Science and Technology Unit, Umm Al-Qura University, P.O. Box 715, Mecca, 21955, Kingdom of Saudi Arabia.
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 715, Mecca, 21955, Kingdom of Saudi Arabia.
Mol Divers. 2023 Apr;27(2):695-708. doi: 10.1007/s11030-022-10449-x. Epub 2022 May 26.
SARS, or severe acute respiratory syndrome, is caused by a novel coronavirus (COVID-19). This situation has compelled many pharmaceutical R&D companies and public health research sectors to focus their efforts on developing effective therapeutics. SARS-nCoV-2 was chosen as a protein spike to targeted monoclonal antibodies and therapeutics for prevention and treatment. Deep mutational scanning created a monoclonal antibody to characterize the effects of mutations in a variable antibody fragment based on its expression levels, specificity, stability, and affinity for specific antigenic conserved epitopes to the Spike-S-Receptor Binding Domain (RBD). Improved contacts between Fv light and heavy chains and the targeted antigens of RBD could result in a highly potent neutralizing antibody (NAbs) response as well as cross-protection against other SARS-nCoV-2 strains. It undergoes multipoint core mutations that combine enhancing mutations, resulting in increased binding affinity and significantly increased stability between RBD and antibody. In addition, we improved. Structures of variable fragment (Fv) complexed with the RBD of Spike protein were subjected to our established in-silico antibody-engineering platform to obtain enhanced binding affinity to SARS-nCoV-2 and develop ability profiling. We found that the size and three-dimensional shape of epitopes significantly impacted the activity of antibodies produced against the RBD of Spike protein. Overall, because of the conformational changes between RBD and hACE2, it prevents viral entry. As a result of this in-silico study, the designed antibody can be used as a promising therapeutic strategy to treat COVID-19.
非典,又称严重急性呼吸综合征,是由一种新型冠状病毒(COVID-19)引起的。这种情况迫使许多制药研发公司和公共卫生研究部门将精力集中在开发有效的治疗方法上。SARS-nCoV-2 被选为靶向单克隆抗体和治疗药物的蛋白刺突,用于预防和治疗。深突变扫描产生了一种单克隆抗体,用于根据其表达水平、特异性、稳定性以及与 Spike-S-受体结合域(RBD)的特定抗原保守表位的亲和力来表征可变抗体片段突变的影响。Fv 轻链和重链与 RBD 的靶向抗原之间的改进接触可能导致高效的中和抗体(NAbs)反应以及对其他 SARS-nCoV-2 株的交叉保护。它经历多点核心突变,结合增强突变,导致 RBD 和抗体之间的结合亲和力显著增加,稳定性显著提高。此外,我们改进了。与 Spike 蛋白 RBD 结合的可变片段(Fv)结构被提交给我们现有的计算机抗体工程平台,以获得对 SARS-nCoV-2 的增强结合亲和力并开发能力分析。我们发现表位的大小和三维形状显著影响针对 Spike 蛋白 RBD 产生的抗体的活性。总的来说,由于 RBD 和 hACE2 之间的构象变化,它阻止了病毒的进入。由于这项计算机研究,设计的抗体可以用作治疗 COVID-19 的有前途的治疗策略。