Development of superior antibodies against the S-protein of SARS-Cov-2 using macrocyclic epitopes

Hassan Traboulsi; Mohammed A Khedr; Rafea Elgorashe; Yasair Al-Faiyz; Amr Negm

doi:10.1016/j.arabjc.2021.103631

Development of superior antibodies against the S-protein of SARS-Cov-2 using macrocyclic epitopes

Arab J Chem. 2022 Mar;15(3):103631. doi: 10.1016/j.arabjc.2021.103631. Epub 2021 Dec 10.

Authors

Hassan Traboulsi¹, Mohammed A Khedr^{2

3}, Rafea Elgorashe¹, Yasair Al-Faiyz¹, Amr Negm^{1

4}

Affiliations

¹ Department of Chemistry, College of Science, King Faisal University, P.O Box 400, Al-Ahsa 31982, Saudi Arabia.
² Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-AHasa 31982, Saudi Arabia.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, P.O. Box 11795, Cairo, Egypt.
⁴ Biochemistry Division, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt.

Abstract

One of the proven methods to prevent and inhibit viral infections is to use antibodies to block the initial Receptor Binding Domain (RBD) of SARS-CoV-2 S protein and avoid its binding with the host cells. Thus, developing these RBD-targeting antibodies would be a promising approach for treating the SARS-CoV-2 infectious disease and stop virus replication. Macrocyclic epitopes constitute closer mimics of the receptor's actual topology and, as such, are expected to be superior epitopes for antibody generation. This work demonstrated the vital effect of the three-dimensional shape of epitopes on the developed antibodies' activity against RBD protein of SARS-CoV-2. The molecular dynamics studies showed the greater stability of the cyclic epitopes in comparison with the linear counterpart, which was reflected in the activity of their produced antibodies. Indeed, the antibodies we developed using macrocyclic epitopes showed superiority with respect to binding to RBD proteins compared to antibodies formed from a linear peptide. The results of the present work constitute a roadmap for developing superior antibodies that could be used to inhibit the activity of the SARS-CoV-2 and prevent its reproduction.

Keywords: Antibodies; Epitopes; Inhibition; Macrocyclic peptides; Molecular dynamics; Receptor binding domain; SARS-CoV-2; Spike protein.