Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections

doi:10.1007/s11684-021-0847-4

Front. Med.

2021, Vol. 15

Issue (4) : 644-648 https://doi.org/10.1007/s11684-021-0847-4

LETTER TO FRONTIERS OF MEDICINE

Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections

Rongtao Lai, Tianhui Zhou, Xiaogang Xiang, Jie Lu, Haiguang Xin(

), Qing Xie(

)

Department of Infectious Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

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Abstract

The coronavirus disease 2019 (COVID-19) has caused global public health and economic crises. Thus, new therapeutic strategies and effective vaccines are urgently needed to cope with this severe pandemic. The development of a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the attractive treatment strategies for COVID-19. Currently, the receptor-binding domain (RBD) of the spike (S) protein is the main target of neutralizing antibodies when SARS-CoV-2 enters human cells through an interaction between the S protein and the angiotensin-converting enzyme 2 expressed on various human cells. A single monoclonal antibody (mAb) treatment is prone to selective pressure due to increased possibility of targeted epitope mutation, leading to viral escape. In addition, the antibody-dependent enhancement effect is a potential risk of enhancing the viral infection. These risks can be reduced using multiple mAbs that target nonoverlapping epitopes. Thus, a cocktail therapy combining two or more antibodies that recognize different regions of the viral surface may be the most effective therapeutic strategy.

Keywords neutralizing antibody antibody cocktail SARS-CoV-2 COVID-19 therapeutic strategy

Corresponding Author(s): Haiguang Xin,Qing Xie

Just Accepted Date: 26 March 2021 Online First Date: 27 April 2021 Issue Date: 23 September 2021

Cite this article:

Rongtao Lai,Tianhui Zhou,Xiaogang Xiang, et al. Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections[J]. Front. Med., 2021, 15(4): 644-648.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-021-0847-4
https://academic.hep.com.cn/fmd/EN/Y2021/V15/I4/644

Fig.1 Mechanism of the cocktail therapy of neutralizing antibodies for treating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Neutralizing antibodies (blue) target different epitopes of the S1 subunit of SARS-CoV-2, intercepting the virus from binding to ACE2 on the surface of human cells, thereby preventing the virus from entering the host cell. The S2 subunit enters the human cell membrane as the viral fusion peptide, thereby inducing a conformational change in the S2 subunit and forms a 6-HB trimer with HR1 and HR2 domains in the virus fusion stage. Neutralizing antibodies (purple) disturb the 6-HB formation by binding the HR1 domain to inhibit the fusion of SARS-CoV-2 and host cell. ACE2, angiotensin-converting enzyme 2; 6-HB, 6-helix bundle; HR1, heptad repeat 1; HR2, heptad repeat 2.

Clinical trial identifier	Study type	Estimated enrollment	Subjects	Treatment	Primary objectives
NCT04425629	Randomized/double-blind study	2104	Ambulatory patients with COVID-19	Low-dose REGN10933+ REGN10987, high-dose REGN10933+ REGN10987	To evaluate the clinical efficacy of REGN10933+ REGN10987 compared with placebo
NCT04426695	Randomized/double-blind study	2970	Hospitalized adult patients with COVID-19	REGN10933+ REGN10987	Proportion of patients with treatment-emergent serious adverse events
NCT04452318	Randomized/double-blind study	2000	Asymptomatic adults with SARS-CoV-2 infection	?REGN10933+ REGN10987	Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and signs and symptoms of SARS-CoV-2 infection during the efficacy assessment period
NCT04427501	Randomized/double-blind study	800	Patients with mild to moderate COVID-19	LY3819253 (LY-CoV555) or LY3819253+ LY3832479 (LY-CoV016)	Change in SARS-CoV-2 viral load from baseline to day 11
?NCT04545060	Randomized/double-blind study	1360	Nonhospitalized patients with COVID-19	Monoclonal antibody?VIR-7831	Proportion of participants who have progression of COVID-19 until day 29
NCT04390464	Randomized/open-label study	1167	Admitted pre-ICU patients with?COVID-19	Ravulizumab (monoclonal antibody that binds to the terminal complement protein C5) or baricitinib (antirheumatic drug)	Time to incidence of the composite endpoint of death, mechanical ventilation, ECMO, cardiovascular organ support, or renal failure
NCT04634409	Randomized/double-blind study	500	Participants with mild to moderate?COVID-19?	LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016)	Percentage of participants with SARS-CoV-2 viral load higher than 5.27
?NCT04381936	Randomized/open-label study	15 000	Patients with COVID-19	Drug: lopinavir–ritonavir Drug: corticosteroid Drug: hydroxychloroquine Drug: azithromycin Biological: convalescent plasma Drug: tocilizumab Biological: immunoglobulin Drug: synthetic neutralizing antibodies	All-cause mortality (within 28 days after randomization)

Tab.1 Eight registered clinical trials of neutralizing mAbs with therapeutic potential against SARS-CoV-2

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