Discussion
The newly emerging mutant RBDs may affect the affinity for the viral
receptor. In addition, such mutations at the virus-receptor interaction
face may alter the ability of RBD-specific antibodies - induced by
previous infection - to neutralize the mutant viruses. A previous study
showed that serum neutralization is not compromised by N501Y (found in
the strain B.1.1.7) 10. In contrast, E484K (found in
B.1.1.7 and in P.1 strains) was associated with reduced neutralization11,12. Interestingly, studies applying in vitropressure produced similar mutations as those that occurred naturally13. When we investigated whether distinct mutations
may affect receptor affinity we found that N501Y mutation enhanced
affinity for the viral receptor ACE2 both as a single mutation as well
as in the triple mutation, while E484K mutation alone did not affect the
interaction with ACE2 .
In addition, such mutations at the virus-receptor interaction interface
may alter the ability of RBD-specific antibodies to recognize and
neutralize the mutant variants. A previous study showed that serum
neutralization is not compromised by N501Y (also found in the strain
B.1.1.7) 10 14. In contrast, E484K
(found B.1.1.7 and in P.1 strains) was associated with reduced
neutralization 11,12. Interestingly, studies applyingin vitro pressure produced similar mutations as those that
occurred naturally 13. In this study we showed that
convalescent sera has reduced ability to recognize
RDBTRIP variants explaining why the mutant SARS-CoV-2
strain P.1 is more infectious 15 and less susceptible
to neutralization by antibodies induced with RBDWT.
In summary, our data demonstrate that distinct mutations may affect
receptor affinity which likely affects viral infectivity versus
recognition by convalescent sera which likely affects neutralization.
These observations may shed light on the potential origin of the viral
mutants. The variant with the mutation N501Y shows enhanced affinity but
almost normal recognition by convalescent antibodies. This indicates
that this variant spread largely by increased infectivity while
recognition by antibodies of previously infected individuals was less
relevant, a phenotype consistent with the epidemiology in the UK, where
overall infection rates remain relatively low, rendering the previously
infected individuals a relatively unimportant source of viral spread16. In contrast, the triple mutant variant shows
enhanced infectivity and escape from antibody-recognition. It may
therefore not be a coincidence that this variant originated in Manaus, a
region in Brazil previously seen to have seroprevalence of
>80%, forcing the virus to escape immunity for further
spreading 17.