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.