Therapeutic Intervention Strategies of SARS-CoV-2
January 30, 2021
Presented by Joyce Jose
Assistant Professor, Department of Biochemistry and Molecular Biology
The ongoing COVID-19 pandemic is underscoring the urgent need to develop effective antiviral agents for SARS-CoV-2, the causative agent of COVID-19. The rapid identification of effective interventions against SARS-CoV-2 has been proven to be a significant challenge. The SARS-CoV-2 proteases Mpro and PLpro that cleave the viral polyproteins are excellent antiviral targets to prevent SARS-CoV-2 replication. Based on the success of protease inhibitors against HIV and the proven efficacy of protease inhibitors against related members in the Coronaviridae family, we are developing protease inhibitors as antiviral agents to tackle COVID-19. My laboratory has established an in-cell protease assay system that allows us to screen hundreds of small-molecule inhibitors and identify compounds that inhibit SARS-CoV-2 replication in human cells tested in the BSL-3 facility. Along with determining the mechanism of protease inhibition by targeting its active site using biochemical and structural biology approaches, our goal is to optimize the inhibitors by synthesizing derivatives with improved on-target biological activity and limited cytotoxicity by an iterative process of computational chemistry, structural biology, and antiviral activity. I will discuss our findings in drug repurposing for SARS-CoV-2, the development of novel viruslike particles as vaccine candidates, and screening SARS-CoV-2 entry inhibitors.
Joyce Jose is an assistant professor in the Department of Biochemistry and Molecular Biology at Penn State. She received her doctorate in biochemistry and molecular biology from the School of Biotechnology at Madurai Kamaraj University, India, and completed her postdoctoral research at Dr. Richard J. Kuhn's laboratory at Purdue University. Jose’s research lab at Penn State works on the replication and assembly of positive-strand RNA viruses, specifically Zika virus, dengue virus, and BSL-3 pathogens including Powassan virus, as well as chikungunya virus and SARS-CoV-2. Her current research on enveloped, positive-strand RNA viruses has three main goals: to determine the virus-host interactions in the pathogenesis of BSL-3 viruses, to understand the mechanism of virus genome assembly and budding, and to develop therapeutic intervention strategies against pathogenic viruses. She uses reverse genetics, molecular virology, live-cell imaging, super-resolution microscopy, and electron microscopy to study various virus-host interactions. The Jose lab has established SARS-CoV-2 research in BSL-3 to understand virus entry and exit mechanisms and develop therapeutic intervention strategies against SARS-CoV-2. Her BSL-3 work on SARS-CoV-2 has been instrumental in providing critical mechanistic insights into virus entry and receptor recognition.