Sotrovimab receives FDA emergency use authorization for "broad-spectrum" treatment of mild to moderate COVID-19

On May 26, the US FDA granted emergency use authorization (EUA) for the COVID-19 monoclonal antibody drug sotrovimab for mild to moderate patients who tested positive for the virus and have a high risk of developing severe COVID-19 (including hospitalization and death) Adults and adolescents (12 years and older, weighing at least 40 kg) patients [1].

Sotrovimab is a neutralizing antibody developed by GlaxoSmithKline (GSK) and Vir Biotechnology (hereinafter referred to as Vir).

Neutralizing antibodies-a "new weapon" against the new crown

In terms of the development of therapies to fight the new crown epidemic, the development of neutralizing antibodies has always been one of the focuses of research and development [2].

The neutralizing antibody can prevent the new coronavirus from infecting cells by binding to the spike protein of the new coronavirus.

Compared with the vaccine, its advantage is that it can take effect immediately after receiving the injection, and it is equally effective for people who may not be able to produce an adequate immune response to the vaccine (including some elderly people and patients with suppressed immune systems).

Discovery of Sotrovimab neutralizing antibody

Sotrovimab is a new type of coronavirus (SARS-CoV-2) monoclonal antibody with dual effects.

It binds to a highly conserved epitope on the antibody binding domain (RBD) of the spike protein, not only has the activity of neutralizing SARS-CoV-1, but also has the ability to neutralize the new coronavirus and other coronaviruses.

Highly conserved epitopes as targets for the development of neutralizing antibodies

Researchers found that the epitope that S309 binds to the new coronavirus S protein (the S protein helps the virus enter human cells) is very conserved in the new coronavirus.

Studies believe that the mutations in these four virus strains do not affect the binding of S309 to the S protein.

By optimizing the Fc terminal, prolong the half-life and enhance active immunity

Vaccines stimulate the body's adaptive immune response, allowing the body to produce antibodies and immune cell responses against the new coronavirus, which we call "active immunity".

In order to overcome the short-duration problem, during the development of sotrovimab, the Fc end of the sotrovimab monoclonal antibody was further optimized by using XmAb antibody engineering technology, which not only prolonged the half-life of the neutralizing antibody, but also gave sotrovimab promotion The ability of dendritic cells to mature and activate CD8-positive T cells.

The phase III clinical trial was terminated early due to good efficacy

In March of this year, Vir and GlaxoSmithKline jointly announced that based on the results of a positive interim analysis of sotrovimab (VIR-7831), the Independent Data Monitoring Committee (IDMC) recommended the early termination of sotrovimab for the treatment of high-risk COVID-19 patients III Phase clinical trials.

In this clinical trial, a total of 583 patients received sotrovimab monotherapy or placebo.

"Broad-spectrum anti-drug", maintains activity against a variety of new crown variants

As the COVID-19 epidemic continues, the new coronavirus continues to produce new mutant strains.

At present, the genetic mutations carried by a variety of mutant virus strains that have received attention have shown the potential to evade the neutralizing activity of antibodies.

On the occasion of the COVID-19 pandemic, we hope that more new crown vaccines and therapies will be developed to help control the epidemic as soon as possible, and let the people of the world return to normal life.

reference:

1.
FDA authorizes Vir-GSK antibody as variants threaten Eli Lilly mAb;

2.
Identification and Characterization of a Potential Therapeutic COVID-19 Antibody by Vir Biotechnology Published in Nature.
Retrieved May 18, 2020, from https:// /en/Identification-and-Characterization-of-a-Potential-Therapeutic-COVID-19-Antibody-by-Vir-Biotechnology-Published-in-Nature.
html;

3.
Fozouni et al.
, Direct detection of SARS-CoV-2 using CRISPR-Cas13a and a mobile phone.
medRxiv, doi: https://doi.
org/10.
1101/2020.
09.
28.
20201947;

4.
Vir Biotechnology and GSK announce VIR-7831 reduces hospitalisation and risk of death in early treatment of adults with COVID-19.
Retrieved March 11, 2021, from https:// -releases/vir-biotechnology-and-gsk-announce-vir-7831-reduces-hospitalisation-and-risk-of-death-in-early-treatment-of-adults-with-covid-19/;

5.
Vir Biotechnology and GSK announce VIR-7831 reduces hospitalisation and risk of death in early treatment of adults with COVID-19.
Retrieved March 11, 2021, from https:// -releases/vir-biotechnology-and-gsk-announce-vir-7831-reduces-hospitalisation-and-risk-of-death-in-early-treatment-of-adults-with-covid-19/.