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Current status of therapeutic and vaccine approaches against Zika virus

Published:August 07, 2017DOI:https://doi.org/10.1016/j.ejim.2017.08.001

      Highlights

      • The neuroteratogenic nature of ZIKV infection is posing serious threats to unborn lives.
      • It is necessary to develop an ideal ZIKV prophylactic or therapeutic agent urgently.
      • Monoclonal antibodies and several vaccine approaches against ZIKV are in progress.
      • Anti-viral drugs specifically sofosbuvir hold promise as therapeutics against ZIKV.

      Abstract

      Zika virus (ZIKV) is a global threat because it is spreading at an alarming rate because of its wider range of transmission routes. The neuroteratogenic nature of ZIKV infection is posing serious threats to unborn lives therefore, it is necessary to develop an ideal ZIKV prophylactic or therapeutic agent urgently. Researchers are having tough time finding a treatment for ZIKV in part because of serious consequences of vaccines and drugs to unborn lives and pregnant women. However, in vitro and in vivo evaluation of therapeutic efficacy of DNA vaccine, recombinant subunit vaccine, and ZIKV purified inactivated vaccine offers hope for human protection. Large number of food and drug administration (FDA) approved drugs as wells as compounds with anti-ZIKV activity offer valuable opportunity to control the massive bio-burden of this catastrophic epidemic. Some evidences suggest that immunotherapeutics might prove to be winning strategy in pregnant females. Here, we review the recent advances and current knowledge regarding therapeutic interventions against ZIKV infection. This article will provide baseline data and roadmap to prosecute further research for the development of novel therapeutic strategy to curb the explosive rise in ZIKV.

      Keywords

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      References

        • Cook S.
        • Holmes E.
        A multigene analysis of the phylogenetic relationships among the flaviviruses (family: Flaviviridae) and the evolution of vector transmission.
        Arch Virol. 2006; 151: 309-325
        • Faye O.
        • et al.
        Molecular evolution of Zika virus during its emergence in the 20th century.
        PLoS Negl Trop Dis. 2014; 8e2636
        • Al-Qahtani A.A.
        • et al.
        Zika virus: a new pandemic threat.
        J Infect Dev Ctries. 2016; 10: 201-207
        • Basu R.
        • Tumban E.
        Zika virus on a spreading spree: what we now know that was unknown in the 1950's.
        Virol J. 2016; 13: 165
        • Wahid B.
        • et al.
        Zika: as an emergent epidemic.
        Asian Pac J Trop Med. 2016; 9: 723-729
        • Colt S.
        • et al.
        Transmission of Zika virus through breast milk and other breastfeeding-related bodily-fluids: a systematic review.
        PLoS Negl Trop Dis. 2017; 11e0005528
        • Cao B.
        • Diamond M.S.
        • Mysorekar I.U.
        Maternal-fetal transmission of zika virus: routes and signals for infection.
        J Interf Cytokine Res. 2017; 37: 287-294
        • Barjas-Castro M.L.
        • et al.
        Probable transfusion-transmitted Zika virus in Brazil.
        Transfusion. 2016; 56: 1684-1688
        • World Health Organization (WHO)
        WHO media centre, 2016.
        (Available:)
        • Blázquez A.-B.
        • Saiz J.-C.
        Neurological manifestations of Zika virus infection.
        World Journal of Virology. 2016; 5: 135
        • Barrett A.D.
        Zika vaccine candidates progress through nonclinical development and enter clinical trials. npj.
        Vaccine. 2016; 1: 16023
        • Xu X.
        • et al.
        Identifying candidate targets of immune responses in Zika virus based on homology to epitopes in other Flavivirus species.
        PLoS Currents. 2016; 8
        • Ge L.
        • G T.L.
        Development of recombinant ZIKV vaccine based on subunit envelope (E) antigen fused to TLR5 agonist (flagellin).
        National Institute of Health, 2016
        • Larocca R.A.
        • et al.
        Vaccine protection against Zika virus from Brazil.
        Nature. 2016; 536: 474-478
        • Abbink P.
        • et al.
        Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys.
        Science. 2016; 353: 1129-1132
        • Awasthi S.
        Zika virus: prospects for the development of vaccine and antiviral agents.
        J Antivir Antiretrovir. 2016; 8
        • Narayanan R.
        Zeka virus therapeutics: drug targets and repurposing medicine from the human genome.
        MOJ Proteomics Bioinform. 2016; 300084
        • Narayanan R.
        Zika virus therapeutic lead compounds discovery using chemoinformatics approaches.
        MOJ Proteomics Bioinform. 2016; 300084
        • Kim E.
        • et al.
        Preventative vaccines for Zika virus outbreak: preliminary evaluation.
        EBioMedicine. 2016; 13: 315-320
        • Adcock R.S.
        • et al.
        Evaluation of anti-Zika virus activities of broad-spectrum antivirals and NIH clinical collection compounds using a cell-based, high-throughput screen assay.
        Antivir Res. 2017; 138: 47-56
        • Sacramento C.Q.
        • et al.
        The clinically approved antiviral drug sofosbuvir impairs Brazilian zika virus replication.
        BioRxiv, 2016: 061671
        • Pascoalino B.S.
        • et al.
        Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library.
        F1000Research, 2016: 5
        • Barrows N.J.
        • et al.
        A screen of FDA-approved drugs for inhibitors of Zika virus infection.
        Cell Host Microbe. 2016; 20: 259-270
        • Zhao H.
        • et al.
        Structural basis of Zika virus-specific antibody protection.
        Cell. 2016; 166: 1016-1027
        • Swanstrom J.
        • et al.
        Dengue virus envelope dimer epitope monoclonal antibodies isolated from dengue patients are protective against Zika virus.
        MBio. 2016; 7 (p. e01123-16)
        • Wang S.
        • et al.
        Transfer of convalescent serum to pregnant mice prevents Zika virus infection and microcephaly in offspring.
        Cell Res. 2016; 27: 158-160
        • Ngono A.E.
        • et al.
        Mapping and role of the CD8+ T cell response during primary Zika virus infection in mice.
        Cell Host Microbe. 2017; 21: 35-46
        • Contreras D.
        • Arumugaswami V.
        Zika virus infectious cell culture system and the in vitro prophylactic effect of interferons.
        JoVE (J Vis Exp). 2016; 114: e54767
        • Marston H.D.
        • et al.
        Considerations for developing a Zika virus vaccine.
        N Engl J Med. 2016; 375: 1209-1212
        • Tripp R.A.
        • Ross T.M.
        Development of a Zika vaccine.
        Taylor & Francis, 2016
        • Mukherjee R.
        • Khera A.
        Zika virus: vaccine initiatives and obstacles.
        Medical Journal of Dr DY Patil University. 2017; 10: 10
        • Dawes B.E.
        • et al.
        Research and development of Zika virus vaccines.
        npj Vaccines. 2016; 1: 16007
        • Awasthi S.
        Zika virus: prospects for the development of vaccine and antiviral agents.
        Journal of Antivirals & Antiretrovirals. 2016; 8
        • Thomas S.J.
        • et al.
        Fast-track Zika vaccine development—is it possible?.
        N Engl J Med. 2016; 375: 1212-1216
        • Palacios R.
        • Poland G.A.
        • Kalil J.
        Another emerging arbovirus, another emerging vaccine: targeting Zika virus.
        Vaccine. 2016; 20: 2291-2293
        • Plotkin S.
        Zika as still another argument for a new path to vaccine development.
        Clin Microbiol Infect. 2016; 22: 294-295
        • Gupta A.K.
        • et al.
        ZikaVR: an integrated Zika virus resource for genomics, proteomics, phylogenetic and therapeutic analysis.
        Sci Rep. 2016; 6
        • Pardi N.
        • et al.
        Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.
        Nature. 2017; 543: 248-251
        • Muthumani K.
        • et al.
        In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine.
        npj Vaccines. 2016; 1: 16021
        • Kennedy R.B.
        Pushing forward with Zika vaccines.
        EBioMedicine. 2016; 13: 29-30
        • Villar L.
        • et al.
        Efficacy of a tetravalent dengue vaccine in children in Latin America.
        N Engl J Med. 2015; 372: 113-123
        • Hamdy R.F.
        Efficacy of a tetravalent dengue vaccine in children in Latin America.
        Journal of the Pediatric Infectious Diseases Society. 2015; 4: 389-392
        • Pierson T.C.
        • Graham B.S.
        Zika virus: immunity and vaccine development.
        Cell. 2016; 167: 625-631
        • Viranaicken W.
        • et al.
        Zika research projects list: ZIKAVax project: the exosome technology as promising platform for the development of a candidate vaccine against Zika virus.
        (Abstracts) International ZIKA summit 2016, 2016
        • Turánek J.
        Zika virus is a candidate for application of nanofibre based system for noninvasive sublingual immunisation: new technology platform for printed vaccines.
        International ZIKA summit 2016, 2016
        • Aliota M.T.
        • et al.
        Heterologous protection against Asian Zika virus challenge in rhesus macaques.
        PLoS Negl Trop Dis. 2016; 10e0005168
        • Dyer O.
        Trials of Zika vaccine are set to begin in North America.
        British Medical Journal Publishing Group, 2016
        • Dowd K.A.
        • et al.
        Rapid development of a DNA vaccine for Zika virus.
        Science. 2016; : aai9137
        • Global Research Collaboration for Infectious Disease Preparedness
        Zika Vaccine Working Group Overview.
        • Durbin A.P.
        Vaccine development for Zika virus—timelines and strategies. In seminars in reproductive medicine.
        Thieme Medical Publishers, 2016
        • Whitehorn J.
        • et al.
        Dengue therapeutics, chemoprophylaxis, and allied tools: state of the art and future directions.
        PLoS Negl Trop Dis. 2014; 8e3025
        • Kuivanen S.
        • et al.
        Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism.
        Antivir Res. 2016;
        • Xu M.
        • et al.
        Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen.
        Nat Med. 2016; 22: 1101-1107
        • Kuperman A.A.
        • Koren O.
        Antibiotic use during pregnancy: how bad is it?.
        BMC Med. 2016; 14: 91
        • Bullard-Feibelman K.M.
        • et al.
        The FDA-approved drug sofosbuvir inhibits Zika virus infection.
        Antivir Res. 2017; 137: 134-140
        • Onorati M.
        • et al.
        Zika virus disrupts phospho-TBK1 localization and mitosis in human neuroepithelial stem cells and radial glia.
        Cell Rep. 2016; 16: 2576-2592
        • Goebel S.
        • et al.
        A sensitive virus yield assay for evaluation of antivirals against Zika virus.
        J Virol Methods. 2016; 238: 13-20
        • Eyer L.
        • et al.
        Nucleoside inhibitors of Zika virus.
        J Infect Dis. 2016; 214: 707-711
        • Retallack H.
        • et al.
        Zika virus cell tropism in the developing human brain and inhibition by azithromycin.
        Proc Natl Acad Sci. 2016; 113: 14408-14413
        • Delvecchio R.
        • et al.
        Chloroquine, an endocytosis blocking agent, inhibits Zika virus infection in different cell models.
        Virus. 2016; 8: 322
        • Zmurko J.
        • et al.
        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; 10e0004695
        • Mumtaz N.
        • et al.
        Zika virus: where is the treatment?.
        Current Treatment Options in Infectious Diseases. 2016; 8: 208-211
        • Julander J.G.
        • et al.
        Efficacy of the broad-spectrum antiviral compound BCX4430 against Zika virus in cell culture and in a mouse model.
        Antivir Res. 2017; 137: 14-22
        • Salam A.P.
        • et al.
        Clinical trials of therapeutics for the prevention of congenital Zika virus disease: challenges and potential solutions clinical trials of therapeutics to prevent congenital ZIKV disease.
        Ann Intern Med. 2017; 28: 411-417
        • Saiz J.-C.
        • Martín-Acebes M.A.
        Zika virus: a race in search for antivirals.
        Antimicrob Agents Chemother. 2017; (p. AAC. 00411–17)
        • Carneiro B.M.
        • et al.
        The green tea molecule EGCG inhibits Zika virus entry.
        Virology. 2016; 496: 215-218
        • Li C.
        • et al.
        25-Hydroxycholesterol protects host against Zika virus infection and its associated microcephaly in a mouse model.
        Immunity. 2017; 46: 446-456
        • Sahoo M.
        • et al.
        Virtual screening for potential inhibitors of NS3 protein of Zika virus.
        Genome Inform. 2016; 14: 104-111
        • Barbosa-Lima G.
        • et al.
        2, 8-bis (trifluoromethyl) quinoline analogs show improved anti-Zika virus activity, compared to mefloquine.
        Eur J Med Chem. 2017; 127: 334-340
        • Deng Y.-Q.
        • et al.
        Adenosine analog NITD008 is a potent inhibitor of Zika virus. In Open forum infectious diseases.
        Oxford University Press, 2016
        • Albulescu I.C.
        • et al.
        Suramin inhibits Zika virus replication by interfering with virus attachment and release of infectious particles.
        Antivir Res. 2017; 143: 230-236
        • Tan C.W.
        • et al.
        Polysulfonate suramin inhibits Zika virus infection.
        Antivir Res. 2017; 143: 186-194
        • L C.
        • et al.
        Viral polymerase inhibitors T-705 and T-1105 are potential inhibitors of Zika virus replication.
        Virology. 2017; (ahead of print)https://doi.org/10.1007/s00705-017-3436-8
        • Costa V.V.
        • et al.
        N-methyl‑d-aspartate (NMDA) receptor blockade prevents neuronal death induced by Zika virus infection.
        MBio. 2017; 8e00350-17
        • Fagbami A.
        • et al.
        Cross-infection enhancement among African flaviviruses by immune mouse ascitic fluids.
        Cytobios. 1986; 49: 49-55
        • Sautto G.
        • et al.
        Possible future monoclonal antibody (mAb)-based therapy against arbovirus infections.
        Biomed Res Int. 2013; 2013
        • Balsitis S.J.
        • et al.
        Lethal antibody enhancement of dengue disease in mice is prevented by Fc modification.
        PLoS Pathog. 2010; 6e1000790
        • Sapparapu G.
        • et al.
        Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice.
        Nature. 2016; 540: 443-447
        • Heslop H.E.
        • Leen A.M.
        T-cell therapy for viral infections.
        ASH Education Program Book. 2013; 2013: 342-347
        • Grant A.
        • et al.
        Zika virus targets human STAT2 to inhibit type I interferon signaling.
        Cell Host Microbe. 2016; 19: 882-890
        • Kumar A.
        • et al.
        Zika virus inhibits type-I interferon production and downstream signaling.
        EMBO Rep. 2016; 17: 1766-1775
        • Bayer A.
        • et al.
        Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection.
        Cell Host Microbe. 2016; 19: 705-712
        • Hercík K.
        • et al.
        Adenosine triphosphate analogs can efficiently inhibit the Zika virus RNA-dependent RNA polymerase.
        Antivir Res. 2017; 137: 131-133
        • Lazear H.M.
        • et al.
        A mouse model of Zika virus pathogenesis.
        Cell Host Microbe. 2016; 19: 720-730
        • Sacramento C.Q.
        • et al.
        The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication.
        Sci Rep. 2017; 7: 40920
        • Kuivanen S.
        • et al.
        Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism.
        Antivir Res. 2017; 139: 117-128
        • Rausch K.
        • et al.
        Screening bioactives reveals nanchangmycin as a broad spectrum antiviral active against Zika virus.
        Cell Rep. 2017; 18: 804-815
        • Robbiani D.F.
        • et al.
        Recurrent potent human neutralizing antibodies to Zika virus in Brazil and Mexico.
        Cell. 2017; 169 (e11): 597-609