Viral proteases as targets for antivirals drugs

The biochemical machinery of all viruses comprises enzymes able to cleave polyproteins formed after the transcription of the viral genetic material, which belong to the protease class. Viral proteases known so far belong to the aspartic, serine and cysteine protease classes, with no viral metalloprotease described to date. The tridimensional structure, biochemical properties and susceptibility to be inhibited by various classes of compounds for many such enzymes have been investigated in detail in the last decades. Many antiviral drugs target viral proteases which produce diseases in mammals, but such enzymes are also present in viruses which attack plants or bacteria, and potential applications for such enzymes or their inhibition started to be considered in recent years. The aspartic protease encoded in the HIV genome, the serine proteases found in various HCV serotypes and more recently the two cystein proteases from coronaviruses, including SARS CoV 2, are targeted by clinically used drugs belonging to the protease inhibitors, which effectively interrupt the life cycle of the virus, alone or in combination therapies with other antivirals and showed a relevant clinical success. Many other less investigated viruses encode for proteases belonging to the three classes mentioned above and they started to be investigated for obtaining novel antivirals for the management of Dengue, Zika, West Nile and other flaviviruses infections but also Chikungunya, Ebola, Marbug and various other filoviruses, for which few therapeutic options are available to date.