Receptor Binding and Escape From Beta Antibody Responses Drive Omicron-B.1.1.529 Evolution

On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced. Omicron contains a total of 30 substitutions plus deletions and an insertion in Spike, far more than any previously reported variant. The mutations include those previously identified by In-vitro evolution to contribute to high-affinity binding to ACE2, including mutations Q498R and N501Y critical in forming additional interactions in the interface. Together with increased charge complementarity between the RBD and ACE2, these substantially increase affinity and potentially virus transmissibility through increased syncytia formation. Further mutations promote immune evasion. We have studied the binding of a large panel of potent monoclonal antibodies generated from early pandemic or Beta infected cases. Mutations in Omicron will likely compromise the binding of many of these and additionally, the binding of antibodies under commercial development, however residual binding should provide protection from severe disease.Funding Information: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002) to D.I.S. and G.R.S. H.M.E.D. and J.Ren are supported by the Wellcome Trust (101122/Z/13/Z), D.I.S. and E.E.F. by the UKRI MRC (MR/N00065X/1). G.S and J.Z were supported by the Israel Science Foundation (grant no. 3814/19) and O.A and S.K (grant no. 3729/20) within the KillCorona—Curbing Coronavirus Research Program and by the Ben B. and Joyce E. Eisenberg Foundation. D.I.S. and G.R.S. are Jenner Investigators. This is a contribution from the UK Instruct-ERIC Centre. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). The computational aspects of this research were supported by the Wellcome Trust Core Award Grant Number 203141/Z/16/Z and the NIHR Oxford BRC. Declaration of Interests: G.R.S sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology. J.Z. and G.S. declare the Israel patent application no. 23/09/2020 – 277546 and U.S.A patent application no. 16/12/2020 - 63/125,984, entitled Methods and compositions for treating coronaviral infections.