Computational modeling and inhibition of SARS-COV-2 Papain-like protease enzyme: A potential therapeutic approach for COVID-19

Abstract

This study aims to investigate the potential impact of inhibitors targeting the papain-like protease (PLpro) of SARS-CoV-2 on viral replication and the host immune response. A mathematical model was developed to simulate the interaction among susceptible cells, infected cells, PLpro, and immune cells, incorporating data on PLpro inhibition. Through numerical simulations using MATLAB, the model parameters were estimated based on available statistical data. The results indicate that strategically positioned inhibitors could impede the virus’s access to host cellular machinery, thereby enhancing the immune response and gradually reducing susceptible and infected cells over time. The dynamics of the viral enzyme PLpro showed reduced activity with the introduction of the inhibitor, leading to a decline in viral replication. Moreover, the immune cell population exhibited functional recovery as the inhibitor suppressed PLpro activity. These findings suggest that inhibitors targeting PLpro may serve as therapeutic interventions against SARS-CoV-2 by inhibiting viral replication and bolstering the immune response.

Keywords

• COVID-19
• Viral replication
• Papain-like protease (PLpro)
• Mathematical modeling
• Noncovalent inhibitors
• Immune response