Giron Carolina Corrêa, Laaksonen Aatto, Barroso da Silva Fernando Luís
Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Universidade Federal do Triângulo Mineiro, Hospital de Clínicas, Uberaba, MG, Brazil.
J Biomol Struct Dyn. 2023 Jul-Aug;41(12):5707-5727. doi: 10.1080/07391102.2022.2095305. Epub 2022 Jul 9.
SARS-CoV-2 remains a health threat with the continuous emergence of new variants. This work aims to expand the knowledge about the SARS-CoV-2 receptor-binding domain (RBD) interactions with cell receptors and monoclonal antibodies (mAbs). By using constant-pH Monte Carlo simulations, the free energy of interactions between the RBD from different variants and several partners (Angiotensin-Converting Enzyme-2 (ACE2) polymorphisms and various mAbs) were predicted. Computed RBD-ACE2-binding affinities were higher for two ACE2 polymorphisms (rs142984500 and rs4646116) typically found in Europeans which indicates a genetic susceptibility. This is amplified for Omicron (BA.1) and its sublineages BA.2 and BA.3. The antibody landscape was computationally investigated with the largest set of mAbs so far in the literature. From the 32 studied binders, groups of mAbs were identified from weak to strong binding affinities (e.g. S2K146). These mAbs with strong binding capacity and especially their combination are amenable to experimentation and clinical trials because of their high predicted binding affinities and possible neutralization potential for current known virus mutations and a universal coronavirus.Communicated by Ramaswamy H. Sarma.
随着新冠病毒新变种的不断出现，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）仍然是一种健康威胁。这项工作旨在拓展关于SARS-CoV-2受体结合域（RBD）与细胞受体及单克隆抗体（mAb）相互作用的知识。通过使用恒定pH值蒙特卡洛模拟，预测了不同变种的RBD与几个配体（血管紧张素转换酶2（ACE2）多态性及各种mAb）之间相互作用的自由能。对于通常在欧洲人中发现的两种ACE2多态性（rs142984500和rs4646116），计算得出的RBD-ACE2结合亲和力更高，这表明存在遗传易感性。对于奥密克戎（BA.1）及其亚系BA.2和BA.3，这种情况更为明显。本文用文献中迄今为止最大的一组mAb对抗体情况进行了计算研究。从32种研究的结合物中，鉴定出了从弱到强结合亲和力的mAb组（如S2K146）。这些具有强结合能力的mAb，尤其是它们的组合，因其对当前已知病毒突变和通用冠状病毒具有高预测结合亲和力及可能的中和潜力，适合进行实验和临床试验。由拉马斯瓦米·H·萨尔马传达。
