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dc.contributor.authorFatma B.-
dc.contributor.authorKumar R.-
dc.contributor.authorSingh V.A.-
dc.contributor.authorNehul S.-
dc.contributor.authorSharma R.-
dc.contributor.authorKesari P.-
dc.contributor.authorKuhn R.J.-
dc.contributor.authorTomar, Shailly-
dc.date.accessioned2020-09-30T11:33:00Z-
dc.date.available2020-09-30T11:33:00Z-
dc.date.issued2020-
dc.identifier.citationAntiviral Research(2020), 179(): --
dc.identifier.issn1663542-
dc.identifier.other32380148-
dc.identifier.urihttps://doi.org/10.1016/j.antiviral.2020.104808-
dc.identifier.urihttp://repository.iitr.ac.in/handle/123456789/1178-
dc.description.abstractChikungunya virus (CHIKV) is an arthritogenic alphavirus and currently, no antiviral drug is available to combat it. Capsid protein (CP) of alphaviruses present at the N-terminus of the structural polyprotein possesses auto-proteolytic activity which is essential for initiating the structural polyprotein processing. We are reporting for the first time antiviral molecules targeting capsid proteolytic activity. Structure-assisted drug-repositioning identified three molecules: P1,P4-Di(adenosine-5?) tetraphosphate (AP4), Eptifibatide acetate (EAC) and Paromomycin sulphate (PSU) as potential capsid protease inhibitors. A FRET-based proteolytic assay confirmed anti-proteolytic activity of these molecules. Additionally, in vitro cell-based antiviral studies showed that EAC, AP4, and PSU drastically stifled CHIKV at the post-entry step with a half-maximal effective concentration (EC50) of 4.01 ?M, 10.66 ?M and 22.91 ?M-
dc.description.abstractrespectively. Interestingly, the inhibitors had no adverse effect on viral RNA synthesis and treatment of cells with inhibitors diminished levels of CP in virus-infected cells, which confirmed inhibition of capsid auto-proteolytic activity. In conclusion, the discovery of antiviral molecules targeting capsid protease demystifies the alphavirus capsid protease as a potential target for antiviral drug discovery. © 2020 Elsevier B.V.-
dc.language.isoen_US-
dc.publisherElsevier B.V.-
dc.relation.ispartofAntiviral Research-
dc.subjectAntiviral-
dc.subjectCapsid protein-
dc.subjectChikungunya-
dc.subjectDrug repositioning-
dc.subjectProtease-
dc.titleAlphavirus capsid protease inhibitors as potential antiviral agents for Chikungunya infection-
dc.typeArticle-
dc.scopusid57191071112-
dc.scopusid57209875422-
dc.scopusid57201632985-
dc.scopusid57195303343-
dc.scopusid57209347974-
dc.scopusid57218355625-
dc.scopusid7202460038-
dc.scopusid57203506001-
dc.affiliationFatma, B., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India-
dc.affiliationKumar, R., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India-
dc.affiliationSingh, V.A., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India-
dc.affiliationNehul, S., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India-
dc.affiliationSharma, R., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India-
dc.affiliationKesari, P., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India-
dc.affiliationKuhn, R.J., Department of Biological Sciences, And Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West LafayetteIN, United States-
dc.affiliationTomar, S., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India-
dc.description.fundingThis research was supported by the Science and Engineering Research Board, Department of Science & Technology, Government of India (grant- EMR/2016/004938 ). BF and SN thanks Ministry of Human Resource Development, Government of India for financial support. RK acknowledges support from the Science and Engineering Research Board, Department of Science & Technology, Government of India for National Post-Doctoral Fellowship (grant- PDF/2017/00649 ). VAS, ST and RJK acknowledges Science and Engineering Research Board, Department of Science & Technology, Government of India for OVDF fellowship (grant- SB/S9/Z-03/2017-V (2018–19). We also thank Jacqueline Anderson (Graduate student, Department of Biological Sciences, Purdue University) for her constructive criticism on the manuscript.-
dc.description.correspondingauthorTomar, S.; Department of Biotechnology, Indian Institute of Technology, RoorkeeIndia; email: shailly.tomar@bt.iit.ac.in-
Appears in Collections:Journal Publications [BT]

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