Diversity in Life Sciences

Development of NLRP3 inflammasome inhibitors: Aberrant activation of the innate immune system forms the pathophysiological basis of a variety of disorders, including Alzheimer’s, Parkinson’s, multiple sclerosis, life-threatening pathogenic infections, and sickle cell disease. NLRP3 inflammasome is a key component of the innate immune system, and has emerged as a druggable target for the treatment of neurocognitive, neuropsychiatric, and other immune-associated disease states. Guided by computational chemistry, we are developing novel, natural product-inspired platforms with NLRP3 inhibitory activity. Our compounds have shown good in vitro activity against inflammation triggered by a potential bioterror agent, Fracisella tularensis and against LPS-induced neuroinflammation in vitro and in vivo. Current research is focused on pharmacophore refinement leading to analogues with improved activity and penetration into the blood-brain barrier.

Development of antiviral compounds: Our research is focused on the development of small molecule inhibitors of Ebola and Marburg virus. Particularly, we are designing inhibitors of protein phosphatase 1, a host enzyme critical for viral replication. Using a combination of computational and classical drug design approaches, we have developed a library of compounds with good antiviral activity, plasma stability, and low toxicity.

Therapeutics targeting HIV-comorbidities and cure: HIV-protein Nef plays a critical role in HIV pathogenicity and co-morbidities, such as, dyslipidemia and neurocognitive dysfunction. Nef binds to endoplasmic reticulum chaperone, calnexin. Our research is focused on the development of compounds that disrupt the Nef-calnexin interaction. These agents suppressed HIV-replication in vitro. Current studies are focused on screening the application of our compounds in HIV comorbidities in vivo.