A monoclonal antibody capable of neutralizing the SARS-CoV-2 virus in the laboratory is reported in a paper published in Nature Communications. Further studies are needed to explore whether these findings could potentially be translated to the clinic.
Antibodies that neutralize coronaviruses tend to target the trimeric spike (S) protein on the surface of the virus, which mediates entry into host cells. The S protein consists of two subunits: S1 and S2, which are involved in attachment to the cell and fusion of the viral and cell membranes, respectively. The S proteins of SARS-CoV-2 (Wuhan-Hu-1 strain) and SARS-CoV (Urbani strain) have amino acid sequences that are 77.5% identical and are structurally very similar. These viruses are known to bind to the protein ACE2 on the surface of human cells through the S1B domain (one of the 4 core domains of S1) of their spike proteins.
In order to identify antibodies that could potentially neutralize SARS-CoV-2, Berend-Jan Bosch and colleagues created 51 cell lines from humanized mice that produced antibodies to the S protein of different coronaviruses. They then performed an assay of the chimeric antibodies (derived from humans and rats) collected to determine if any were capable of neutralizing SARS-CoV-2. The authors found that one antibody (47D11) showed neutralizing activity for both SARS-CoV and SARS-CoV-2. This chimeric antibody was then reformatted to produce a fully human version of the antibody.
In addition, the authors demonstrated in cell culture that 47D11 targets the S1B receptor binding domain of both SARS-CoV and SARS-CoV-2. However, they observed that the binding of 47D11 did not interfere with S1B attachment to ACE2. This suggests that 47D11 neutralizes SARS-CoV-2 and SARS-CoV through a different mechanism to receptor-binding interference. Further work to determine the precise mechanism is needed. The authors suggest that 47D11, either alone or in combination with other neutralizing antibodies that target the receptor binding subdomain, could potentially aid the development of therapeutic strategies in the future.
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