Mansi Pandya Butler University, Megan Franke Butler University, Emily Hasik Butler University, Sean Callahan Butler University, Benjamin Nick Butler University, Christopher Stobart Butler University
Faculty Sponsor(s): Christopher Stobart Butler UniversityCoronaviruses are enveloped, positive-sense single-stranded RNA viruses that are known to infect a wide range of organisms including humans. It is known that infection in humans leads to the common cold and severe acute respiratory syndrome (SARS), thus highlighting a need for effective vaccines and therapeutics. As the virus enters a host, the entire replicase gene of the coronavirus is translated into 2 large polyproteins. Nonstructural protein 5 (nsp5) is a viral protease that is responsible for cleaving the polyprotein at 11 distinct sites and is required for viral replication. Nsp5 structure is characterized by 3 domains with an interdomain loop of unknown function that connects domains 2 and 3. While the interdomain loop is structurally conserved among coronaviruses, it remains unclear how well this loop tolerates genetic changes. We used mouse hepatitis virus (MHV) as a model for coronavirus biology to mutate specific residues in the interdomain loop and analyzed their flexibility and tolerance of the molecular changes. A number of residues demonstrated viral replication defects and were passaged for reversion analysis. These studies provide new insight into the role of the coronavirus nsp5 interdomain loop and its molecular interactions with other parts of the nsp5 protease.
When & Where
Gallahue Hall 106