Traboulsi Hassan, Khedr Mohammed A, Elgorashe Rafea, Al-Faiyz Yasair, Negm Amr
Department of Chemistry, College of Science, King Faisal University, P.O Box 400, Al-Ahsa 31982, Saudi Arabia.
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-AHasa 31982, Saudi Arabia.
Arab J Chem. 2022 Mar;15(3):103631. doi: 10.1016/j.arabjc.2021.103631. Epub 2021 Dec 10.
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.
预防和抑制病毒感染的一种已被证实的方法是使用抗体来阻断严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白的初始受体结合域（RBD），并避免其与宿主细胞结合。因此，开发这些靶向RBD的抗体将是治疗SARS-CoV-2传染病和阻止病毒复制的一种有前景的方法。大环表位更接近受体的实际拓扑结构，因此有望成为产生抗体的优质表位。这项工作证明了表位的三维形状对所开发的针对SARS-CoV-2 RBD蛋白的抗体活性的重要影响。分子动力学研究表明，与线性表位相比，环状表位具有更高的稳定性，这反映在它们所产生抗体的活性上。事实上，与由线性肽形成的抗体相比，我们使用大环表位开发的抗体在与RBD蛋白结合方面表现出优越性。本研究结果为开发可用于抑制SARS-CoV-2活性并防止其繁殖的优质抗体提供了路线图。
