Abstract
Background: The COVID-19 pandemic has necessitated an urgent search for effective therapeutics. Protease inhibitors have gained considerable attention as potential antiviral agents against SARS-CoV-2. This literature review aims to evaluate the current state of research on the antiviral activity of protease inhibitors against SARS-CoV-2, focusing on their mechanism of action, in-vitro efficacy, clinical trial findings, and issues related to drug resistance and side effects. Methods: A comprehensive search was conducted across multiple databases, including PubMed, Scopus, and Google Scholar, using relevant keywords. A total of 22 studies, comprising various research designs, were included in the review. Results: Protease inhibitors effectively target key viral enzymes, demonstrating strong binding affinities. In-vitro studies generally indicate a broad-spectrum efficacy against SARS-CoV-2. However, clinical trials have shown mixed results, with some studies indicating significant benefits, while others do not. Side effects are common but generally manageable. The likelihood of drug resistance remains relatively low but is a potential concern. Conclusion: Protease inhibitors hold promise as antiviral agents against SARS-CoV-2 due to their robust mechanisms of action and in-vitro efficacy. However, clinical utility remains a matter of ongoing debate. Further research, particularly longterm and multi-center trials, are essential to fully establish the role of protease inhibitors in COVID-19 treatment. Issues related to drug resistance and side effects need to be carefully considered. Overall, protease inhibitors could serve as a valuable component of a multi-pronged therapeutic approach against COVID-19.