10.1016/j.ejmech.2016.01.036
Du N, Li XH, Bao WG, Wang B, Xu G, Wang F (2019) Resveratrol-loaded nanoparticles inhibit enterovirus 71 replication through the oxidative stress-mediated ERS/autophagy pathway. Int J Mol Med 44(2):737–749. https://doi.org/10.3892/ijmm.2019.4211
Everts M, Cihlar T, Bostwick JR, Whitley RJ (2017) Accelerating drug development: antiviral therapies for emerging viruses as a model. Annu Rev Pharmacol Toxicol 57:155–169. https://doi.org/10.1146/annurev-pharmtox-010716-104533
Filardo S, Di Pietro M, Mastromarino P, Sessa R (2020) Therapeutic potential of resveratrol against emerging respiratory viral infections. Pharmacol Ther. https://doi.org/10.1016/j.pharmthera.2020.107613
Fraser JE, Wang C, Chan KWK, Vasudevan SG, Jans DA (2016) Novel dengue virus inhibitor 4-HPR activates ATF4 independent of protein kinase R-like endoplasmic reticulum kinase and elevates levels of eIF2α phosphorylation in virus infected cells. Antiviral Res 130:1–6. https://doi.org/10.1016/j.antiviral.2016.03.006
Galiniak S, Aebisher D, Bartusik-Aebisher D (2019) Health benefits of resveratrol administration. Acta Biochim Pol. https://doi.org/10.18388/abp.2018_2749
Garson JA, Lubach D, Passas J, Whitby K, Grant PR (1999) Suramin blocks hepatitis C binding to human hepatoma cells in vitro. J Med Virol. https://doi.org/10.1002/(SICI)1096-9071(199903)57:3%3c238::AID-JMV5%3e3.0.CO;2-G
Gunaseelan S, Wong KZ, Min N, Sun J, Ismail NKBM, Tan YJ, Lee RCH, Chu JJH (2019) Prunin suppresses viral IRES activity and is a potential candidate for treating enterovirus A71 infection. Sci Transl Med. https://doi.org/10.1126/SCITRANSLMED.AAR5759
Habermann E (1972) Bee and wasp venoms. Science. https://doi.org/10.1126/science.177.4046.314
Han X, Sun N, Wu H, Guo D, Tien P, Dong C, Wu S, Zhou HB (2016) Identification and structure-activity relationships of diarylhydrazides as novel potent and selective human enterovirus inhibitors. J Med Chem 59(5):2139–2150. https://doi.org/10.1021/acs.jmedchem.5b01803
Hsu WJ, Lin MH, Kuo TC, Chou CM, Mi FL, Cheng CH, Lin CW (2020) Fucoidan from Laminaria japonica exerts antitumor effects on angiogenesis and micrometastasis in triple-negative breast cancer cells. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2020.01.256
Huang P-N, Shih S-R (2014) Update on enterovirus 71 infection. Curr Opin Virol 5:98–104. https://doi.org/10.1016/j.coviro.2014.03.007
Huang X, Li J, Hong Y, Jiang C, Wu J, Wu M, Sheng R, Liu H, Sun J, Xin Y, Su W (2022) Antiviral effects of the petroleum ether extract of Tournefortia sibirica L. against enterovirus 71 infection in vitro and in vivo. Front Pharmacol 13:1–12. https://doi.org/10.3389/fphar.2022.999798
Hwang DS, Kim SK, Bae H (2015) Therapeutic effects of bee venom on immunological and neurological diseases. In Toxins. https://doi.org/10.3390/toxins7072413
Ibba R, Carta A, Madeddu S, Caria P, Serreli G, Piras S, Sestito S, Loddo R, Sanna G (2021) Inhibition of enterovirus a71 by a novel 2-phenyl-benzimidazole derivative. Viruses. https://doi.org/10.3390/v13010058
Jardim ACG, Igloi Z, Shimizu JF, et al (2015) Natural compounds isolated from Brazilian plants are potent inhibitors of hepatitis C virus replication in vitro. Antiviral Research 115:39–47. https://doi.org/10.1016/j.antiviral.2014.12.018
Ji P, Chen C, Hu Y, Zhan Z, Pan W, Li R, Li E, Ge HM, Yang G (2015) Antiviral activity of Paulownia tomentosa against enterovirus 71 of hand, foot, and mouth disease. Biol Pharm Bull. https://doi.org/10.1248/bpb.b14-00357
Kang KH, Jang SK, Kim BK, Park MK (1994) Antibacterial phenylpropanoid glycosides from Paulownia tomentosa steud. Arch Pharmacal Res. https://doi.org/10.1007/BF02979128
Kang KH, Huh H, Kim BK, Lee CK (1999) An antiviral furanoquinone from Paulownia tomentosa steud. Phytother Res. https://doi.org/10.1002/(SICI)1099-1573(199911)13:7%3c624::AID-PTR551%3e3.0.CO;2-A
Karimi A, Majlesi M, Rafieian-Kopaei M (2015) Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol 4(1):27
Kawai T, Akira S (2006) Innate immune recognition of viral infection. Nat Immunol. https://doi.org/10.1038/ni1303
Kim H, Lim CY, Lee DB, Seok JH, Kim KH, Chung MS (2020) Inhibitory effects of Laminaria japonica fucoidans against noroviruses. Viruses. https://doi.org/10.3390/v12090997
Kobayashi K, Koike S (2020) Cellular receptors for enterovirus A71. J Biomed Sci 27(1):1–12. https://doi.org/10.1186/S12929-020-0615-9
Komatsu T, Kido N, Sugiyama T, Yokochi T (2013) Antiviral activity of acidic polysaccharides from Coccomyxa gloeobotrydiformi, a green alga, against an in vitro human influenza A virus infection. Immunopharmacol Immunotoxicol. https://doi.org/10.3109/08923973.2012.710636
Kong M, Chen XG, Xing K, Park HJ (2010) Antimicrobial properties of chitosan and mode of action: a state of the art review. Int J Food Microbiol. https://doi.org/10.1016/j.ijfoodmicro.2010.09.012
Lane T, Anantpadma M, Freundlich JS, et al (2019) The Natural Product Eugenol Is an Inhibitor of the Ebola Virus In Vitro. Pharmaceutical Research 36:2–7. https://doi.org/10.1007/s11095-019-2629-0
Lanko K, Shi C, Patil S, Delang L, Matthijnssens J, Mirabelli C, Neyts J (2021) Assessing In vitro resistance development in enterovirus A71 in the context of combination antiviral treatment. ACS Infect Dis 7(10):2801–2806. https://doi.org/10.1021/ACSINFECDIS.0C00872
Laszczyk MN (2009) Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Planta Med. https://doi.org/10.1055/s-0029-1186102. PMID: 19742422
Li P, Yu J, Hao F, He H, Shi X, Hu J, Wang L, Du C, Zhang X, Sun Y, Lin F, Gu Z, Xu D, Chen X, Shen L, Hu G, Li J, Chen S, Xiao W, Lin T (2017) Discovery of potent EV71 capsid inhibitors for treatment of HFMD. ACS Med Chem Lett. https://doi.org/10.1021/acsmedchemlett.7b00188
Lin YC, Chang CH (2014) In vitro inhibition of enterovirus 71 infection with a nickel ion/chitosan microcomposite. Virus Res 190:17–24. https://doi.org/10.1016/j.virusres.2014.06.012
Lin JY, Kung YA, Shih SR (2019a) Antivirals and vaccines for enterovirus A71. J Biomed Sci 26(1):1–10. https://doi.org/10.1186/s12929-019-0560-7
Lin WY, Yu YJ, Jinn TR (2019b) Evaluation of the virucidal effects of rosmarinic acid against enterovirus 71 infection via in vitro and in vivo study. Virol J 16(1):1–9. https://doi.org/10.1186/s12985-019-1203-z
Lin YJ, Chang YC, Hsiao NW, et al (2012) Fisetin and rutin as 3C protease inhibitors of enterovirus A71. Journal of Virological Methods 182:93–98. https://doi.org/10.1016/j.jviromet.2012.03.020
Lin JY, Kung YA, Shih SR (2019) Antivirals and vaccines for Enterovirus A71. J Biomed Sci 26:1–10. https://doi.org/10.1186/s12929-019-0560-7
Lopes N, Ray S, Espada SF, Bomfim WA, Ray B, Faccin-Galhardi LC, Linhares REC, Nozawa C (2017) Green seaweed Enteromorpha compressa (Chlorophyta, Ulvaceae) derived sulphated polysaccharides inhibit herpes simplex virus. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2017.04.043
Lu G, Qi J, Chen Z, et al (2011) Enterovirus 71 and Coxsackievirus A16 3C Proteases: Binding to Rupintrivir and Their Substrates and Anti-Hand, Foot, and Mouth Disease Virus Drug Design. Journal of Virology 85:10319–10331. https://doi.org/10.1128/jvi.00787-11
Lungu II, Grumezescu AM, Volceanov A, Andronescu E (2019) Nanobiomaterials used in cancer therapy: an up-to-date overview. Molecules. https://doi.org/10.3390/molecules24193547
Masoudi-Sobhanzadeh Y, Omidi Y, Amanlou M, Masoudi-Nejad A (2020) Drug databases and their contributions to drug repurposing. Genomics 112:1087–1095. https://doi.org/10.1016/j.ygeno.2019.06.021
Matthews T, Salgo M, Greenberg M, et al (2004) Enfuvirtide: The first therapy to inhibit the entry of HIV-1 into host CD4 lymphocytes. Nat Rev Drug Discov. https://doi.org/10.1038/nrd1331. PMID: 15031735
McMinn PC (2002) An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 26(1):91–107. https://doi.org/10.1111/j.1574-6976.2002.tb00601.x
Moscatelli V, Hnatyszyn O, Acevedo C, Megías J, Alcaraz MJ, Ferraro G (2006) Flavonoids from Artemisia copa with anti-inflammatory activity. Planta Med. https://doi.org/10.1055/s-2005-873177
Mireku EA, Mensah AY, Amponsah IK, et al (2020) Antimicrobial pentacyclic triterpenes and glycosides from the stem bark of Cussonia bancoensis. Nat Prod Res. https://doi.org/10.1080/14786419.2018.1503262
Muzzareli R, Baldassarre V, Conti F, Ferrara P, Biagini G (1988) Biological activity of chitosan: ultrastructural study. Biomaterials 9:247–252
Ng Q, He F, Kwang J (2015) Recent progress towards novel EV71 anti-therapeutics and vaccines. Viruses 7(12):6441–6457. https://doi.org/10.3390/v7122949
Nishimura Y, Shimojima M, Tano Y, Miyamura T, Wakita T, Shimizu H (2009) Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nat Med. https://doi.org/10.1038/nm.1961
Parvathaneni V, Kulkarni NS, Muth A, Gupta V (2019) Drug repurposing: a promising tool to accelerate the drug discovery process. Drug Discov Today 24(10):2076–2085. https://doi.org/10.1016/j.drudis.2019.06.014
Peng T (2010) Strategies for antiviral screening targeting early steps of virus infection. Virologica Sinica 25(4):281–293. https://doi.org/10.1007/s12250-010-3135-z
Peng FH, Zha XQ, Cui SH, Asghar MN, Pan LH, Wang JH, Luo JP (2015) Purification, structure features and anti-atherosclerosis activity of a Laminaria japonica polysaccharide. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2015.09.027
Puenpa J, Wanlapakorn N, Vongpunsawad S, Poovorawan Y (2019) The History of Enterovirus A71 Outbreaks and Molecular Epidemiology in the Asia-Pacific Region. Journal of Biomedical Science 26:1–11. https://doi.org/10.1186/s12929-019-0573-2
Plevka P, Perera R, Yap ML, Cardosa J, Kuhn RJ, Rossmann MG (2013) Structure of human enterovirus 71 in complex with a capsid-binding inhibitor. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.1222379110
Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, Doig A, Guilliams T, Latimer J, McNamee C, Norris A, Sanseau P, Cavalla D, Pirmohamed M (2018) Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 18(1):41–58. https://doi.org/10.1038/nrd.2018.168
Rabea EI, Badawy MET, Stevens CV, Smagghe G, Steurbaut W (2003) Chitosan as antimicrobial agent: applications and mode of action. In Biomacromolecules. https://doi.org/10.1021/bm034130m
Ren P, Zou G, Bailly B, Xu S, Zeng M, Chen X, Shen L, Zhang Y, Guillon P, Arenzana-Seisdedos F, Buchy P, Li J, Von Itzstein M, Li Q, Altmeyer R (2014) The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection - Suramin inhibits EV71 infection in vitro and in vivo. Emerg Microb Infect. https://doi.org/10.1038/emi.2014.60
Romero JR (2001) Pleconaril: a novel antipicornaviral drug. Expert Opin Investig Drugs. https://doi.org/10.1517/13543784.10.2.369
Roy M, Liang L, Xiao X, Feng P, Ye M, Liu J (2018) Lycorine: a prospective natural lead for anticancer drug discovery. Biomed Pharmacother. https://doi.org/10.1016/j.biopha.2018.07.147
Ryu HW, Park YJ, Lee SU, Lee S, Yuk HJ, Seo KH, Kim YU, Hwang BY, Oh SR (2017) Potential anti-inflammatory effects of the fruits of Paulownia tomentosa. J Nat Prod. https://doi.org/10.1021/acs.jnatprod.7b00325
Reddy BU, Mullick R, Kumar A, et al (2018) A natural small molecule inhibitor corilagin blocks HCV replication and modulates oxidative stress to reduce liver damage. Antiviral Research 150:47–59. https://doi.org/10.1016/j.antiviral.2017.12.004
Santos I de A, Grosche VR, Bergamini FRG, et al (2020) Antivirals Against Coronaviruses: Candidate Drugs for SARS-CoV-2 Treatment? Frontiers in Microbiology 11:. https://doi.org/10.3389/fmicb.2020.01818
Sandtner W, Egwolf B, Khalili-Araghi F, Sánchez-Rodríguez JE, Roux B, Bezanilla F, Holmgren M (2011) Ouabain Binding Site in a Functioning Na /K ATPase. J Biol Chem. https://doi.org/10.1074/jbc.M111.267682
Seo JY, Yaneva R, Cresswell P (2011) Viperin: a multifunctional, interferon-inducible protein that regulates virus replication. In Cell Host Microbe. https://doi.org/10.1016/j.chom.2011.11.004
Salgado-Benvindo C, Thaler M, Tas A, Ogando NS, Bredenbeek PJ, Ninaber DK, Wang Y, Hiemstra PS, Snijder EJ, Van Hemert MJ (2020) Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.00900-20
Sun J, Yogarajah T, Lee RCH, Kaur P, Inoue M, Tan YW, Chu JJH. Drug repurposing of pyrimidine analogs as potent antiviral compounds against human enterovirus A71 infection with potential clinical applications. Sci Rep. 2020 May 18;10(1):8159. https://doi.org/10.1038/s41598-020-65152-4.
Shirosaki M, Koyama T (2011) Laminaria japonica as a food for the prevention of obesity and diabetes. Adv Food Nutr Res. https://doi.org/10.1016/B978-0-12-387669-0.00015-6
Strating JRPM, van der Linden L, Albulescu L, Bigay J, Arita M, Delang L, Leyssen P, van der Schaar HM, Lanke KHW, Thibaut HJ, Ulferts R, Drin G, Schlinck N, Wubbolts RW, Sever N, Head SA, Liu JO, Beachy PA, DeMatteis MA, van Kuppeveld FJM (2015) Itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein. Cell Rep. https://doi.org/10.1016/j.celrep.2014.12.054
Shimizu JF, Lima CS, Pereira CMH, et al (2017) Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry. Scientific Reports 7:1–9. https://doi.org/10.1038/s41598-017-16336-y
Son DJ, Lee JW, Lee YH, Song HS, Lee CK, Hong JT (2007) Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol Therapeutics. https://doi.org/10.1016/j.pharmthera.2007.04.004
Song H, Pei X, Liu Z, Shen C, Sun J, Liu Y, Zhou L, Sun F, Xiao X (2023) Pharmacovigilance in China: evolution and future challenges. Br J Clin Pharmacol 89(2):510. https://doi.org/10.1111/BCP.15277
Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH (2010) Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis 10(11):778–790. https://doi.org/10.1016/S1473-3099(10)70194-8
Tan J, George S, Kusov Y, et al (2013) 3C Protease of Enterovirus 68: structure-based design of michael acceptor inhibitors and their broad-spectrum antiviral effects against picornaviruses. J Virol. https://doi.org/10.1128/jvi.01123-12
Tan CW, Chan YF, Sim KM, Tan EL, Poh CL (2012) Inhibition of enterovirus 71 (EV-71) infections by a novel antiviral peptide derived from EV-71 capsid protein VP1. PLoS ONE. https://doi.org/10.1371/journal.pone.0034589
Tan YW, Yam WK, Kooi RJW, Westman J, Arbrandt G, Chu JJH (2021) Novel capsid binder and PI4KIII beta inhibitors for EV-A71 replication inhibition. Sci Rep 11(1):1–11. https://doi.org/10.1038/s41598-021-89271-8
Tan JK, Chen R, Lee RCH, Li F, Dai K, Zhou G-C, Chu JJH (2022) Discovery of novel and rographolid derivatives as antiviral inhibitors against human enterovirus A71. Pharmaceuticals 122(1):1–22. https://doi.org/10.1016/j.bioorg.2022.105683
Tian B, Liu J (2020) Resveratrol: a review of plant sources, synthesis, stability, modification and food application. In J Sci Food Agric. https://doi.org/10.1002/jsfa.10152
Tijsma A, Franco D, Tucker S, et al (2014) The capsid binder vapendavir and the novel protease inhibitor SG85 inhibit enterovirus 71 replication. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/AAC.03328-14
Uddin MB, Lee BH, Nikapitiya C, Kim JH, Kim TH, Lee HC, Kim CG, Lee JS, Kim CJ (2016) Inhibitory effects of bee venom and its components against viruses in vitro and in vivo. J Microbiol 54(12):853–866. https://doi.org/10.1007/s12275-016-6376-1
van der Linden L, Wolthers KC, van Kuppeveld FJM (2015) Replication and inhibitors of enteroviruses and parechoviruses. Viruses 7(8):4529–4562. https://doi.org/10.3390/v7082832
Vestergaard M, Ingmer H (2019) Antibacterial and antifungal properties of resveratrol. Int J Antimicrob Agents. https://doi.org/10.1016/j.ijantimicag.2019.02.015
Wang J, Su H, Zhang T, Du J, Cui S, Yang F, Jin Q (2014a) Inhibition of enterovirus 71 replication by 7-hydroxyflavone and diisopropyl-flavon7-yl phosphate. PLoS ONE. https://doi.org/10.1371/journal.pone.0092565
Wang Y, Qing J, Sun Y, Rao Z (2014b) Suramin inhibits EV71 infection. Antiviral Res 103(1):1–6. https://doi.org/10.1016/j.antiviral.2013.12.008
Wang Y, Li G, Yuan S, Gao Q, Lan K, Altmeyer R, Zou G (2016) In vitro assessment of combinations of enterovirus inhibitors against enterovirus 71. Antimicrob Agents Chemother 60(9):5357–5367. https://doi.org/10.1128/AAC.01073-16
Wang S, Wang W, Hao C, Yunjia Y, Qin L, He M, Mao W (2018) Antiviral activity against enterovirus 71 of sulfated rhamnan isolated from the green alga Monostroma latissimum. Carbohyd Polym. https://doi.org/10.1016/j.carbpol.2018.07.067
Wang H, Guo T, Yang Y, Yu L, Pan X, Li Y (2019) Lycorine derivative LY-55 inhibits EV71 and CVA16 replication through downregulating autophagy. Front Cell Infect Microbiol. https://doi.org/10.3389/fcimb.2019.00277
Wang J, Hu Y, Zheng M (2022) Enterovirus A71 antivirals: past, present, and future. Acta Pharmaceutica Sinica B. https://doi.org/10.1016/j.apsb.2021.08.017
Wang S, Pang Z, Fan H, Tong Y (2023) Advances in anti-EV-A71 drug development research. J Adv Res. https://doi.org/10.1016/j.jare.2023.03.007
Watson KG, Brown RN, Cameron R, et al (2003) An orally bioavailable oxime ether capsid binder with potent activity against human rhinovirus. J Med Chem. https://doi.org/10.1021/jm0202876
Wen X, Sun D, Guo J, et al (2019) Multifunctionality of structural proteins in the enterovirus life cycle. Future Microbiol 14:1147–1157. https://doi.org/10.2217/fmb-2019-0127
Wei C, Zheng C, Sun J, Luo D, Tang Y, Zhang Y, Ke X, Liu Y, Zheng Z, Wang H (2019) Viperin inhibits enterovirus A71 replication by interacting with viral 2C protein. Viruses. https://doi.org/10.3390/v11010013
XingWu K, Yogarajah T, Wing Choy Loe M, Kaur P, Ching Hua Lee R, Keng Mok C, Hao Wong Y, Phuektes P, Sze Yeo L, Chow VT, Wah Tan Y, Jang Hann Chu J (2023) The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses. Acta Pharmaceutica Sinica B. https://doi.org/10.1016/j.apsb.2023.03.015
Wolfram J, Zhu M, Yang Y, et al (2015) Safety of nanoparticles in medicine HHS Public Access This mini-review addresses the safety considerations for nanoparticles in medicine. Curr Drug Targets 16:1671–1681
Xiao S, Tian Z, Wang Y, et al (2018) Recent progress in the antiviral activity and mechanism study of pentacyclic triterpenoids and their derivatives. Med Res Rev https://doi.org/10.1002/med.21484. Epub 2018 Jan 19
Yao H, Liu J, Xu S, et al (2017) The structural modification of natural products for novel drug discovery. Expert Opinion on Drug Discovery 12:121–140. https://doi.org/10.1080/17460441.2016.1272757
Yahi N, Sabatier JM, Nickel P, Mabrouk K, Gonzalez-Scarano F, Fantini J (1994) Suramin inhibits binding of the V3 region of HIV-1 envelope glycoprotein gp120 to galactosylceramide, the receptor for HIV-1 gp120 on human colon epithelial cells. J Biol Chem. https://doi.org/10.1016/S0021-9258(19)51089-4
Yamaguchi K, Honda M, Ikigai H, et al (2002) Inhibitory effects of (-)-epigallocatechin gallate on the life cycle of human immunodeficiency virus type 1 (HIV-1). Antiviral Research 53:19–34. https://doi.org/10.1016/S0166-3542(01)00189-9
Yamayoshi S, Yamashita Y, Li J, Hanagata N, Minowa T, Takemura T, Koike S (2009) Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med. https://doi.org/10.1038/nm.1992
Yamayoshi S, Fujii K, Koike S (2014) Receptors for enterovirus 71. Emerg Microb Infect. https://doi.org/10.1038/emi.2014.49
Yang Y, Xiu J, Zhang X, Zhang L, Yan K, Qin C, Liu J (2012) Antiviral effect of matrine against human enterovirus 71. Molecules. https://doi.org/10.3390/molecules170910370
Yi E-J, Shin Y-J, Kim J-H, Kim T-G, Chang S-Y (2017) Enterovirus 71 infection and vaccines. Clin Exp Vaccine Res 6(1):4. https://doi.org/10.7774/cevr.2017.6.1.4
Younes I, Rinaudo M (2015). Chitin and chitosan preparation from marine sources. Structure, properties and applications. In Marine Drugs https://doi.org/10.3390/md13031133
Yuan J, Shen L, Wu J, Zou X, Gu J, Chen J, Mao L (2018) Enterovirus A71 proteins: structure and function. Front Microbiol. https://doi.org/10.3389/fmicb.2018.00286
Yue Y, Li Z, Li P, Song N, Li B, Lin W, Liu S (2017) Antiviral activity of a polysaccharide from Laminaria japonica against enterovirus 71. Biomed Pharmacother. https://doi.org/10.1016/j.biopha.2017.09.117
Zambelli B, Ciurli S (2013) Nickel and Human Health. Springer Science+Business Media Dordrecht, 321–357
Zeng S, Meng X, Huang Q, et al (2019) Spiramycin and azithromycin, safe for administration to children, exert antiviral activity against enterovirus A71 in vitro and in vivo. International Journal of Antimicrobial Agents. https://doi.org/10.1016/j.ijantimicag.2018.12.009
Zhang G, Zhou F, Gu B, Ding C, Feng D, Xie F, Wang J, Zhang C, Cao Q, Deng Y, Hu W, Yao K (2012) In vitro and in vivo evaluation of ribavirin and pleconaril antiviral activity against enterovirus 71 infection. Adv Virol. https://doi.org/10.1007/s00705-011-1222-6
Zhang W, Tao J, Yang X, Yang Z, Zhang L, Liu H, Wu K, Wu J (2014) Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection. Biochem Biophys Res Commun 449(3):307–312. https://doi.org/10.1016/j.bbrc.2014.05.019
Zhao CH, Xu J, Zhang YQ, Zhao LX, Feng B (2014) Inhibition of human enterovirus 71 replication by pentacyclic triterpenes and their novel synthetic derivatives. Chem Pharm Bull. https://doi.org/10.1248/cpb.c14-00088
Zhou D, Zhao Y, Kotecha A, Fry EE, Kelly JT, Wang X, Rao Z, Rowlands DJ, Ren J, Stuart DI (2019) Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2. Nat Microbiol 4(3):414–419. https://doi.org/10.1038/s41564-018-0319-z
Zhou J, Wei X hua, Chen F you, et al (2017) Anti-inflammatory pentacyclic triterpenes from the stems of Euonymus carnosus. Fitoterapia. https://doi.org/10.1016/j.fitote.2017.01.015
Zhou 2019a and 2019b: Zhou D, Zhao Y, Kotecha A, et al (2019) Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2. Nature Microbiology 4:414–419. https://doi.org/10.1038/s41564-018-0319-z
Zhu QC, Wang Y, Liu YP, Zhang RQ, Li X, Su WH, Long F, Luo XD, Peng T (2011) Inhibition of enterovirus 71 replication by chrysosplenetin and penduletin. Eur J Pharm Sci. https://doi.org/10.1016/j.ejps.2011.08.030
Acknowledgements
SFL and VRG are grateful for Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) scholarship # 88887.703841/2022-00 and # 88887.505971/2020–00, respectively. IAS thanks Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), scholarship #142495/2020–4 and CAPES-Print scholarship #88887.700246/2022-00. ACGJ is grateful to CAPES-Brasil-Prevention and Combat of Outbreaks, Endemics, Epidemics and Pandemics-Finance Code #88881.506794/2020–01 and to FAPEMIG (Minas Gerais Research Foundation APQ-01487-22 and APQ-04686-22) and CAPES-Finance Code 001.
Funding
This is study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, 88887.703841/2022-00,88887.505971/2020–00,Conselho Nacional de Desenvolvimento Científico e Tecnológico, 142495/2020–4, CAPES print, 88887.700246/2022-00, CAPES-Brasil-Prevention and Combat of Outbreaks, Endemics, Epidemics and Pandemics, 88881.506794/2020–01, Fundação de Amparo à Pesquisa do Estado de Minas Gerais, APQ-01487-22.
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Literature research: SFL, IAS, VRG. Drafting of the manuscript: SFL, IAS. Figures: VRG. Design and critical revision: IAS, GCDS and ACGJ. All authors reviewed the manuscript.
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Feferbaum-Leite, S., Santos, I.A., Grosche, V.R. et al. Insights into enterovirus a-71 antiviral development: from natural sources to synthetic nanoparticles. Arch Microbiol 205, 334 (2023). https://doi.org/10.1007/s00203-023-03660-3
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DOI: https://doi.org/10.1007/s00203-023-03660-3