In silico antiviral effect assessment of some venom gland peptides from Odontobuthus doriae scorpion against SARS-CoV-2.

SARS-CoV-2 is from the enveloped virus family responsible for the COVID-19 pandemic. No efficient drugs are currently available to treat infection explicitly caused by this virus. Therefore, searching for effective treatments for severe illness caused by SARS-CoV-2 is crucial. Scorpion venoms are significant sources of peptides with pharmaceutical potential, including antivirals. Although some studies have determined the antiviral effects of some scorpion peptides on other members of the Coronaviridae family, a few anti-SARS-CoV-2 effects of these peptides have been reported until now. This study assessed the antiviral effects of five predicted antimicrobial peptides with potential for antiviral activities from the Iranian yellow scorpion "Odontobuthus doriae" by computational methods. These peptides were selected from the cDNA library that our research team constructed. A 3D model of peptides was designed with I-TASSER. The models were refined using a 200 ns Molecular Dynamics (MD) simulation using Gromacs 2021.2 software. Refined models were Docked with the RBD domain of SARS-CoV-2 spike protein using HADDOCK software. The docking of human ACE2 peptide with the RBD domain was also assessed. The docked complexes (RBD-peptide and RBD-ACE2) were refined again by a 100 ns MD simulation and then analyzed. The results from molecular docking after molecular dynamics simulation showed that ODAMP2 and ODAMP5 after stabilizing analysis and according to MMPBSA results (with -59.24 kcal/mol and -51.82 kcal/mol, respectively) have a strong binding affinity to the RBD domain of COVID-19 spike protein compared to human ACE2 and some other studied components. Therefore, this peptide can be an excellent candidate for use as an agent to inhibit the RBD domain of SARS-COV2 virus in clinical studies for medicinal purposes after in vitro and in vivo laboratory evaluations.