Universal antikovid antibodies?
An antibody capable of neutralizing all known variants of the SARS-CoV-2 coronavirus has been identified
Maria Azarova, Naked Science
In addition to vaccines against Covid-19, experts are studying monoclonal antibodies – proteins obtained in laboratories that mimic the ability of the immune system to fight the antigen. Many similar drugs have previously shown efficacy in animals, and some have been approved for the treatment of patients in emergency departments. According to scientists, monoclonal antibody therapy is useful for patients at risk and will help vaccines to resist the pandemic.
Most antibodies to SARS-CoV-2 have neutralizing properties and prevent the virus from binding to human cells, that is, they act against the receptor-binding domain (RBD) of the S-protein of the causative agent Covid-19. At the same time, the researchers found inhibitory antibodies: they target the N-terminal domain (NTD) of the spike and the S2 domain (it is already responsible for fusion with the cell membrane and penetration into the cell). But as we know, the problem is that the virus is changing. And its new variants acquire mutations in the S-protein, thereby gaining resistance to monoclonal or polyclonal antibodies. Therefore, additional drugs that will be effective against SARS-CoV-2 strains are required for the treatment of patients.
Employees of Washington University Medical School in St. Louis have identified an antibody to the receptor-binding domain of SARS-CoV-2, capable of overcoming all currently known variants of the virus. A preprint of the work is published in the journal Immunity (VanBlargan et al., A potentially neutralizing SARS-CoV-2 antibody inhibits variations of concern by utilizing unique binding residues in a highly conserved epitope). The researchers started with experiments on mice, injecting them with a key part of the spike–like protein - the receptor-binding domain. Then the antibody-producing cells were extracted and 43 antibodies were obtained, nine of which were tested on rodents.
While some proteins demonstrated limited ability to protect against infection with the "classic" Wuhan strain, others were effective during prophylactic or therapeutic administration. And two antibodies – SARS2-02 and SARS2-38 – were able to neutralize the virus strains of concern. The first binds the epitope, which includes residues E484 and L452, but demonstrates reduced effectiveness against variants B.1.351 ("beta"), B.1.617.2 ("delta"), B.1.429 ("epsilon"), B.1.1.28/P.1 ("gamma"), B.1.526 80 ("iota") and B. 1.617.1 ("kappa") encoding these mutations. The second antibody, on the contrary, bound the epitope to the center on the residues K444 and G446 – and neutralized all the above-mentioned strains.
A picture from an article in Immunity – VM.
"Analysis of the structure of SARS2-38 showed that this antibody binds to a conservative epitope on RBD (that is, common to various strains. – Ed. note). Thus, targeting this conservative domain area can provide protection against all emerging variants of the virus," the biologists write. At the same time, SARS2-38 has a high neutralizing ability, which means it works well even at low concentrations. "This is an unusual combination for an antibody. Plus, it binds to a unique site of the S-spike protein, which is not targeted by other antibodies. It would be possible to consider combining SARS2-38 with other similar proteins to create a combination therapy," the authors concluded.
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