CONFORMATIONAL FLEXIBILITY IS A CRITICAL FACTOR IN DESIGNING BROAD-SPECTRUM HUMAN NOROVIRUS PROTEASE INHIBITORS.

ABSTRACT: Human norovirus (HuNoV) infection is a global health and economic burden. Currently, there are no licensed HuNoV vaccines or antiviral drugs available. The protease encoded by the HuNoV genome plays a critical role in virus replication by cleaving the polyprotein and is, therefore, an excellent target for developing small molecule inhibitors. While rupintrivir, a potent small-molecule inhibitor of several picornavirus proteases, effectively inhibits GI.1 protease, it is an order of magnitude less effective against GII protease. Other GI.1 protease inhibitors also tend to be less effective against GII proteases. To understand the structural basis for the potency difference, we determined the crystal structures of proteases of GI.1, pandemic GII.4 (Houston and Sydney), and GII.3 in complex w

SUBMITTER: Pham S 

PROVIDER: S-EPMC11430002 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature