Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) enters the cell by interacting with the human angiotensin-converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of spike (S) protein. In the cell, the viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme is essential for its life cycle and controls coronavirus replication. Therefore, the S-RBD and 3CLpro are hot targets for drug discovery against SARS-CoV-2. This study was to identify repurposing drugs using in silico screening, docking, and molecular dynamics simulation. The study identified bentiamine, folic acid, benfotiamine, and vitamin B12 against the RBD of S protein and bentiamine, folic acid, fursultiamine, and riboflavin to 3CLpro. The strong and stable binding of these safe and cheap vitamins at the important residues (R403, K417, Y449, Y453, N501, and Y505) in the S-protein-ACE2 interface and 3CLpro binding site residues especially active site residues (His 41 and Cys 145), indicating that they could be valuable repurpose drugs for inhibiting SARS-CoV-2 entry into the host and replication.
Keywords: Coronavirus; Docking; Drug discovery; Main protease; Molecular dynamics; Receptor-binding domain.
【저자키워드】 coronavirus, Drug discovery, main protease, docking, molecular dynamics, receptor-binding domain., 【초록키워드】 SARS-CoV-2, ACE2, Drug discovery, S protein, drug, 3CLpro, docking, molecular dynamics, in silico, severe acute respiratory syndrome Coronavirus, vitamins, binding site, Molecular dynamics simulation, Folic acid, Replication, Protein, Receptor-binding domain, RBD, S-RBD, Control, target, Vitamin, receptor, binding, S-protein, angiotensin, Coronavirus replication, Riboflavin, Safe, life cycle, cysteine, active site, vitamin B12, acute respiratory syndrome, acute respiratory syndrome coronavirus, enzyme, SARS-CoV-2 entry, residue, cysteine protease, human Angiotensin-converting enzyme, K417, Y449, Host, Cell, benfotiamine, fursultiamine, R403, identify, the RBD, the receptor-binding domain, inhibiting, 【제목키워드】 COVID-19, molecular docking, repurposing, protease, Spike protein, Compound, potential therapeutic agent, the receptor-binding domain,