De novo design of anti-variant COVID-19 Vaccine

Abstract Recent studies highlight the effectiveness of hybrid SARS-CoV-2 vaccines combining wild-type nucleocapsid and Spike proteins. We have further enhanced this strategy by incorporating delta omicron variants’ spike protein mutations. Both mark shifts in viral transmissibility severity unvaccinated vaccinated patients. So their mutations are highly crucial for future variants also. Omicron is particularly adept at immune evasion mutating epitopes. The rapid adaptations sub to based simultaneous underline urgency new continuous battle against SARS-CoV-2. Therefore, we added three persistent T-cell stimulating peptides similar homologous sequences from seasonal Human Coronaviruses (HuCoV) an envelope peptide that elicits strong response. These clustered spike's cytoplasmic region with non-immunogenic linkers, enabling systematic arrangement. AlphaFold (Artificial intelligence-based model building) analysis suggests omitting transmembrane domain enhances these epitopes’ folding efficiency which can ensure immunity CD4+ structural Further molecular dynamics simulations validate compact conformation modeled structures a flexible C-terminus region. Overall, show stability less conformational fluctuation throughout simulation. Also, predicted epitopes maintained folds during simulation specificity response after vaccination. Our proposed approach may provide options diverse anti-viral peptides, HuCoV, into linker regions. This versatility be promising address outbreaks challenges posed various viruses effective management era innovative vaccines.