Abstract
Coronavirus disease 2019, caused by SARS-CoV-2, remains an on-going pandemic, partly due to the emergence of variant viruses that can “break-through” the protection of the current vaccines and neutralizing antibodies (nAbs), highlighting the needs for broadly nAbs and next-generation vaccines. We report an antibody that exhibits breadth and potency in binding the receptor-binding domain (RBD) of the virus spike glycoprotein across SARS coronaviruses. Initially, a lead antibody was computationally discovered and crystallographically validated that binds to a highly conserved surface of the RBD of wild-type SARS-CoV-2. Subsequently, through experimental affinity enhancement and computational affinity maturation, it was further developed to bind the RBD of all concerning SARS-CoV-2 variants, SARS-CoV-1 and pangolin coronavirus with pico-molar binding affinities, consistently exhibited strong neutralization activity against wild-type SARS-CoV-2 and the Alpha and Delta variants. These results identify a vulnerable target site on coronaviruses for development of pan-sarbecovirus nAbs and vaccines.
Keywords: Computational antibody discovery; Sars-CoV-2; broad-spectrum vaccine; broadly neutralizing antibody; emerging variants.
【저자키워드】 SARS-CoV-2, Broadly neutralizing antibody, Computational antibody discovery, broad-spectrum vaccine, emerging variants., 【초록키워드】 coronavirus disease, viruses, neutralizing antibody, Coronavirus disease 2019, Vaccine, coronavirus, pandemic, Vaccines, Neutralizing antibodies, antibody, variant, spike glycoprotein, Delta, SARS-CoV-1, variants, Receptor-binding domain, SARS-CoV-2 variants, RBD, Alpha, Neutralizing, glycoprotein, Affinity maturation, NAb, breadth, Delta variants, SARS coronaviruses, lead, binding affinities, NAbs, domain, neutralization activity, potency, wild-type SARS-CoV-2, alpha and delta variants, Virus spike, bind, identify, caused, virus, conserved, exhibited, coronavirus, the RBD, concerning, exhibit, highlighting, binding the receptor-binding, Initially, 【제목키워드】 SARS-CoV-2 variant, binding affinity, concerning,