Picornaviral 3C protease inhibitors and the dual 3C protease/coronaviral 3C-like protease inhibitors

Abstract

Importance of the field: Picornaviruses are small non-enveloped RNA viruses with genomic RNA of 7500 – 8000 nucleotides, whereas coronaviruses (CoV) are RNA viruses with larger genome of 27 – 32 kb. Both types of viruses translate their genetic information into polyprotein precursors that are processed by virally encoded 3C proteases (3C^pro) and 3C-like proteases (3CL^pro), respectively, to generate functional viral proteins. The most studied human rhinoviruses (HRV) belonging to picornaviridae family are the main etiologic agents of the common cold. Due to lack of effective drugs, 3C^pro has served as an excellent target for anti-viral intervention and considerable efforts have been made in the development of inhibitors. Interestingly, the inhibitors of 3C^pro cannot inhibit 3CL^pro potently without modification due to subtle differences in their active-site structures, but a group of common inhibitors against 3C^pro and 3CL^pro were found recently.

Areas covered in this review: The inhibitors against 3C^pro reported in the literatures and patents, with a focus on those inhibiting HRV and the dual picornaviral 3C^pro/coronaviral 3CL^pro inhibitors, are summarized in this review.

What the readers will gain: Readers will rapidly gain an overview of the individual and dual 3C^pro inhibitors and the structural basis for discriminating them.

Take home message: In the future, more selective potent inhibitors against each protease and dual inhibitors against both proteases can be further developed to treat the diseases caused by picornaviruses and CoV.

Keywords::

• 3C protease
• 3CL protease
• coronavirus
• inhibitor
• picornavirus
• rhinovirus

Acknowledgement

Both authors contributed equally to the preparation of this review.