Inhibition of Chikungunya virus by an Adenosine Analog targeting the SAM ‐dependent nsP1 methyltransferase

AbstractAlphaviruses, including Chikungunya (CHIKV) and Venezuelan equine encephalitis virus (VEEV), are among the leading causes of recurrent epidemics all over the world. Alphaviral non ‐structural 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 evaluatedin vitro using a combination of cell ‐based assays, which suggest that 5‐IT is efficacious against CHIKV in cell culture (EC50: 0. 409 µM).

Source: FEBS Letters - October 16, 2019 Category: Biochemistry Authors: Rajat Mudgal, Supreeti Mahajan, Shailly Tomar Tags: RESEARCH ARTICLES Source Type: research