AccScience Publishing / ITPS / Volume 7 / Issue 1 / DOI: 10.36922/itps.1228
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ORIGINAL RESEARCH ARTICLE

In silico evaluation of heat shock proteins reveals an interplay with polyamines as a survival strategy for the Plasmodium falciparum

Godlo Sesethu1 ,  Maxam Nombalentle1 ,  Mthembu Yamkela1 ,  Mpumza Anelisa1 ,  Stanley Makumire2,3 ,  Noxolo Mkwetshana1 ,  Krishna K. Govender4 ,  Xolani H. Makhoba5*
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1 Department of Microbiology and Biochemistry, University of Fort Hare, Alice Campus, South Africa
2 Structural Biology Research Unit, Department of Integrative Biomedical Sciences, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa
3 Protein and Structural Biology Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7A, 90220 Oulu, Finland
4 Department of Chemical Sciences, University of Johannesburg, P. O. Box 17011, Doornfontein Campus, 2028, Johannesburg, South Africa
5 Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Turfloop Campus, Sovenga, South Africa
INNOSC Theranostics and Pharmacological Sciences 2024, 7(1), 1228 https://doi.org/10.36922/itps.1228
Submitted: 3 July 2023 | Accepted: 15 August 2023 | Published: 13 September 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

The current drugs available in the market are not effective due to growing numbers of resistance to the causative agent of malaria. There are various Plasmodium parasites, of which Plasmodium falciparum is the main cause of morbidity and mortality reported worldwide. Therefore, there is an urgent need to come up with an innovative and effective treatment for this disease. Polyamines play a major role in the parasite’s well-being and growth, while heat shock proteins keep the proteomics of the parasite in good shape. In this study, an in silico analysis of the interaction between putrescine, spermidine, spermine, and heat shock proteins was carried out to establish the binding site for drug discovery. Computational tools such as Bioedit, PROCHECK, KNIME Hub, and Schrodinger were used. The results revealed interactions between polyamines and heat shock proteins with glutamine and aspartic acid being common amino acids where interaction occurs between the chaperones and polyamines. Molecular dynamics showed a strong interaction between PfHsp70-1 and putrescine, but the best interaction is observed for PfHsp70-1 and spermidine. Based on these results, a follow-up study will be conducted to establish the synthesis of drugs that will be used as targets for both polyamines and heat shock proteins to eradicate malaria.

Keywords
Malaria
In silico
Putrescine
Spermidine
Spermine
Heat shock proteins
Multi-drug development
Funding
University of Fort Hare SEED grants
SAMRC-Self-Initiated Research grants
Conflict of interest
The authors declare no conflicts of interest.
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Print ISSN: 2705-0734, Published by AccScience Publishing
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