Virology: Current Research

ISSN: 2736-657X

Open Access

Broadly Potent Neutralizing Bispecific Antibody against SARS-CoV-2


Hui Zhang, Haohui Huang, Rong Li, Lu Zhang, Zhiwei Wang, Shide Liang, Jiaping Li, Junyou Chen, Huafei Su, Dandan Zheng, Ziqi Su, Li Wang, Xiong Mei, Shujun Pei, Shenghua Zhu, Chan Li, Yaochang Yuan, Haitao Yue, Yanqun Wang, Xiaobo Li, Cuihua Liu, Jinchen Yu, Hui Zhang, Shengfeng Li and Xianming Huang*

The Omicron variant of Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) is threatening our global efforts fighting the COVID-19 pandemic. As the vast majority of current countermeasures against SARS-CoV-2 are completely or markedly losing their effectiveness, including most of the clinically approved neutralizing antibodies, better and more efficacious novel agents are urgently needed. We have developed a bispecific antibody, BAT2022, which bonds simultaneously with high affinity to two non-overlapping epitopes on the Receptor-Binding Domain (RBD), competitively blocks the binding of RBD to human Angiotensin-Converting Enzyme2 (ACE2) and potently neutralizes SARS-CoV-2 and all of the variants tested. The IC50 values in the pseudovirus assay for Omicron (BA.1) and Delta are 30 pM and 50 pM, respectively. A mouse model of SARS-CoV-2, BAT2022 showed strong prophylactic and therapeutic effects. Prophylactically, a single administration of BAT2022 completely protected mice from bodyweight loss, as compared with up to 20% loss of body weight in placebo- treated mice, reduced the lung viral titers to undetectable in all mice treated with BAT2022 either prophylactically or therapeutically, as compared with around 1 × 105 pfu/g lung tissue in placebo-treated mice. Overall, Bispecific Antibody BAT2022 showed potent binding and neutralizing activity across a variety of SARS- CoV-2 variants and could be an attractive weapon to combat the ongoing waves of the Omicron pandemic.


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