Authors:

Misa Meadows

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About Paper:

The effects of the Covid-19 global pandemic caused by the betacoronavirus, SARS-CoV-2, has emphasized the importance of studying newly emerging coronaviruses that could potentially cause further pandemics. The recent emergence of CCoV-HuPn-2018 (CCoV), a human-infecting canine coronavirus, was detected in patients with pneumonia in Malaysia, identifying CCoV as a zoonotic virus. Upon sequencing, the novel CCoV was classified as an alphacoronavirus, similar to other animal-infecting coronaviruses such as the feline infectious peritonitis virus (FIPV), which infects cats. Coronaviruses are single-stranded positive RNA viruses that translate their genome into two large polypeptides, pp1a and pp1ab. The 3-Chymotrypsin-like protease (3CLpro) is responsible for cleaving these polypeptides at eleven sites to form smaller, non-structural proteins that are essential for viral replication. The importance of the 3CLpro and its conservation amongst various coronaviral genera make it an attractive drug target. The objective of our study is to repurpose small molecule inhibitors designed against SARS-CoV-2 in efforts to establish broad-spectrum inhibition against alphacoronaviruses CCoV and FIPV. In this study, we use a fluorescent-based peptidomimetic substrate to characterize and compare the 3CLpro enzymatic properties. We further performed Structure Activity Relationship (SAR) studies to identify characteristics of the inhibitors contributing to broad-spectrum efficacy. To understand how the identified inhibitors affect the stability of the protein, the melting temperatures of the 3CLpros bound to these inhibitors were quantified using Differential Scanning Fluorimetry (DSF). Together, this study provides valuable information for the future development of broad spectrum inhibitors against various coronaviral genera.

Source:

Purdue University / 2023

Topics:

No topics listed

Co-authors:

Misa Meadows