A nasal antibody cocktail binding to the conserved S2 stalk region of SARS-COV-2 might end the corona pandemic.
In experiments, the candidate eliminated virus propagation of all SARS coronaviruses and of MERS,which occured in Saudi Arabia in 2012. If the researchers from UAB Texas and Aridis Biopharmaceuticals, which wants to commercialise an antibody cocktail dubbed AR-701, are able to confirm results resported in
PLoS Pathogens (doi: 10.1371/journal.ppat.1010691) a potent universal coronavirus therapy against SARS-CoV-2 and all its variants of concern might result.
In contrast to current antibodies or vaccines that target the receptor-binding region of the spike protein of SARS-CoV-2 variants, the antibodies identified by the researchers bind to the more conserved S2 region of the protein. A publication of a competing British group recommending exactly to use a mixture of antibodies that target both the S1 and the S2 regions will be published this week.
In a screening of blood from patients that recovered from an infection with SARS-CoV-2, the US team headed by James Kobie from the University of Alabama in Birmingham, USA, identified 17 hmAbs binding to the S2 protein region. Only four of these were able to neutralise a SARS-CoV-2 pseudovirus and a live SARS-CoV-2, including the Beta and Omicron variants. The top performer (1249A8 hmAb) had the broadest and most potent neutralising activity, against strains that included the original Wuhan strain form China of SARS-CoV-2; the Beta, Gamma, Delta, Epsilon and Omicron variants; the SARS-CoV and MERS-CoV; and two common cold viruses.
The hmAb protected mice from SARS-CoV-2 symptoms, as measured by maintenance of body weight and clearance of virus from mouse lungs four days after infection. Furthermore, the 1249A8 hmAb showed synergism when used in combination with 1213H7, a hmAb discovered by the researchers that targets the RBD of the viral S glycoprotein. Aridis is using the two hmAbs in its AR-701 cocktail designed for inhaled delivery. AR-701 is engineered for long-acting effectiveness, potentially lasting a year or more when used in humans.
Various research groups are currently looking for antibodies that target unalterable regions of the spike protein. Such regions are located in the stalk region (S2). Mutations here could lead to instability and "breaking off" of the spike protein. Without spike protein, SARS-CoV-2 and other beta-coronaviruses are not able to infect cells. Therefore, there are regions in S2 that are suitable targets for broadly neutralising antibodies.
