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. 2020 Dec 28:61:122-125.
doi: 10.1016/j.amsu.2020.12.030. eCollection 2021 Jan.

Protease inhibitor GC376 for COVID-19: Lessons learned from feline infectious peritonitis

Khan Sharun  1 , Ruchi Tiwari  2 , Kuldeep Dhama  3
Affiliations

Protease inhibitor GC376 for COVID-19: Lessons learned from feline infectious peritonitis

Khan Sharun et al. Ann Med Surg (Lond). .

Abstract

The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important therapeutic target as it plays a major role in the processing and maturation of the viral polyprotein. GC376 is a pre-clinical dipeptide-based protease inhibitor that has been previously used for managing feline infectious peritonitis virus (FIPV). Since both GC373 and GC376 have already been successfully used in treating animal coronavirus infection, they can be considered as strong drug candidates for COVID-19 in humans. GC376 is a broad-spectrum antiviral drug that inhibits Mpro of several viruses, including the coronaviruses like feline coronavirus, porcine epidemic diarrhoea virus, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, ferret, and mink coronavirus. However, further studies should be conducted to evaluate the potency, efficacy, and safety of these broad-spectrum Mpro inhibitors in patients with COVID-19. The lessons learned from the successful use of drug candidates for treating animal coronavirus infections will help us to develop framework for their use in human trials.

Keywords: COVID-19; Feline coronavirus; Feline infectious peritonitis; Main protease inhibitor; SARS-CoV-2; Therapeutics.

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Conflict of interest statement

All authors declare that there exist no commercial or financial relationships that could, in any way, lead to a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Neurological FIP in a cat with CNS involvement presented with neurological deficits that was treated with GS-441524. Reproduced from Dickinson (2020) Creative Commons Attribution License (CC BY). A–D: pre-contrast, pre-treatment MRI sequences. E–H: post-contrast T1-weighted and fluid-attenuated inversion recovery MRI sequences showing multifocal leptomeningeal lesions (arrowheads). I–L: treatment with GS-441524 (10 mg/kg) resulted in resolution of clinical signs and MR lesions on images acquired 7.5 months after initiation of treatment. (T1 - T1-weighted, FL - fluid-attenuated inversion recovery, +C - using contrast: gadopentetate dimeglumine).
Fig. 2
Fig. 2
Therapeutic candidates that can inhibit the replication of SARS-CoV-2 by inhibiting the main protease (Mpro) (also called as 3CLpro) and RdRp.
See this image and copyright information in PMC

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