Graphical abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a novel beta coronavirus. SARS-CoV-2 uses spike glycoprotein to interact with host angiotensin-converting enzyme 2 (ACE2) and ensure cell recognition. High infectivity of SARS-CoV-2 raises questions on spike-ACE2 binding affinity and its neutralization by anti-SARS-CoV monoclonal antibodies (mAbs). Here, we observed Val-to-Lys417 mutation in the receptor-binding domains (RBD) of SARS-CoV-2, which established a Lys-Asp electrostatic interaction enhancing its ACE2-binding. Pro-to-Ala475 substitution and Gly482 insertion in the A GSTPCN G V-loop of RBD possibly hinders neutralization of SARS-CoV-2 by anti-SARS-CoV mAbs. In addition, we identified unique and structurally conserved conformational-epitopes on RBDs, which can be potential therapeutic targets. Collectively, we provide new insights into the mechanisms underlying the high infectivity of SARS-CoV-2 and development of effective neutralizing agents.
【저자키워드】 COVID-19, SARS-CoV-2, Spike protein, mAb, Therapeutic peptides, 【초록키워드】 coronavirus disease, ACE2, coronavirus, Mutation, neutralization, monoclonal antibody, spike glycoprotein, angiotensin-converting enzyme 2, binding affinity, RBD, Neutralizing, mechanism, mAbs, RBDs, acute respiratory syndrome, Abstract, insertion, potential therapeutic targets, beta coronavirus, Host, electrostatic interaction, effective, Cell, raise, conserved, addition, question, unique, the receptor-binding domain, cause, 【제목키워드】 RBD, cross-neutralization, ACE2 binding, responsible, the SARS-CoV-2,