DESAIN KANDIDAT VAKSIN CROSS-PROTECTIVE TERHADAP SARBECOVIRUS DAN MERBECOVIRUS: STUDI IN SILICO

• Main Author: Hosea Christiantono, Nicolas
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/57914
• Institution: Institut Teknologi Bandung

?-coronaviruses (?-CoVs), specifically the Merbecovirus and Sarbecovirus subgroups, have caused epidemics of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the pandemic Coronavirus Disease 2019 (COVID-19) in the last two decades. Both subgroups have natural hosts of bats that then undergo genetic mutation or recombination to be zoonotic and highly pathogenic. A vaccine is needed to provide cross-protection against Merbecovirus and Sarbecovirus since the potential for zoonotic transmission in ?-CoVs. Nucleocapsid (N) proteins are multifunctional, conserved, immunogenic, and enhance immune responses without triggering immunopathology. This study aims to construct a multi-peptide vaccine from the Merbecovirus and Sarbecovirus nucleocapsid protein consensus sequences. We obtained the 13 cytotoxic T lymphocyte (CTL) epitopes, 24 helper T (HTL) epitopes, and 11 linear B epitopes (LBL) with antigenicity greater than 0.4, sustainability score more than 0.4, and conserved more than 70% based on the SARS-CoV-2 and MERS-CoV reference sequences. Then, the vaccines were constructed from the immunodominant regions and linked to two types of adjuvants, namely B Subunit of Cholera Toxin (CTB) for the first construction (K1) and 50S ribosomal protein L7/L12 (RplL) for the second construction (K2), using rigid EAAAK linker and added PADRE sequences. The vaccine constructs were then predicted for their tri-dimensional structures, refined, and validated. Both vaccine structures have antigenicity in the range of 0.65, are hydrophilic, and do not adhere to the membrane. K1 has higher structural preservation (65%) and native nucleocapsid discontinuous epitope (30 a.a.) than K2 (46% and 15 a.a.). K2 has the best molecular interactions with Toll-like receptor (TLR) 2 and TLR4 because of its ability to recognize eight ligand-binding residues of TLR2 and 28 residues on TLR4. Thus, two multi-peptide vaccines from the Merbecovirus and Sarbecovirus N consensus sequences were successfully constructed and characterized by their physicochemical, structural, and interaction characteristics with TLRs. The predicted vaccine be able to provide cross-protection against the new coronavirus epidemic in the future.