Background: Noroviruses are the leading cause of acute gastroenteritis
worldwide. Norovirus proteases, which are responsible for cleavage of the viral polyprotein,
have become an attractive drug target to treat norovirus infections.
Genogroup II (GII) noroviruses are responsible for a majority of outbreaks; however,
limited data exists regarding GII norovirus proteases.
Methods: We report here successful expression, purification, characterization, and inhibition
of the Minerva virus protease (MVpro), a genogroup II genotype 4 (GII.4) norovirus
protease. We observed MVpro as both a monomer and dimer in solution through sizeexclusion
chromatography. In addition, MVpro cleaves the synthetic substrate mimicking
the MVpro NS2/NS3 cleavage site more efficiently than other norovirus proteases such as
the Norwalk virus protease (GI.1) and the MD145 protease (GII.4).
Results and Conclusion: Compound A, a potent inhibitor of MVpro, is a good starting
point for the design of inhibitors to target GII.4 noroviruses. Furthermore, the results
presented here will allow for future characterization of MVpro inhibitors as
they are synthesized.