On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

Autor(es)

Giron, Carolina Correa ^{[1, 2]} ; Laaksonen, Aatto ^{[3, 4, 5, 6]} ; Barroso da Silva, Fernando L. ^{[7, 2, 8]}

Afiliação do(s) autor(es)

^[1] Univ Fed Triangulo Mineiro, Dept Saude Colet, Rua Vigario Carlos, BR-38025350 Uberaba, MG - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Biomol, Av Cafe S-No, Campus USP, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Stockholm Univ, Dept Mat & Environm Chem, Arrhenius Lab, SE-10691 Stockholm - Sweden

^[4] Nanjing Tech Univ, State Key Lab Mat Oriented & Chem Engn, Nanjing 210009 - Peoples R China

^[5] Petru Poni Inst Macromol Chem, Ctr Adv Res Bionanoconjugates & Biopolymers, Aleea Grigore Ghica Voda 41A, Iasi 700487 - Romania

^[6] Lulea Univ Technol, Dept Engn Sci & Math, Div Energy Sci, SE-97187 Lulea - Sweden

^[7] North Carolina State Univ, Dept Chem & Biomol Engn, Raleigh, NC 27695 - USA

^[8] North Carolina State Univ, Dept Chem & Biomol Engn, Raleigh, NC 27695 USA.Giron, Carolina Correa, Univ Fed Triangulo Mineiro, Dept Saude Colet, Rua Vigario Carlos, BR-38025350 Uberaba, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: VIRUS RESEARCH; v. 285, AUG 2020.
• Citações Web of Science: 1

Resumo

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. (AU)

• Processo FAPESP: 15/16116-3 - Mecanismos moleculares de origem eletrostática responsáveis pela complexação de proteínas
• Beneficiário: Fernando Luis Barroso da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular