Broad Sarbecovirus Neutralizing Antibodies Obtained by Computational Design and Synthetic Library Screening
Xuehua Yang, Huarui Duan, Xiuying Liu, Xinhui Zhang, Shengnan Pan, Fangyuan Zhang, Peixiang Gao, Бо Лю, Jian Yang, Xiaojing Chi, Wei Yang
Abstract
includes human SARS-CoV, SARS-CoV-2, and hundreds of genetically related bat viruses. The continuous evolution of SARS-CoV-2 has led to the striking evasion of neutralizing antibody (NAb) drugs and convalescent plasma. Antibodies with broad activity across sarbecoviruses would be helpful to combat current SARS-CoV-2 mutations and longer term animal virus spillovers. The study of pan-sarbecovirus NAbs described here is significant for the following reasons. First, we established a structure-based computational pipeline to design and optimize NAbs to obtain more potent and broader neutralizing activity across multiple sarbecoviruses. Second, we screened and identified nanobodies from a highly diversified synthetic library with a broad neutralizing spectrum using an elaborate screening strategy. These methodologies provide guidance for the rapid development of antibody therapeutics against emerging pathogens with highly variable characteristics.