Medicinal Chemistry and Pharmacology of Antivirals Targeting SARS-CoV-2
My lab is interested in developing antivirals targeting emerging and re-emerging viruses, including influenza A and B viruses, enterovirus D68 (EV-D68), EV-A71, coxsackievirus, poliovirus, and the coronaviruses such as SARS-CoV-2. The central themes are the identification of new drug targets and the development of novel small molecules for use as chemical probes for target validation as well as drug candidates for translational research.
In this talk, I will introduce our efforts in developing antivirals targeting SARS-CoV-2 main protease (Mpro or 3CLpro) and papain-like protease. Mpro and PLPro are involved in the cleavage the viral polyproteins during the viral replication and are validated antiviral drug targets. In addition, PLpro has been shown to modulate host immune response. Through high-throughput screening and structure-based drug design, we have discovered covalent and non-covalent Mpro and PLpro inhibitors with potent enzymatic inhibition and cellular antiviral activity against SARS-CoV-2. In addition, we have solved multiple X-ray co-crystal structures of Mpro and PLpro with inhibitors. The talk will focus on target selectivity, new cysteine reactive warheads, assay development, and pharmacology of Mpro and PLpro inhibitors.
Hosted by Professor Zheng Shi