Fighting COVID19 with calpain inhibitors / Consortium: Calpain-antivirals

It is important to develop coronavirus (CoV) targeting antivirals as it remains unclear if and when a safe and efficient vaccine becomes available. We propose to create antivirals against CoV proteases that process the virus polyprotein to virus capsid proteins by using a novel approach, by inhibiting cellular calpain enzymes. We have preliminary results showing that calpain inhibitors prevent COVID19 infection. In addition, we have shown that calpain inhibitors knock down both host cell calpains and the enteroviral protease, that both contribute to virus polyprotein processing. We reckon that calpain inhibitors attack both host cell calpain proteases and viral 3C-like protease, closely resembling enterovirus 3C protease, and both process the viral polyprotein. In the project we will find the inhibitor with best efficacy, chemically optimize the inhibitor with new design, synthesis and efficacy against virus infection.