Volume 31, No 1, Jan 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 1, January 2021: 101-103   |  Open Access

LETTERS TO THE EDITOR

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

Nan Wang^1,2 , Yao Sun¹ , Rui Feng^1,2 , Yuxi Wang³ , Yan Guo⁴ , Li Zhang⁵ , Yong-Qiang Deng⁴ , Lei Wang¹ , Zhen Cui¹ , Lei Cao¹ , Yan-Jun Zhang⁶ , Weimin Li^3,* , Feng-Cai Zhu^5,* , Cheng-Feng Qin^4,* , Xiangxi Wang^1,2,7,*

¹CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
²University of Chinese Academy of Sciences, Beijing 100049, China
³Department of Respiratory and Critical Care Medicine, West China Medical School/West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
⁴State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, China
⁵National Health Commission of the People’s Republic of China, Key laboratory of Enteric Pathogenic Microbiology (Jiangsu Provincial Center for Disease Control and Prevention), Nanjing, Jiangsu 210009, China
⁶Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang 310000, China
⁷Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong 510200, China
Correspondence: Weimin Li(weimi003@scu.edu.cn)Feng-Cai Zhu(jszfc@vip.sina.com)Cheng-Feng Qin(qincf@bmi.ac.cn)Xiangxi Wang(xiangxi@ibp.ac.cn)

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.2,3,4,5 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 characterizations of S in complex with potential NAb cocktails reported recently inform strategies for the development of vaccines for protection against COVID-19.

https://doi.org/10.1038/s41422-020-00446-w

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