Eventually, animal experiments and accurate clinical trials are needed to confirm the potential preventive and treatment effect of these compounds. These results we obtained probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Furthermore, molecular dynamics (MD) simulations followed by calculation of the binding free energy 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. Alacepril and lisinopril were found to interact with human angiotensin-converting enzyme 2 ( hACE2), the host entranceway for SARS-CoV-2 spike protein, through exhibiting the most acceptable rmsd_refine values and the best binding affinity through forming a strong hydrogen bond with Asn90, which is assumed to be essential for the activity, as well as significant extra interactions with other receptor-binding residues.

Besides, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2. We review current information concerning the global health issue of COVID-19 including promising approved drugs, e.g., human angiotensin-converting enzyme inhibitors ( hACEIs). Here, we consider drug repurposing as an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. The rapid and global spread of a new human coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19.

7Department of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.

6Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.

5Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia.

4Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

3Pharmacognosy Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.

2Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.

1Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, Damietta, Egypt.

Microsoft office activation wizard nag