Bioinformatic analysis of Plasmodium knowlesi Serine Repeat Antigen 3 (SERA3) sequences for antimalarial peptide development.

Plasmodium knowlesi Serine Repeat Antigen 3 (PkSERA3) is an important protein that is expressed during late trophozoite and schizont stages of the parasite. The orthologue of PkSERA3 is P. falciparum SERA5 (PfSERA5) has a vital role in red blood cell membrane rupture and merozoite egress. Previous studies showed that peptide and drug-like inhibitors targeted PfSERA5 can inhibit parasite egress. However, there has been no study investigating antimalarial peptides based on PkSERA3. Therefore, the current study advances PkSERA3-targeted antimalarial drug discovery using bioinformatics tools and molecular docking. Our study focuses on the C-terminal region of PkSERA3. We compared Plasmodium SERAs, identified the conserved sequence, and designed the potential antimalarial peptides. These peptides were subjected to in silico screening to assess their toxicity and molecular docking studies. From Plasmodium SERAs alignment, we designed 8 peptides based on the amino acid sequence alignment. To increase cell membrane permeability, octa-arginine (rR8) was conjugated to the designed peptides. The lead peptides SE3P1-SE3P4 were docked to a PkSERA3 structural model with HPEPDOCK, yielding favourable docking scores from -135.07 to -179.42. In addition, most of the peptide has non-toxic and demonstrated minimal hemolytic activity toward human erythrocytes. This study identified potential therapeutic peptides using computational and theoretical approaches; however, experimental validation through in vitro enzymatic assay and P. knowlesi culture-based inhibition studies is essential to confirm their antimalarial potencies.