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bioRxiv · 10.1101/2025.09.30.679691

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

Coll, J.
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Abstract

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?. O_FIG O_LINKSMALLFIG WIDTH=147 HEIGHT=200 SRC="FIGDIR/small/679691v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@894c28org.highwire.dtl.DTLVardef@1e70fd0org.highwire.dtl.DTLVardef@bf448aorg.highwire.dtl.DTLVardef@12ce348_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Coll, J.. 2025-10-01. Plasmodium killing and antimicrobial lineal or cyclic-peptides computationally targeted the circumsporozoite CSP protein. https://doi.org/10.1101/2025.09.30.679691

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