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Title: Inhibition of Chikungunya virus by an adenosine analog targeting the SAM-dependent nsP1 methyltransferase
Authors: Mudgal R.
Mahajan S.
Tomar, Shailly
Published in: FEBS Letters
Abstract: Alphaviruses, including Chikungunya (CHIKV) and Venezuelan equine encephalitis virus (VEEV), are among the leading causes of recurrent epidemics all over the world. Alphaviral nonstructural protein 1 (nsP1) orchestrates the capping of nascent viral RNA via its S-adenosyl methionine-dependent N-7-methyltransferase (MTase) and guanylyltransferase activities. Here, we developed and validated a novel capillary electrophoresis (CE)-based assay for measuring the MTase activity of purified VEEV and CHIKV nsP1. We employed the assay to assess the MTase inhibition efficiency of a few adenosine analogs and identified 5-iodotubercidin (5-IT) as an inhibitor of nsP1. The antiviral potency of 5-IT was evaluated in vitro using a combination of cell-based assays, which suggest that 5-IT is efficacious against CHIKV in cell culture (EC50: 0.409 µm). © 2019 Federation of European Biochemical Societies
Citation: FEBS Letters(2020), 594(4): 678-694
Issue Date: 2020
Publisher: Wiley Blackwell
Keywords: adenosine analog
alphavirus inhibitor
CE-based MTase assay
Chikungunya virus
ISSN: 145793
Author Scopus IDs: 57195322398
Author Affiliations: Mudgal, R., Department of Biotechnology, Indian Institute of Technology Roorkee, India
Mahajan, S., Department of Biotechnology, Indian Institute of Technology Roorkee, India
Tomar, S., Department of Biotechnology, Indian Institute of Technology Roorkee, India
Funding Details: This work was supported by Science and Engineering Research Board, Department of Science and Technology, Government of India (EMR/2016/004938). RM is thankful to CSIR, and SM is thankful to MHRD for financial support. Authors are indebted to Andrew S Miller at Purdue University, US, for his help in MALDI?TOF experiments. Authors would also like to acknowledge Mr. Ravi Kumar Marikanty, Mr. Jagmohan Singh, and Mr. Nitin Vig from Agilent Technologies, India, for technical assistance in CE analysis. The funders played no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.
Corresponding Author: Tomar, S.; Department of Biotechnology, Indian Institute of Technology RoorkeeIndia; email:
Appears in Collections:Journal Publications [BT]

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