Venom Peptides of Crotalus atrox Against SARS-Cov-2 Spike Protein and Human ACE2 Receptor by Molecular Docking Analysis

Abstract

Venoms are composed of about 100 to 500 pharmacologically active compounds. Less than 0.01% of these compounds have been identified and a significant majority of them act on unknown receptors. Here, the potential Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) activities of selected Crotalus atrox venom peptides (CVPs) including Atrolysin D (AD), vascular apoptosis-inducing protein-1 (VAIP-1), Catrocollastatin (CC), and Calcium-Free Phospholipase A2 (CFP) were investigated via molecular docking analysis. CVPs were docked against human angiotensin-converting enzyme-2 (ACE-2) and 3-chymotrypsin-like protease (3CLpro) viral spike protein. All CVPs had low binding energies to both 3CLpro and ACE2, suggesting that they interacted strongly with the active sites of enzymes, compared to the reference drugs lopinavir and ritonavir. The binding energy of 3CLpro was -139.517 kcal/mol, -96.239 kcal/mol, -121.590 kcal/mol, -259.424 kcal/mol with AD, VAIP-1, CC, and CFP, respectively. CFP showed a very strong binding activity with 3CLpro, suggesting that it could be a very effective compound in inhibiting the SARS-CoV-2 virus. The binding energy of ACE2 was -101.165 kcal/mol, -73.064 kcal/mol, -106.918 kcal/mol, -82.830 kcal/mol with AD, VAIP-1, CC, and CFP, respectively. AD made a much stronger bond with ACE2 than reference drugs, showing that it could be used as a virus-protective component in humans. The results suggest a potential drug candidate for the development of therapeutics against Coronavirus disease 2019 (COVID-19). In vitro and in vivo experiments are needed to confirm these compounds' potential preventive and therapeutic effects.