Abstract
Fifty ~20-amino acid (aa)-long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus’ main genetic variants for complementary trial C-21 . Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPII L ) formation, replacing β-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPII L propensity formation. All these modified structures had PPII L formation propensity to enable target peptide interaction with human leukocyte antigen-DRβ1* (HLA-DRβ1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRβ1* molecules), predicted to cover 77.5% to 83.1% of the world’s population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.
Keywords: SARS-CoV-2; modified synthetic peptides; multiepitope; mutational variants; supramutational; worldwide coverage.
【저자키워드】 SARS-CoV-2, mutational variants, multiepitope, modified synthetic peptides, supramutational, worldwide coverage., 【초록키워드】 Structure, Vaccine development, immune response, pandemic, Trial, Neutralising Antibodies, polymorphism, human leukocyte antigen, peptide, virus, E protein, DNA, Coverage, neutralising antibody, peptides, genetic variability, Genetic variant, mutant, methodology, molecular, Antigen presentation, synthetic peptides, Antibody titre, Amino acid, Interaction, complementary, major histocompatibility complex, leukocyte, residues, SARS-CoV-2 S, backbone, Specific, MHCII, approach, selected, predicted, induce, genotyped, parental, concerning, histocompatibility complex, disrupting, replacing, physicochemical, synthesised, vaccine for COVID-19, π-π interaction, 【제목키워드】 Population, synthetic, Covering,