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Title: Chikungunya virus inhibition by peptidomimetic inhibitors targeting virus-specific cysteine protease
Authors: Singh H.
Mudgal R.
Narwal M.
Kaur R.
Singh V.A.
Malik A.
Chaudhary M.
Tomar, Shailly
Published in: Biochimie
Abstract: Chikungunya virus (CHIKV), a mosquito-borne pathogenic virus that reemerged and caused epidemic in the Indian Ocean island of La Réunion, is a potential public health threat. Currently there is no antiviral drug or vaccine commercially available for the treatment of chikungunya fever, which necessitates the urge for an effective antiviral therapy for chikungunya treatment. In the present study, a FRET based protease assay was used to analyze the proteolytic activity of chikungunya nsP2 protease (CHIKV nsP2pro) - an essential viral enzyme, with fluorogenic substrate peptide. This protease assay was used to assess the inhibitory activity of Pep-I (MMsINC® database ID MMs03131094) and Pep-II (MMsINC® database ID MMs03927237), peptidomimetic compounds identified in a previous study by our group. Both compounds inhibited CHIKV nsP2pro with half maximal inhibition concentration (IC50) values of ?34 ?M and ?42 ?M, respectively. Kinetic studies showed that the inhibition constant (Ki) value is 33.34 ± 2.53 ?M for Pep-I and 45.89 ± 4.38 ?M for Pep-II. Additionally, these two compounds significantly inhibited CHIKV replication in BHK-21 cells at concentrations much lower than their cytotoxic concentrations. Intriguingly, these compounds did not show inhibitory effect on Sindbis virus. This suggests that Pep-I and Pep-II compounds identified as CHIKV nsP2 substrate peptidomimetics, specifically inhibit CHIKV replication. © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)
Citation: Biochimie(2018), 149(): 51-61
Issue Date: 2018
Publisher: Elsevier B.V.
Keywords: Antiviral assay
Chikungunya virus
CHIKV-Specific inhibitor
FRET assay
nsP2 protease
Peptidomimetic compounds
Protease inhibitor
ISSN: 3009084
Author Scopus IDs: 57204276008
Author Affiliations: Singh, H., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India,
Mudgal, R., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India,
Narwal, M., De
Funding Details: This work was supported by Department of Biotechnology (DBT), Government of India (Grant ref. number BT/PR9670/MED/29/807/2013 ). HS and VS thank the Ministry of Human Resource Development (MHRD) Govt. of India. RM thanks Council of Scientific and Industr
Corresponding Author: Tomar, S.; Department of Biotechnology, Indian Institute of Technology RoorkeeIndia; email:
Appears in Collections:Journal Publications [BT]

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