Muhammad Rahat- UMass Fellow 2024-2025
Research Progress: I am doing my Ph.D. in Dr. Jeanne Hardy's lab in the chemistry department. I am working on a very exciting project for the development of antivirals for the Chikungunya Virus. Chikungunya infection is transmitted through mosquitoes and has infected over 3 million people. This infection induces symptoms of high fever, rashes, joint swelling and
infection at a late stage of pregnancy, which can cause encephalopathy in newborns. To date, there is no anti-viral for the infection, and there is a pressing need for one. During its life cycle, nsP2 protease plays a vital role in the maturation of polyproteins, and it is
an excellent therapeutic target for controlling the disease. Our approach has identified small-molecule binder F2526-0071 for CHIKV protease nsP2 (CHIKVP) through NMR screening. These binders interact with the methyltransferase (Mtase) domain of nsP2, as confirmed by chemical shift perturbation (CSP) in NMR experiments. Initial inhibition assays showed weak activity (IC₅₀ = 5.400 mM, Kd = 850 µM). Structure-activity relationship (SAR) studies have led to the synthesis of analogues MAR-01 through MAR-11, which are characterised by analytical
techniques like NMR and improving efficacy by six-fold, IC₅₀ of 0.862 mM for MAR-09. In the last year, I have been able to develop an assay to measure the Kd using microscale thermophoresis, which proved to be a more time- and cost-effective approach.