Good News! A Cross-Neutralizing Human Antibody Blocking Sars-Cov-2 Infection Offers Potential for Prevention and Treatment of Covid-19
The outbreak of the novel human coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) caused a worldwide epidemic of respiratory diseases (COVID-19). At this stage, scientists are constantly discovering and developing vaccines and targeted therapeutics for treatment of the disease. As a kind of promising anti-infective drugs, monoclonal antibodies have been widely used in the treatment of many kinds of viruses. The good news came from researchers in the Netherlands and Germany, who reported a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV), 47D11. This cross-neutralizing antibody targets the common epitope of these viruses, providing potential for the prevention and treatment of COVID-19.
Chunyan Wang et al. pointed out that the neutralizing antibodies of coronavirus are mainly aimed at the trimer spike (S) glycoproteins on the viral surface that mediate entry into the host cell. The S protein has two functional subunits: cell adhesion (S1) and virus membrane fusion (S2). The S protein has two functional subunits: S1, which mediates cell attachment and S2, which mediates the fusion of virus and cell membrane.
Effective neutralizing antibodies often target the receptor interaction site in S1, which makes the receptor interaction ineffective. The S protein of SARS-CoV-2 and SARS-CoV has 77.5% consistency in the primary amino acid sequence, which is very similar in structure. It usually binds to human angiotensin coverting enzyme 2 (ACE2) protein as host receptor through its S1B domain.
In order to identify the neutralizing antibody of SARS-CoV-2, the researchers evaluated the antibody-containing supernatants of a group of SARS-S hybridoma’s by ELISA (cross) reactivity and selected an antibody (47D11) which can bind to the cells expressing the full-length S proteins of SARS-CoV and SARS-CoV-2.
Congruent with the ELISA-reactivities, the binding kinetics of 47D11 with the S ectodomain (Secto) of SARS was determined by biological layer interference method, which showed that 47D11 binds SARS Secto with higher affinity. Using a trypsin-triggered cell-cell fusion assay, 47D11 was shown to impair SARS-S and SARS2-S mediated syncytial formation.
Multiple experimental data showed that 47D11 neutralized SARS-CoV and SARS-CoV-2 through an unknown mechanism different from receptor binding interference. The alternative mechanism of receptor binding domain (RBD)-targeting antibody neutralizing coronavirus has been reported, including the inactivation of the S by the destabilization of its prefusion structure induced by antibody, which may also be applicable to 47D11.
47D11 binds to the conserved epitopes on the spike receptor binding domain, which explains its ability to cross-neutralize SARS-CoV and SARS-CoV-2 using mechanisms independent of receptor binding inhibition.
This is the first time that monoclonal antibodies (human) have been reported to neutralize SARS-CoV-2. The 47D11 in this report can be used for SARS-CoV-2 antigen detection and serological detection. Neutralizing antibodies can change the infection process of infected host, so as to support virus clearance or protect uninfected host. As a result, 47D11 has great potential to become a star molecule in the prevention and / or treatment of COVID-19, as well as other future emerging diseases in human beings.
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Reference
- Wang, Chunyan, et al. "A human monoclonal 1 antibody blocking SARS-CoV-2 infection." Biorxiv (2020).
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