Success of Current COVID-19 Vaccine Strategies vs. the Epitope Topology of SARS-CoV-2 Spike Protein-Receptor Binding Domain (RBD): A Computational Study of RBD Topology to Guide Future Vaccine Design.

Coronavirus disease-2019 (COVID-19) is a pandemic with a high morbidity rate occurring
over recent years. COVID-19 is caused by the severe acute respiratory syndrome causing coronavirus
type-2 (SARS-CoV-2). COVID-19 not only challenged mankind but also gave scope to the evolution
of various vaccine design technologies. Although these vaccines protected and saved many lives,
with the emerging viral strains, some of the strains may pose a threat to the currently existing
vaccine design that is primarily based on the wild type spike protein of SARS-CoV-2. To evaluate
the risk involved from such mutant viral strains, we performed a systematic in silico amino acid
substitution of critical residues in the receptor binding domain (RBD) of the spike protein. Our
molecular modeling analysis revealed significant topological changes in the RBD of spike protein
suggesting that they could potentially contribute to the loss of antigen specificity for the currently
existing therapeutic antibodies/vaccines, thus posing a challenge to the current vaccine strategies
that are based on wild type viral spike protein epitopes. The structural deviations discussed in this
article should be considered carefully in the future vaccine design.