VBY-825 is a reversible cysteine protease inhibitor with high potency against cathepsins B, L, S and V [1
]. Human cysteinyl cathepsins are required for proteolytic processing of virally encoded proteins during infection [2-3
], including a likely requirement for proper processing of the SARS-CoV-2 S protein within the endosome (activating its fusogenic acitivity) [5
]. Experimental evidence indicates that VBY-825 has some antiviral activity against SARS-CoV-2 [4
]. In in vitro
experiments VBY-825 inhibits SARS-CoV-2 entry. It does not inhibit the viral 3C-like protease (3CLpro) or papain-like protease (PLpro), which suggests that its antiviral activity is associated with inhibition of host proteases.
In the oncology setting, a pre-clinical model of pancreatic islet cancer revealed that VBY-825 exhibits significant anti-tumour activity.