Antibody cocktail shows synergetic effects against SARS-CoV-2 Omicron in vitro and in vivo A recent research paper posted to the bioRxiv* preprint server demonstrated that a cocktail of two synergetic antibodies extensively neutralized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, including Omicron BA.1 and BA.2.

A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2. Image Credit: Kateryna Kon / ShutterstockStudy: A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2. Image Credit: Kateryna Kon / Shutterstock

The coronavirus disease 2019 (COVID-19) pandemic continues globally even after two years since its emergence. SARS-CoV-2 infections can be prevented and treated using neutralizing antibodies (NAbs). Despite this, emerging SARS-CoV-2 variants, such as Omicron, have dramatically reduced the effectiveness of the most commonly used NAbs.

Furthermore, existing reports suggest that no authorized NAbs, except the recently approved agent LY-CoV1404 (bebtelovimab), effectively target all Omicron variant sublineages. Thus, the discovery of conserved crucial SARS-CoV-2 epitopes and the selection of NAbs with extensive neutralizing capabilities are still desperately needed.

In the present study, the investigators conducted a single B-cell sorting from COVID-19 convalescent subjects to identify a NAb that widely targeted the spike (S) receptor-binding domain (RBD) protein of currently prevalent SARS-CoV-2 variants, like Delta and Omicron.

The scientists assessed the SARS-CoV-2 neutralizing capacity of 55A8 NAb and its combination with a NAb named 58G6 previously discovered by the authors. The team mixed 55A8 and 58G6 NAbs, establishing a complimentary cocktail or 2-cocktail. Further, they analyzed how well the 2-cocktail could neutralize the SARS-CoV-2 wild-type (WT), Omicron BA.2, Delta, and Omicron BA.1 pseudo and authentic viruses, except the Omicron BA.2 authentic virus.

The interactions between Omicron BA.1 S trimers and 55A8 were assessed using cryogenic electron microscopy (cryo-EM). In the 55A8 fragment antigen-binding (Fab)-BA.1 S structures and angiotensin-converting enzyme 2 (ACE2)-BA.1 S complexes, the up RBD was superimposed. The cryo-EM structures of Omicron BA.1 S trimers in a complex with 58G6 and 55A8 Fabs were determined to analyze the possibility of the 58G6 and 55A8 Fabs combination in-depth. The effects of 58G6 and 55A8 (2-cocktail) combination therapy on the Omicron infection were evaluated by in vivo and in vitro assessments.

The study results revealed 55A8, an extraordinarily potent SARS-CoV-2 antibody, via single B-cell sorting from COVID-19-recovered individuals that targeted the SARS-CoV-2 S protein RBD. The authors found that 55A8 bound with SARS-CoV-2 WT and Omicron BA.2 and BA.1 strains concurrently with 58G6.

Source: This news is originally published by medical

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