Universidade Federal do Triângulo Mineiro, Departamento de Saúde Coletiva, Rua Vigário Carlos, 38025-350 Uberaba, MG, Brazil; Universidade de São Paulo, Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Av. café, s/no - campus da USP, BR-14040-903 Ribeirão Preto SP, Brazil.
Department of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden; State Key Laboratory of Materials-Oriented and Chemical Engineering, Nanjing Tech University, Nanjing, 210009, PR China; Centre of Advanced Research in Bionanoconjugates and Biopolymers, Petru Poni Institute of Macromolecular Chemistry, Aleea Grigore Ghica-Voda, 41A, 700487 Iasi, Romania; Department of Engineering Sciences and Mathematics, Division of Energy Science, Luleå University of Technology, SE-97187 Luleå, Sweden.
Virus Res. 2020 Aug;285:198021. doi: 10.1016/j.virusres.2020.198021. Epub 2020 May 15.
A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.
一种名为 SARS-CoV-2 的新型β冠状病毒已成为全球健康和经济的新威胁。一种名为 COVID-19 的新疾病的诊断和治疗的有希望的靶点是冠状病毒（CoV）刺突（S）糖蛋白。通过恒 pH 蒙特卡罗模拟和 PROCEEDpKa 方法，我们已经绘制了针对四种单克隆抗体和血管紧张素转换酶 2（ACE2）的静电表位，这些抗体和 ACE2 都位于 SARS-CoV-1 和新型 SARS-CoV-2 S 受体结合域（RBD）蛋白上。我们还计算了相互作用的自由能，并表明来自两种 SARS 病毒的 S RBD 蛋白与 ACE2 的结合亲和力相似。然而，新型 SARS-CoV-2 的 S RBD 蛋白与 ACE2 的亲和力高于以前与 SARS-CoV-1 复合的任何研究抗体。基于物理化学分析和自由能估计，我们可以阐明所涉及的分子识别过程、它们的临床方面、对药物开发的影响，并对 CR3022 抗体进行结构修饰，以提高其对 SARS-CoV-2 的结合亲和力，并有助于解决正在发生的国际卫生危机。
