Sotrovimab Is Effective Against Omicron Variant of Coronavirus

Highlights

GlaxoSmithKline and Vir Biotechnology reported that sotrovimab maintains neutralizing activity against the Omicron variant of SARS-CoV-2, which is now generating incredible media hype. Public concern is that the Omicron could dramatically reduce the effectiveness of treatment and vaccination.

A study of the Omicron strain (B.1.1.529) in a pseudotyped viral system found that in vitro sotrovimab retained activity against its key mutations. These did not change the effects of sotrovimab binding to its target. This is consistent with previous deep mutation scanning data examining the effect of specific amino acid substitutions in SARS-CoV-2 on sotrovimab.

To ensure that sotrovimab is fully prepared to repel an Omicron attack, the partners will test the neutralizing activity of their drug against a combination of all mutations inherent to this variant of the coronavirus by the end of this year.

Sotrovimab was previously found to be successful against other strains of SARS-CoV-2, which, according to the World Health Organization (WHO) classification, are listed as “variants of concern”, such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Delta plus (AY.1/AY.2).

Omicron Variant: Latest Scientific News, Findings, Evidence, and Developments

Up-to-date scientific information about the new Omicron variant of SARS-CoV-2/COVID-19.

Update #1

GlaxoSmithKline and Vir Biotechnology have compiled an update regarding the ability of sotrovimab to counteract the Omicron variant of the new coronavirus SARS-CoV-2.

According to in vitro studies, sotrovimab retains neutralizing activity against the entire S protein of the Omicron variant. Preclinical data were obtained in a pseudotyped viral system that tested combinations of known Omicron mutations that included the maximum number of changes (37 mutations) identified to date in the S protein.

Neutralizing activity of sotrovimab against the Omicron decreased by a factor of 2.7 in terms of the half-maximal inhibitory concentration (IC₅₀), but overall, it is claimed that this does not change the high therapeutic efficacy of this monoclonal antibody in any way.

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What Is Sotrovimab

Sotrovimab, still generally an experimental drug, has already been approved for use in two dozen countries, including the United States, the United Kingdom, Japan, Russia, Spain, Brazil, and others. It is marketed under the brand name Xevudy.

Sotrovimab is indicated for the treatment of COVID-19 infection in adults and children (12 years of age and older weighing at least 40 kg), who do not require oxygen support (COVID-19 is of mild-to-moderate severity) and who are in the high-risk group for progression to severe disease, including hospitalization or death.

According to a final efficacy analysis of sotrovimab, it reduces the risk of hospitalization and/or death by 79%.

Sotrovimab: Mechanism of Action

Sotrovimab (VIR-7831) is a recombinant human IgG1 monoclonal antibody that neutralizes the novel coronavirus SARS-CoV-2.

Sotrovimab is a derivative of antibodies isolated from memory B-cells of a patient who survived the severe acute respiratory syndrome (SARS) caused by the SARS-CoV-1 coronavirus from the 2003 sample.

Sotrovimab is targeted to the highly conserved epitope of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. The choice of the target, which is unlikely to ever seriously mutate the indicated epitope, allows us to safely assume that sotrovimab retains therapeutic efficacy against various variants of coronavirus, current and forthcoming.

Sotrovimab recognizes the epitope containing the glycan at position N343. This epitope, which is highly conserved in SARS-like coronaviruses of the Sarbecovirus subgenus, including SARS-CoV-2 and SARS-CoV-1, is in a region of RBD that does not compete with angiotensin-converting enzyme 2 (ACE2) binding.

Extras

The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2. bioRxiv, December 07, 2021. [source] [PDF]

The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2. bioRxiv, December 01, 2021. [source] [PDF]

Effect of the neutralizing SARS-CoV-2 antibody sotrovimab in preventing progression of COVID-19: a randomized clinical trial. medRxiv, November 08, 2021. [source] [PDF]

Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab. N Engl J Med. 2021 Nov 18;385(21):1941-1950. [source] [PDF]

Xevudy (sotrovimab). Prescribing information. USA. [PDF]

Xevudy (sotrovimab). Prescribing information. UK. [PDF]

Xevudy (sotrovimab). Prescribing information. Canada. [PDF]

Xevudy (sotrovimab). Prescribing information. Australia. [PDF]

Xevudy (sotrovimab). Prescribing information. Spain. [PDF]

Xevudy (sotrovimab). Prescribing information. Japan. [PDF]