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.