Blockade of SARS-CoV-2 spike protein-mediated cell–cell fusion using COVID-19 convalescent plasma

• Published in: Scientific reports Vol. 11; no. 1; pp. 5558 - 11
• Main Authors: Wang, Ling, Zhao, Juan, Nguyen, Lam N. T., Adkins, James L., Schank, Madison, Khanal, Sushant, Nguyen, Lam N., Dang, Xindi, Cao, Dechao, Thakuri, Bal Krishna Chand, Lu, Zeyuan, Zhang, Jinyu, Zhang, Yi, Wu, Xiao Y., El Gazzar, Mohamed, Ning, Shunbin, Moorman, Jonathan P., Yao, Zhi Q.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/326; ACE2; Adult; Angiotensin-converting enzyme 2; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Cell fusion; Cell Fusion - methods; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 - therapy; COVID-19 Serotherapy; Effector cells; Female; Fusion protein; Humanities and Social Sciences; Humans; Immunization, Passive - methods; Immunoglobulin G; Infectious diseases; Male; Membrane fusion; Membrane Fusion - drug effects; Middle Aged; Molecular modelling; multidisciplinary; Pandemics; Pandemics - prevention & control; Plasma; Plasma - chemistry; Proteins; Public health; Receptors, Virus - metabolism; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Virus Internalization - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-84840-3

The recent COVID-19 pandemic poses a serious threat to global public health, thus there is an urgent need to define the molecular mechanisms involved in SARS-CoV-2 spike (S) protein-mediated virus entry that is essential for preventing and/or treating this emerging infectious disease. In this study, we examined the blocking activity of human COVID-19 convalescent plasma by cell–cell fusion assays using SARS-CoV-2-S-transfected 293 T as effector cells and ACE2-expressing 293 T as target cells. We demonstrate that the SARS-CoV-2 S protein exhibits a very high capacity for membrane fusion and is efficient in mediating virus fusion and entry into target cells. Importantly, we find that COVID-19 convalescent plasma with high titers of IgG neutralizing antibodies can block cell–cell fusion and virus entry by interfering with the SARS-CoV-2-S/ACE2 or SARS-CoV-S/ACE2 interactions. These findings suggest that COVID-19 convalescent plasma may not only inhibit SARS-CoV-2-S but also cross-neutralize SARS-CoV-S-mediated membrane fusion and virus entry, supporting its potential as a preventive and/or therapeutic agent against SARS-CoV-2 as well as other SARS-CoV infections.