The seminar will be held in MJIS 1001 and live streamed via Zoom (https://purdue-edu.zoom.us/meeting/register/tJUtd-2rrTIqEt28s1D20iZPi-9RRDGj76V5)

Coronaviruses (CoVs) are single-stranded, positive-sense RNA viruses in the Coronaviridae family. Within this family are four genera: Alpha coronavirus, Beta coronavirus, Gamma coronavirus, and Delta coronavirus, with Alpha- and Beta- containing coronaviruses that infect humans and animals. Coronaviruses encode two essential proteases, the papain-like protease (PLP) and the 3C-like protease. PLPs are cysteine proteases that are involved in polyprotein processing of three nonstructural proteins encoded in the virus, and also are involved in evading the innate immune response by having deubiquitinating (DUB) and delSGylating activity. The DUB and delSGylating activity allow PLP to "cloak" the virus, making viral proteins invisible to the host cell. In all, PLPs activities of invisibility, ability to resurrect non-structural protein activity, along with the infectious and deadly nature of some human CoVs, gives it all the qualities that famous author, J.K. Rowling has noted as the "deathly hallows." In our study, we investigate these activities by studying the catalytic function and substrate specificity of multiple PLPs from both Alpha- and Beta-CoVs. Our x-ray structural data of PLPs assist us in understanding these differences in catalytic function. We then probed the active sites of these PLPs using a series of small-molecule inhibitors we designed. These inhibitors ahe shown lower micromolar IC50s against Beta-CoV PLPs like SARS-CoV-2 and SARS-CoV and begin to show inhibition against Alpha-CoV, NL63 PLP2. To strip PLP of being the "Master of Death," we have stolen its ability to process th epolyprotein using developed, small-molecule inhibitors and have begun to unveil its ability in evading the host-innate immune system, arguably making us some of the greatest wizards of all time.

This seminar is sponsored by the Molecular Biophysics Training Program (MBTP) and Structural and Computational Biology and Biophysics (SCCB).