Plasmodium killing and antimicrobial lineal or cyclic-peptides computationally targeted the circumsporozoite CSP protein

The RT39 amphipathic lineal-peptide (ALP), described as the faster membranolytic-killer of circumsporozoite Plasmodium falciparum (Aguirre-Botero et al, 2024), computationally predicted the highest affinities to the external circumsporozoite protein (CSP), compared to other described ALPs. Additional computational co-cyclizations of CSP/ALPs generated CSP/cycRT39 cyclic-conformers predicting the highest picoMolar affinities to target CSP-TSR domains with de novo alternative amino acid sequences, proteolytic resistance, and chemical stability. A preliminary co-screening of Uniprot antimicrobial peptides (AMPs), discovered some CSP/cycAMP-conformers predicting similar high affinities. These novel cycALP and/or cycAMP amino acid sequences may deserve experimental validation tests. Could some of them help to advance on circumsporozoite interference in mosquitos and/or humans?.