Molecular dynamic simulation reveals spider antimicrobial peptide Latarcin-1 and human eosinophil cationic protein as peptide inhibitors of SARS-CoV-2 variants

• Published in: Journal of biomolecular structure & dynamics Vol. 42; no. 11; pp. 5858 - 5868
• Main Authors: Cao, Cheng, Mehmood, Aamir, Li, Daixi
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 23.07.2024
• Subjects: ACE2; Angiotensin-Converting Enzyme 2 - chemistry; Angiotensin-Converting Enzyme 2 - metabolism; Animals; Antimicrobial Peptides - chemistry; Antimicrobial Peptides - pharmacology; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Arthropod Proteins - chemistry; Binding Sites; COVID-19 - virology; COVID-19 Drug Treatment; Eosinophil Cationic Protein - chemistry; Eosinophil Cationic Protein - metabolism; Humans; Molecular Docking Simulation; molecular dynamics; Molecular Dynamics Simulation; peptide inhibitors; Protein Binding; SARS-CoV-2; SARS-CoV-2 - drug effects; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - metabolism; variants; peptide inhibitors; ACE2; SARS-CoV-2; variants; molecular dynamics
• ISSN: 0739-1102; 1538-0254; 1538-0254
• DOI: 10.1080/07391102.2023.2274514

COVID-19 has rapidly proliferated around 180 countries, and new cases are reported frequently. No peptide medication has been developed that can reliably block SARS-CoV-2 infection. The investigation focuses on the crucial host receptors angiotensin-converting enzyme 2 (ACE2) , which can bind receptor-binding domain (RBD) on the SARS-CoV-2 spike protein (S). To investigate the inhibitory effects of human Eosinophil Cationic Protein (hECP) and Latarcin-1 (L1)on SARS-CoV-2 infection, we have selected them as research subjects. Further, we ran extensive molecular dynamics simulations to bring the docked peptide-ACE2 complex into its equilibrium state. The outcomes were then evaluated with g_MMPBSA and interaction analysis. We have also considered the Delta and Omicron variants to examine these peptides' inhibitory effects. The experimental findings revealed an enhanced capability of L1 and hECP as SARS-CoV-2 inhibitors, occupying hot spots and numerous key residues in ACE2. These include ASP30, ASP38, GLU35 and GLU75, which significantly inhibit the binding of RBD and ACE2 and are effective against two common variants in a similar manner. In addition, this study can serve as a springboard for future research on SARS-CoV-2 inhibitors. Communicated by Ramaswamy H. Sarma