Keywords
SARS-CoV-2, RBD, affinity, neutralization, ACE2, biolayer interferometry
Introduction
SARS-CoV-2 has caused a pandemic that is characterized in many countries by several waves of infection 1 2. While the origin of these infection waves may differ in different regions of the world, the latest increase seen in numbers of infected individual is apparently caused by the occurrence of mutated viral strains 3. The most prominent mutated strains are following variants: B.1.1.7. (N501Y, D614G), P.1 (K417N/T, E484K, N501Y) and B.1.351 (K417N, E484K, N501Y, D614G) 4, which show mutations in the receptor binding domain (RBD) and receptor binding motif (RBM) of the spike (S) glycoprotein. RBD and in particular RBM are responsible for interaction with the cellular receptor ACE2 and are the primary target of neutralizing antibodies 5 (Fig.1). Mutant viruses may spread more efficiently because they show increased affinity for the receptor or because they escape neutralizing antibody responses. The importance of receptor affinity has been illustrated by SARS-CoV-1, which showed a 4-fold lower affinity for ACE2 and also was much less contagious and showed strongly reduced transmission compared to SARS-CoV-2 6.
Viruses that escape neutralization are typically called serotypes and usually may only occur when a large proportion of individuals show antibody-based immunity against the original strain and further spread may only be possible by escape of neutralizing antibody responses7. For SARS-CoV-2, this is certainly not the case on a global scale but certain regions of the world may show infections rates that are compatible with serotype formation.
Here we assessed the molecular basis for antibody escape and how the RBD mutations present in two variants of concern (B.1.1.7 and P.1) influence the affinity to the receptor.