Abstract
In recent years, unexpected outbreaks of infectious diseases caused by emerging and re-emerging viruses have become more frequent, which is possibly due to environmental changes. These outbreaks result in the loss of life and economic hardship. Vaccines and therapeutics should be developed for the prevention and treatment of infectious diseases. In this review, we summarize and discuss the latest progress in the development of small-molecule viral inhibitors against highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, Ebola virus, and Zika virus. These viruses can interfere with the specific steps of viral life cycle by blocking the binding between virus and host cells, disrupting viral endocytosis, disturbing membrane fusion, and interrupting viral RNA replication and translation, thereby demonstrating potent therapeutic effect against various emerging and re-emerging viruses. We also discuss some general strategies for developing small-molecule viral inhibitors.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Pybus OG, Tatem AJ, Lemey P. Virus evolution and transmission in an ever more connected world. Proc Biol Sci 2015; 282(1821): 20142878.
Kuiken T, Fouchier RA, Schutten M, Rimmelzwaan GF, van Amerongen G, van Riel D, Laman JD, de Jong T, van Doornum G, Lim W, Ling AE, Chan PK, Tam JS, Zambon MC, Gopal R, Drosten C, van der Werf S, Escriou N, Manuguerra JC, Stöhr K, Peiris JS, Osterhaus AD. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet 2003; 362(9380): 263–270
Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012; 367(19): 1814–1820
Lu L, Liu Q, Du L, Jiang S. Middle East respiratory syndrome coronavirus (MERS-CoV): challenges in identifying its source and controlling its spread. Microbes Infect 2013; 15(8-9): 625–629
World Health Organization. Middle East respiratory syndrome coronavirus (MERS-CoV). Available from: http://www.who.int/emergencies/mers-cov/en/(Accessed on June 19, 2017)
World Health Organization. Ebola Situation Reports. Available from: http://apps.who.int/ebola/ebola-situation-reports (Accessed on March 27, 2016)
World Health Organization. Media centre: Zika virus. Available from: http://www.who.int/mediacentre/factsheets/zika/en/(Accessed on September 6, 2016)
Ma W, Li S, Ma S, Jia L, Zhang F, Zhang Y, Zhang J, Wong G, Zhang S, Lu X, Liu M, Yan J, Li W, Qin C, Han D, Qin C, Wang N, Li X, Gao GF. Zika virus causes testis damage and leads to male infertility in mice. Cell 2016; 167(6): 1511–1524. e1510
Li C, Xu D, Ye Q, Hong S, Jiang Y, Liu X, Zhang N, Shi L, Qin CF, Xu Z. Zika virus disrupts neural progenitor development and leads to microcephaly in mice. Cell Stem Cell 2016; 19(1): 120–126
Wang A, Thurmond S, Islas L, Hui K, Hai R. Zika virus genome biology and molecular pathogenesis. Emerg Microbes Infect 2017; 6(3): e13
Calvet G, Aguiar RS, Melo ASO, Sampaio SA, de Filippis I, Fabri A, Araujo ESM, de Sequeira PC, de Mendonça MCL, de Oliveira L, Tschoeke DA, Schrago CG, Thompson FL, Brasil P, Dos Santos FB, Nogueira RMR, Tanuri A, de Filippis AMB. Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis 2016; 16(6): 653–660
Goodfellow FT, Tesla B, Simchick G, Zhao Q, Hodge T, Brindley MA, Stice SL. Zika virus induced mortality and microcephaly in chicken embryos. Stem Cells Dev 2016; 25(22): 1691–1697
Schuler-Faccini L, Ribeiro EM, Feitosa IM, Horovitz DD, Cavalcanti DP, Pessoa A, Doriqui MJ, Neri JI, Neto JM, Wanderley HY, Cernach M, El-Husny AS, Pone MV, Serao CL, Sanseverino MT; Brazilian Medical Genetics Society–Zika Embryopathy Task Force. Possible association between Zika virus infection and microcephaly — Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016; 65(3): 59–62
De Clercq E, Li G. Approved antiviral drugs over the past 50 years. Clin Microbiol Rev 2016; 29(3): 695–747
de Haan CA, Rottier PJ. Molecular interactions in the assembly of coronaviruses. Adv Virus Res 2005; 64: 165–230
Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426(6965): 450–454
Matsuyama S, Ujike M, Morikawa S, Tashiro M, Taguchi F. Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection. Proc Natl Acad Sci USA 2005; 102(35): 12543–12547
Lu L, Liu Q, Zhu Y, Chan KH, Qin L, Li Y, Wang Q, Chan JF, Du L, Yu F, Ma C, Ye S, Yuen KY, Zhang R, Jiang S. Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor. Nat Commun 2014; 5: 3067
Xia S, Liu Q, Wang Q, Sun Z, Su S, Du L, Ying T, Lu L, Jiang S. Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein. Virus Res 2014; 194: 200–210
Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. The spike protein of SARS-CoV—a target for vaccine and therapeutic development. Nat Rev Microbiol 2009; 7(3): 226–236
Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013; 495(7440): 251–254
Shirato K, Kawase M, Matsuyama S. Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2. J Virol 2013; 87(23): 12552–12561
Liu Q, Xia S, Sun Z, Wang Q, Du L, Lu L, Jiang S. Testing of Middle East respiratory syndrome coronavirus replication inhibitors for the ability to block viral entry. Antimicrob Agents Chemother 2015; 59(1): 742–744
Hu H, Li L, Kao RY, Kou B, Wang Z, Zhang L, Zhang H, Hao Z, Tsui WH, Ni A, Cui L, Fan B, Guo F, Rao S, Jiang C, Li Q, Sun M, He W, Liu G. Screening and identification of linear B-cell epitopes and entry-blocking peptide of severe acute respiratory syndrome (SARS)-associated coronavirus using synthetic overlapping peptide library. J Comb Chem 2005; 7(5): 648–656
Han DP, Penn-Nicholson A, Cho MW. Identification of critical determinants on ACE2 for SARS-CoV entry and development of a potent entry inhibitor. Virology 2006; 350(1): 15–25
de Wilde AH, Jochmans D, Posthuma CC, Zevenhoven-Dobbe JC, van Nieuwkoop S, Bestebroer TM, van den Hoogen BG, Neyts J, Snijder EJ. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother 2014; 58(8): 4875–4884
Yi L, Li Z, Yuan K, Qu X, Chen J, Wang G, Zhang H, Luo H, Zhu L, Jiang P, Chen L, Shen Y, Luo M, Zuo G, Hu J, Duan D, Nie Y, Shi X, Wang W, Han Y, Li T, Liu Y, Ding M, Deng H, Xu X. Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells. J Virol 2004; 78(20): 11334–11339
Liu S, Xiao G, Chen Y, He Y, Niu J, Escalante CR, Xiong H, Farmar J, Debnath AK, Tien P, Jiang S. Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors. Lancet 2004; 363(9413): 938–947
Channappanavar R, Lu L, Xia S, Du L, Meyerholz DK, Perlman S, Jiang S. Protective effect of intranasal regimens containing peptidic Middle East respiratory syndrome coronavirus fusion inhibitor against MERS-CoV infection. J Infect Dis 2015; 212(12): 1894–1903
Lu L, Xia S, Ying T, Jiang S. Urgent development of effective therapeutic and prophylactic agents to control the emerging threat of Middle East respiratory syndrome (MERS). Emerg Microbes Infect 2015; 4(6): e37
Zhao H, Zhou J, Zhang K, Chu H, Liu D, Poon VK, Chan CC, Leung HC, Fai N, Lin YP, Zhang AJ, Jin DY, Yuen KY, Zheng BJ. A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses. Sci Rep 2016; 6(1): 22008
Chu LH, Chan SH, Tsai SN, Wang Y, Cheng CH, Wong KB, Waye MM, Ngai SM. Fusion core structure of the severe acute respiratory syndrome coronavirus (SARS-CoV): in search of potent SARSCoV entry inhibitors. J Cell Biochem 2008; 104(6): 2335–2347
Zhao G, Du L, Ma C, Li Y, Li L, Poon VK, Wang L, Yu F, Zheng BJ, Jiang S, Zhou Y. A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV. Virol J 2013; 10(1): 266
Simmons G, Gosalia DN, Rennekamp AJ, Reeves JD, Diamond SL, Bates P. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc Natl Acad Sci USA 2005; 102(33): 11876–11881
Shah PP, Wang T, Kaletsky RL, Myers MC, Purvis JE, Jing H, Huryn DM, Greenbaum DC, Smith AB 3rd, Bates P, Diamond SL. A small-molecule oxocarbazate inhibitor of human cathepsin L blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293T cells. Mol Pharmacol 2010; 78(2): 319–324
Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J, Johnson RF, Olinger GG Jr, Jahrling PB, Laidlaw M, Johansen LM, Lear-Rooney CM, Glass PJ, Hensley LE, Frieman MB. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother 2014; 58(8): 4885–4893
Li T, Zhang Y, Fu L, Yu C, Li X, Li Y, Zhang X, Rong Z, Wang Y, Ning H, Liang R, Chen W, Babiuk LA, Chang Z. siRNA targeting the leader sequence of SARS-CoV inhibits virus replication. Gene Ther 2005; 12(9): 751–761
Li BJ, Tang Q, Cheng D, Qin C, Xie FY, Wei Q, Xu J, Liu Y, Zheng BJ, Woodle MC, Zhong N, Lu PY. Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque. Nat Med 2005; 11(9): 944–951
Chan JF, Chan KH, Kao RY, To KK, Zheng BJ, Li CP, Li PT, Dai J, Mok FK, Chen H, Hayden FG, Yuen KY. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Infect 2013; 67(6): 606–616
Adedeji AO, Singh K, Kassim A, Coleman CM, Elliott R, Weiss SR, Frieman MB, Sarafianos SG. Evaluation of SSYA10-001 as a replication inhibitor of severe acute respiratory syndrome, mouse hepatitis, and Middle East respiratory syndrome coronaviruses. Antimicrob Agents Chemother 2014; 58(8): 4894–4898
Wang H, Xue S, Yang H, Chen C. Recent progress in the discovery of inhibitors targeting coronavirus proteases. Virol Sin 2016; 31(1): 24–30
Báez-Santos YM, Barraza SJ, Wilson MW, Agius MP, Mielech AM, Davis NM, Baker SC, Larsen SD, Mesecar AD. X-ray structural and biological evaluation of a series of potent and highly selective inhibitors of human coronavirus papain-like proteases. J Med Chem 2014; 57(6): 2393–2412
Hoenen T, Groseth A, Falzarano D, Feldmann H. Ebola virus: unravelling pathogenesis to combat a deadly disease. Trends Mol Med 2006; 12(5): 206–215
Mahanty S, Bray M. Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis 2004; 4(8): 487–498
Nanbo A, Imai M, Watanabe S, Noda T, Takahashi K, Neumann G, Halfmann P, Kawaoka Y. Ebolavirus is internalized into host cells via macropinocytosis in a viral glycoprotein-dependent manner. PLoS Pathog 2010; 6(9): e1001121
Hunt CL, Lennemann NJ, Maury W. Filovirus entry: a novelty in the viral fusion world. Viruses 2012; 4(2): 258–275
Noda T, Kolesnikova L, Becker S, Kawaoka Y. The importance of the NP: VP35 ratio in Ebola virus nucleocapsid formation. J Infect Dis 2011; 204(Suppl 3): S878–S883
Noda T, Ebihara H, Muramoto Y, Fujii K, Takada A, Sagara H, Kim JH, Kida H, Feldmann H, Kawaoka Y. Assembly and budding of Ebolavirus. PLoS Pathog 2006; 2(9): e99
Xu W, Luthra P, Wu C, Batra J, Leung DW, Basler CF, Amarasinghe GK. Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis. Nat Commun 2017; 8: 15576
Li H, Yu F, Xia S, Yu Y, Wang Q, Lv M, Wang Y, Jiang S, Lu L. Chemically modified human serum albumin potently blocks entry of Ebola pseudoviruses and viruslike particles. Antimicrob Agents Chemother 2017; 61(4): e02168–16
Li H, Ying T, Yu F, Lu L, Jiang S. Development of therapeutics for treatment of Ebola virus infection. Microbes Infect 2015; 17(2): 109–117
Kleyman TR, Cragoe EJ Jr. Amiloride and its analogs as tools in the study of ion transport. J Membr Biol 1988; 105(1): 1–21
Saeed MF, Kolokoltsov AA, Albrecht T, Davey RA. Cellular entry of Ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes. PLoS Pathog 2010; 6(9): e1001110
Wolf MC, Freiberg AN, Zhang T, Akyol-Ataman Z, Grock A, Hong PW, Li J, Watson NF, Fang AQ, Aguilar HC, Porotto M, Honko AN, Damoiseaux R, Miller JP, Woodson SE, Chantasirivisal S, Fontanes V, Negrete OA, Krogstad P, Dasgupta A, Moscona A, Hensley LE, Whelan SP, Faull KF, Holbrook MR, Jung ME, Lee B. A broad-spectrum antiviral targeting entry of enveloped viruses. Proc Natl Acad Sci USA 2010; 107(7): 3157–3162
Miller EH, Harrison JS, Radoshitzky SR, Higgins CD, Chi X, Dong L, Kuhn JH, Bavari S, Lai JR, Chandran K. Inhibition of Ebola virus entry by a C-peptide targeted to endosomes. J Biol Chem 2011; 286(18): 15854–15861
Basu A, Li B, Mills DM, Panchal RG, Cardinale SC, Butler MM, Peet NP, Majgier-Baranowska H, Williams JD, Patel I, Moir DT, Bavari S, Ray R, Farzan MR, Rong L, Bowlin TL. Identification of a small-molecule entry inhibitor for filoviruses. J Virol 2011; 85(7): 3106–3119
Shoemaker CJ, Schornberg KL, Delos SE, Scully C, Pajouhesh H, Olinger GG, Johansen LM, White JM. Multiple cationic amphiphiles induce a Niemann-Pick C phenotype and inhibit Ebola virus entry and infection. PLoS One 2013; 8(2): e56265
Johansen LM, DeWald LE, Shoemaker CJ, Hoffstrom BG, Lear-Rooney CM, Stossel A, Nelson E, Delos SE, Simmons JA, Grenier JM, Pierce LT, Pajouhesh H, Lehár J, Hensley LE, Glass PJ, White JM, Olinger GG. A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity. Sci Transl Med 2015; 7(290): 290ra89
Madelain V, Oestereich L, Graw F, Nguyen TH, de Lamballerie X, Mentré F, Günnther S, Guedj J. Ebola virus dynamics in mice treated with favipiravir. Antiviral Res 2015; 123: 70–77
Oestereich L, Lüdtke A, Wurr S, Rieger T, Muñoz-Fontela C, Günther S. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res 2014; 105: 17–21
Warren TK, Wells J, Panchal RG, Stuthman KS, Garza NL, Van Tongeren SA, Dong L, Retterer CJ, Eaton BP, Pegoraro G, Honnold S, Bantia S, Kotian P, Chen X, Taubenheim BR, Welch LS, Minning DM, Babu YS, Sheridan WP, Bavari S. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature 2014; 508(7496): 402–405
Knecht W, Henseling J, Löffler M. Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid. Chem Biol Interact 2000; 124(1): 61–76
Leone G, Voso MT, Teofili L, Lübbert M. Inhibitors of DNA methylation in the treatment of hematological malignancies and MDS. Clin Immunol 2003; 109(1): 89–102
Khan M, Dhanwani R, Patro IK, Rao PV, Parida MM. Cellular IMPDH enzyme activity is a potential target for the inhibition of Chikungunya virus replication and virus induced apoptosis in cultured mammalian cells. Antiviral Res 2011; 89(1): 1–8
Warren TK, Warfield KL, Wells J, Swenson DL, Donner KS, Van Tongeren SA, Garza NL, Dong L, Mourich DV, Crumley S, Nichols DK, Iversen PL, Bavari S. Advanced antisense therapies for postexposure protection against lethal filovirus infections. Nat Med 2010; 16(9): 991–994
Geisbert TW, Lee AC, Robbins M, Geisbert JB, Honko AN, Sood V, Johnson JC, de Jong S, Tavakoli I, Judge A, Hensley LE, Maclachlan I. Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study. Lancet 2010; 375(9729): 1896–1905
Wang Z, Wang P, An J. Zika virus and Zika fever. Virol Sin 2016; 31(2): 103–109
Meertens L, Labeau A, Dejarnac O, Cipriani S, Sinigaglia L, Bonnet-Madin L, Le Charpentier T, Hafirassou ML, Zamborlini A, Cao-Lormeau VM, Coulpier M, Missé D, Jouvenet N, Tabibiazar R, Gressens P, Schwartz O, Amara A. Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses. Cell Reports 2017; 18(2): 324–333
Stiasny K, Heinz FX. Flavivirus membrane fusion. J Gen Virol 2006; 87(Pt 10): 2755–2766
Yi Z, Yuan Z, Rice CM, MacDonald MR. Flavivirus replication complex assembly revealed by DNAJC14 functional mapping. J Virol 2012; 86(21): 11815–11832
Zhao B, Yi G, Du F, Chuang YC, Vaughan RC, Sankaran B, Kao CC, Li P. Structure and function of the Zika virus full-length NS5 protein. Nat Commun 2017; 8: 14762
Mukhopadhyay S, Kuhn RJ, Rossmann MG. A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 2005; 3(1): 13–22
Yu Y, Deng YQ, Zou P, Wang Q, Dai Y, Yu F, Du L, Zhang NN, Tian M, Hao JN, Meng Y, Li Y, Zhou X, Fuk-Woo Chan J, Yuen KY, Qin CF, Jiang S, Lu L. A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses. Nat Commun 2017; 8: 15672
Fernando S, Fernando T, Stefanik M, Eyer L, Ruzek D. An approach for Zika virus inhibition using homology structure of the envelope protein. Mol Biotechnol 2016; 58(12): 801–806
Mounce BC, Cesaro T, Carrau L, Vallet T, Vignuzzi M. Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding. Antiviral Res 2017; 142: 148–157
Rausch K, Hackett BA, Weinbren NL, Reeder SM, Sadovsky Y, Hunter CA, Schultz DC, Coyne CB, Cherry S. Screening bioactives reveals Nanchangmycin as a broad spectrum antiviral active against Zika virus. Cell Reports 2017; 18(3): 804–815
Delvecchio R, Higa LM, Pezzuto P, Valadão AL, Garcez PP, Monteiro FL, Loiola EC, Dias AA, Silva FJ, Aliota MT, Caine EA, Osorio JE, Bellio M, O’Connor DH, Rehen S, de Aguiar RS, Savarino A, Campanati L, Tanuri A. Chloroquine, an endocytosis blocking agent, inhibits Zika virus infection in different cell models. Viruses 2016; 8(12): E322
Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, Tcw J, Kouznetsova J, Ogden SC, Hammack C, Jacob F, Nguyen HN, Itkin M, Hanna C, Shinn P, Allen C, Michael SG, Simeonov A, Huang W, Christian KM, Goate A, Brennand KJ, Huang R, Xia M, Ming GL, Zheng W, Song H, Tang H. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med 2016; 22(10): 1101–1107
Li C, Deng YQ, Wang S, Ma F, Aliyari R, Huang XY, Zhang NN, Watanabe M, Dong HL, Liu P, Li XF, Ye Q, Tian M, Hong S, Fan J, Zhao H, Li L, Vishlaghi N, Buth JE, Au C, Liu Y, Lu N, Du P, Qin FX, Zhang B, Gong D, Dai X, Sun R, Novitch BG, Xu Z, Qin CF, Cheng G. 25-Hydroxycholesterol protects host against Zika virus infection and its associated microcephaly in a mouse model. Immunity 2017; 46(3): 446–456
Lee H, Ren J, Nocadello S, Rice AJ, Ojeda I, Light S, Minasov G, Vargas J, Nagarathnam D, Anderson WF, Johnson ME. Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus. Antiviral Res 2017; 139: 49–58
Cao X, Li Y, Jin X, Li Y, Guo F, Jin T. Molecular mechanism of divalent-metal-induced activation of NS3 helicase and insights into Zika virus inhibitor design. Nucleic Acids Res 2016; 44(21): 10505–10514
Ramharack P, Soliman MES. Zika virus NS5 protein potential inhibitors: an enhanced in silico approach in drug discovery. J Biomol Struct Dyn 2017 Apr 17 [Epub ahead of print] https://doi.org/10.1080/07391102.2017.1313175
Xu HT, Hassounah SA, Colby-Germinario SP, Oliveira M, Fogarty C, Quan Y, Han Y, Golubkov O, Ibanescu I, Brenner B, Stranix BR, Wainberg MA. Purification of Zika virus RNA-dependent RNA polymerase and its use to identify small-molecule Zika inhibitors. J Antimicrob Chemother 2017; 72(3): 727–734
Li Z, Brecher M, Deng YQ, Zhang J, Sakamuru S, Liu B, Huang R, Koetzner CA, Allen CA, Jones SA, Chen H, Zhang NN, Tian M, Gao F, Lin Q, Banavali N, Zhou J, Boles N, Xia M, Kramer LD, Qin CF, Li H. Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction. Cell Res 2017; 27(8): 1046–1064
Zmurko J, Marques RE, Schols D, Verbeken E, Kaptein SJ, Neyts J. The viral polymerase inhibitor 7-deaza-2′-C-methyladenosine is a potent inhibitor of in vitro Zika virus replication and delays disease progression in a robust mouse infection model. PLoS Negl Trop Dis 2016; 10(5): e0004695
Hercík K, Kozak J, Šála M, Dejmek M, Hřebabecký H, Zborníková E, Smola M, Ruzek D, Nencka R, Boura E. Adenosine triphosphate analogs can efficiently inhibit the Zika virus RNA-dependent RNA polymerase. Antiviral Res 2017; 137: 131–133
Deng YQ, Zhang NN, Li CF, Tian M, Hao JN, Xie XP, Shi PY, Qin CF. Adenosine analog NITD008 is a potent inhibitor of Zika virus. Open Forum Infect Dis 2016; 3(4): ofw175
Xie X, Zou J, Shan C, Yang Y, Kum DB, Dallmeier K, Neyts J, Shi PY. Zika virus replicons for drug discovery. EBioMedicine 2016; 12: 156–160
Cui L, Zou P, Chen E, Yao H, Zheng H, Wang Q, Zhu JN, Jiang S, Lu L, Zhang J. Visual and motor deficits in grown-up mice with congenital Zika virus infection. EBioMedicine 2017; 20: 193–201
Zou J, Shi PY. Adulthood sequelae of congenital Zika virus infection in mice. EBioMedicine 2017; 20: 11–12
Lu L, Yu F, Cai L, Debnath AK, Jiang S. Development of smallmolecule HIV entry inhibitors specifically targeting gp120 or gp41. Curr Top Med Chem 2016; 16(10): 1074–1090
Jiang S, Lin K, Strick N, Neurath AR. HIV-1 inhibition by a peptide. Nature 1993; 365(6442): 113
Lalezari JP, Henry K, O’Hearn M, Montaner JS, Piliero PJ, Trottier B, Walmsley S, Cohen C, Kuritzkes DR, Eron JJ Jr, Chung J, DeMasi R, Donatacci L, Drobnes C, Delehanty J, Salgo M; TORO 1 Study Group. Enfuvirtide, an HIV-1 fusion inhibitor, for drugresistant HIV infection in North and South America. N Engl J Med 2003; 348(22): 2175–2185
Su S, Wang Q, Xu W, Yu F, Hua C, Zhu Y, Jiang S, Lu L. A novel HIV-1 gp41 tripartite model for rational design of HIV-1 fusion inhibitors with improved antiviral activity. AIDS 2017; 31(7): 885–894
Acknowledgements
This work was supported by grants from the Shanghai Public Health Clinical Center (Nos. 2016-27 and KY-GW-2017-17), the National Key Research and Development Program of China (Nos. 2016YFC1201000 and 2016YFC1200405 to S. J., 2016YFC-1202901 to L. L.), the Sanming Project of Medicine in Shenzhen to L. L. and S. J., and the Hi-Tech Research and Development Program of China (863 Program) (No. 2015AA020930 to L. L.).We also thank Guangzhou Sagene Biotech Co., Ltd. for its aid in the preparation of the figures.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Wang, X., Zou, P., Wu, F. et al. Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging and re-emerging viruses. Front. Med. 11, 449–461 (2017). https://doi.org/10.1007/s11684-017-0589-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11684-017-0589-5