Enfuvirtide, an HIV-۱ fusion inhibitor peptide, can act as a potent SARS-CoV-۲ fusion inhibitor: an in silico drug repurposing study

Background & objectives: Regarding the urgency of therapeutic measures for coronavirus disease ۲۰۱۹ (COVID-۱۹) pandemic, the use of available drugs with FDA approval is preferred because of the less time and cost required for their development.Based on the most important criteria such as docking score, cluster size, energy and dissociation constant, the strongest interaction was observed between Enf with the S۲ protein. In addition, MD results confirmed that EnfS۲ protein interaction was remarkably stable and caused the S۲ protein residues to undergo the fewest fluctuations. In Conclusions, it can be stated that Enf can act as a strong SARS-CoV-۲ fusion inhibitor and demonstrates the potential to enter the clinical trial phase of COVID-۱۹.Methods and Materials:Receptor and ligand preparation and identifying the binding sitesMolecular dockingMD simulationPMF (potential of mean force)Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methodFindings:Comparison of key residues of binding sites of S۲ and gp۴۱ proteins Analysis of interactions between drug and different protein receptors and evaluation of their binding affinity MD simulation and PMF analysis Conclusions, In the present in silico study, we examined the amino acids involved in the Enf-S۲ protein interaction and compared the binding strength with gp۴۱ HIV and ACE۲ receptor. Also, the stability of this interaction was evaluated by MD simulation with various analyzes. The results showed that Enf has a good interaction with the most important residues of the HR۲ domain of SARS-CoV-۲ S۲ protein and can act as a fusion inhibitor of this virus. Therefore, based on our results and present information about the pharmacological properties of Enfuvirtide, we recommend that this FDA approved antiviral drug has the potential to enter the clinical trial phase for the treatment of the COVID-۱۹.

کلیدواژه ها:

ACE-۲: angiotensin-converting enzyme ۲ ، Enf: Enfuvirtide ، HIV ، human immunodeficiency virus