Volume 31, No 5, May 2021

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

Volume 31 Issue 5, May 2021: 597-600   |  Open Access

LETTERS TO THE EDITOR

Structure-based development of three- and four-antibody cocktails against SARS-CoV-2 via multiple mechanisms

Yao Sun¹ , Lei Wang^1,2 , Rui Feng^1,2 , Nan Wang^1,2 , Yuxi Wang³ , Dandan Zhu¹ , Xiaorui Xing¹ , Peng Yang^1,2 , Yanjun Zhang^4,* , Weimin Li^3,* , Xiangxi Wang^1,2,5,*

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
⁴Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang 310000, China
⁵Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong 510200, China
Correspondence: Yanjun Zhang(yjzhang@cdc.zj.cn)Weimin Li(weimi003@scu.edu.cn)Xiangxi Wang(xiangxi@ibp.ac.cn)

Dear Editor,

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in an unprecedented public health crisis, galvanizing a global effort for rapidly developing new therapeutic strategies effective against COVID-19. Human monoclonal antibodies (mAbs) are promising therapeutic molecules that can be used for the prevention or treatment of viral infectious diseases, including COVID-19. For instance, ZMappTM, a cocktail consisting of three different mAbs targeting the Ebola glycoprotein is one of the most successful antibody-based therapeutic for treating infections caused by Ebola virus.1 Notably, this cocktail combines the best-performing neutralizing antibodies (NAbs) screened and developed using two separate approaches, one from humanized antibodies of origin and the other from human survivors. The success of these methods indicates critical roles played by NAb diversity in the design of antibody cocktails. Cocktail therapies are not only a source of ultra-potent neutralizing activities, but they also offer advantage in overcoming potential drug resistance issues arising out of the rapid mutation of viral pathogens, in particular when selective pressure is applied. Concerningly, the emerged and rapidly spreading SARS-CoV-2 variants have arisen in the United Kingdom (UK), South Africa (SA) and other regions, such as more recently reported B.1.1.7 (UK strain, variant of concern, VOC202012/01) and 501Y.V2 (SA strain, VOC501Y.V2). These variants contain multiple mutations in their spike proteins (S), some of which are key targets of NAbs, highlighting the tremendous potential of multiple antibody-based cocktails in treating SARS-CoV-2 infection.

https://doi.org/10.1038/s41422-021-00497-7

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