Characterization of sulfated polysaccharide activity against virulent Plasmodium falciparum PHISTb/RLP1 protein

• DOI: 10.12688/f1000research.26756.2
• Publication Date: 2022-04-29T14:33:15Z
• Authors: Jennifer M. Mutisya; Victor A. Mobegi; Johnson K. Kinyua; Martha N. Kivecu; Raphael O. Okoth; Gladys C. Chemwor; Edwin W. Mwakio; Agnes C. Cheruiyot; Redempta A. Yeda; Charles O. Okello; Jackline A. Juma; Benjamin H. Opot; Dennis W. Juma; Amanda L. Roth; Hosea M. Akala; Ben M. Andagalu
• Keywords: Ramachandran plot; Sanger sequencing

<ns5:p><ns5:bold>Background: </ns5:bold>The emergence of artemisinin resistance in South East Asia calls for urgent discovery new drug compounds that have antiplasmodial activity. Unlike the classical compound screening methods, rational approach involving targeted is less cumbersome and therefore key innovation compounds. <ns5:italic>Plasmodium falciparum</ns5:italic> (Pf) utilizes process host erythrocyte remodeling using Plasmodium-helical interspersed sub-telomeric domain (PHIST) containing proteins, which are amenable targets. The aim this study to identify inhibitors PHIST from sulfated polysaccharides as antimalarials.</ns5:p><ns5:p> <ns5:bold>Methods: </ns5:bold>251 samples an ongoing epidemiology malaria sensitivity patterns Kenya were sequenced PHISTb/RLP1 gene Sanger sequencing. reads mapped reference Pf3D7 protein sequence CLC Main Workbench. Homology modeling both mutant structures was achieved LOMETs tool. models refined ModRefiner energy minimization. Ramachandran plot generated by ProCheck assess conformation amino acids model. Protein binding sites predictions assessed FT SITE software. We searched prospective antimalarials PubChem. Docking experiments AutoDock Vina analysis results visualized PyMOL.</ns5:p><ns5:p> <ns5:bold>Results: </ns5:bold>Sanger sequencing 86 complete sequences. Upon mapping sequences reference, 12 non-synonymous single nucleotide polymorphisms considered structure analysis. Eleven with activity identified. Both modeled had a score &gt;90% favored region. Ten interacted acid residues PHISTb RESA domains, showing potential against these proteins.</ns5:p><ns5:p> <ns5:bold>Conclusion: </ns5:bold>This research identifies exported proteins can be used <ns5:italic>in vitro </ns5:italic>tests <ns5:italic>Plasmodium</ns5:italic> parasite.</ns5:p>