AUTHOR=Al-Karmalawy Ahmed A. , Dahab Mohammed A. , Metwaly Ahmed M. , Elhady Sameh S. , Elkaeed Eslam B. , Eissa Ibrahim H. , Darwish Khaled M. 

TITLE=Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.661230

DOI=10.3389/fchem.2021.661230

ISSN=2296-2646

ABSTRACT=The rapid and global spread of COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for treatment. Here, we consider drug repurposing as an attractive approach that can facilitate the drug discovery process through repurposing of some approved human angiotensin-converting enzyme inhibitors (hACEIs) using various in silico studies. Among 14 examined ACEIs, alacepril and lisinopril interacted with human angiotensin-converting enzyme 2 (hACE2), the host entrance way for SARS-CoV-2 spike protein  and exhibited the most acceptable rmsd_refine values and the best binding affinities through forming a strong hydrogen bond with Asn90 which is assumed to be an essential amino acid for the activity, as well as significant extra interactions with other receptor-binding residues. Furthermore, molecular dynamics (MD) simulations followed by calculating the binding free energies were also carried out for the most promising two ligand-pocket complexes from docking studies (alacepril and lisinopril) to clarify some information on their thermodynamic and dynamic properties and confirm the docking results as well. The obtained results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiments and accurate clinical trials are needed to confirm the potential preventive and treatment effect of these compounds.