Functional Analysis of Mouse Hepatitis Virus protease nsp5 Interdomain Loop

Megan Franke Butler University, Mansi Pandya Butler University, Sean Callahan Butler University, Emily Hasik Butler University, Benjamin Nick Butler University, Christopher Stobart Butler University
Faculty Sponsor(s): Christopher Stobart Butler University
Human coronaviruses cause the common cold as well as other more lethal respiratory diseases such as severe acute respiratory syndrome (SARS). Nsp5 is an essential protease for coronavirus replication and is a major target of current coronavirus inhibitor design efforts. Mouse hepatitis virus (MHV) is the primary model organism to study the biology of coronaviruses. Nsp5 is a 3-domain protease with a unique interdomain loop (IDL) connecting domains 2 and 3 of unknown function. A panel of mutants containing point mutations in conserved regions within the IDL have been generated via site-directed mutagenesis. These mutants were evaluated for debilitated growth under ideal conditions, tested for increased temperature sensitivity, and evaluated for the emergence of additional mutations to increase stability. In addition to several mutations which were lethal to virus replication, several other mutations identified new vital amino acid residues within the IDL. These studies provide the first insight into this structure of the coronavirus nsp5 protease and may represent new targets for inhibitor design.
Biochemistry & Molecular Biology
Oral Presentation

When & Where

10:30 AM
Gallahue Hall 108