Structure-based development of human antibody cocktails against SARS-CoV-2

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2021,（1）
• 所属期刊栏目: LETTERS TO THE EDITOR
• 页码范围: 101-103
• 页数: 3页
• 语种: 英文

摘要

Dear Editor, The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in unprecedented public health and socioeconomic crises,requiring urgent developments of effective COVID-19 therapeutics and vaccines.Humoral immunity is essential for protection against coronavirus infections and passive immunization has been demonstrated to be effective in curing SARS-CoV-2-challenged nonhuman primates.1,2 A deep understanding of the molecular basis of neutralizing antibody(NAb)responses to SARS-CoV-2 could facilitate vaccine design and drug discovery.Spike(S)protein,the major protective antigen,utilizes its receptor-binding domain(RBD)to engage the host receptor ACE2 for viral entry into host cell.Subsequently,a number of RBD-targeting NAbs against SARS-CoV-2,which block the binding of S to ACE2 have been reported and characterized.2-5 However,a major concern is the emergence of numerous viral mutations within RBD,in particular,when selective pressure is applied in immunotherapies,resulting in resistance against these antibodies.Recently,two antibodies targeting N-terminal domain(NTD)of S exhibited potent neutralizing activities against SARS-CoV-2.6,7 When used in combination with RBD-targeting and NTD-directing NAbs,the protective effect was magnified.5,6 Thus,a combination of antibodies could not only increase the potency of protection,but also prevent viral escape of immune responses via mutations.These preliminary results highlight the benefits of using a cocktail of antibodies for treating COVID-19 and provide a framework for rational design of antibody cocktail therapeutics that target both RBD and NTD regions.Furthermore,the structural characteriza-tions of S in complex with potential NAb cocktails reported recently inform strategies for the development of vaccines for protection against COVID-19.