In Silico Antiviral Drug Repurposing Against COVID-19 Infection: Targeting the Main Protease and Human ACE2 Receptor

Coronavirus Disease-2019 (COVID-19) is a highly contagious respiratory illness caused by a novel coronavirus known as SARS-CoV-2. The virus exerts its pathogenic activity and infects new cells by utilizing the spike protein (S1) of the coronavirus and the Angiotensin-converting enzyme 2 (ACE2) receptor protein found in host cells, thereby transferring the genetic material. The SARS-CoV-2 main protease, essential for viral replication, presents a promising therapeutic target due to its structural and sequence similarity with other beta coronaviruses, facilitating drug development from existing lead compounds. With this context, we have considered SARS-CoV-2 Main protease and spike protein combined with ACE2 receptor as the target protein for inhibiting the replication. In this study, we employed High-Throughput Virtual Screening (HTVS) to screen antiviral compounds from the drug bank. Based on the docking score, two compounds were screened with respect to the selected target proteins. Subsequently, Molecular docking investigations were conducted for compound A and compound B concerning the main protease and ACE2 receptor, which yields favorable docking scores of -8.212 kcal/mol and -9.373 kcal/mol, respectively. Further molecular dynamics, DFT studies and ADMET parameters were carried out to understand the stability, reactivity, and toxicity profile of the screened compounds. This work focus on finding the potential antiviral lead compounds to combat SARS-CoV2 using computational methods. Utilizing Virtual Screening, Molecular Docking, Molecular Dynamics Simulation, and DFT approaches with main protease and ACE2 receptor, we proposed the optimal COVID-19 inhibitor by analyzing its ADMET properties.image