A bispecific antibody designed by a Swiss-Czech research team inhibited viral escape of SARS-CoV-2 mutations in animals.
The team called Daniel Ruzek or Luca Varani from the University of Bellinzona and the Czech Academy of Sciences focused on two binding sites within the receptor binding domain (RBD) of SARS-CoV-2 Spike (S) protein to inhibit on a generation of viral survivors. . The engineered bispecific molecule, similar to IgG1 (CoV-X2) based on two antibodies derived from COVID-19 convalescent donors, C121 and C135, in vitro inhibited S-binding of a known to Angiotensin-Converting Enzyme 2 (ACE2 ), the viral cell receptor.
In addition, CoV-X2 neutralized SARS-CoV-2 and its anxiety variants, as well as the escape mutants generated by parental monoclonals. In a modern animal model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protected mice from infection that eliminated the generation of viral escape variants. Thus, simultaneous targeting of non-overlapping RBD epitopes with bispecific antibodies similar to IgG is feasible and effective, combining in single molecules the benefits of antibody cocktails.
At the same time, because funding in Europe for Phase III registration trials is not expensive for COVID-19 treatment, such as monoclonal and bispecific antibodies or therapeutic treatment for the same purpose, European companies are moving to the United States. As part of BARDA group Activ3 billion-dollar program to develop and reproduce promising COVID-19 antibodies, Swiss pharmaceutical company Novartis AG recently received funding for a Phase III trial of the antiviral substance Darpin MP0420 (Ensovibep) , which was shortly before approved by Molecular Partners AG for upwards of $ 69 million. Ensovibep is a small molecule constructed with an antibody-binding affinity that simultaneously binds to three sites on the receptor binding domain (RBD) of SARS-CoV-2 spike proteins to inhibit the virus from entering cells.
According to virologists, escape mutants are likely to decrease with the number of viral targets and binding sites within target proteins. The reason for this is that the viruses are completely eradicated, rather than simply reduced in number. This protects against the development of mutant viral strains.