Page 80 - ITPS-7-1

INNOSC Theranostics and
Pharmacological Sciences PfHSP and polyamines interactions

deaths occur in Sub-Saharan Africa and high-risk areas a crucial need for new innovative, and effective antimalarial
such as South-east Asia, the Eastern Mediterranean, the drugs [3,4] . Newly developed drugs should at least be
Western Pacific, and the Americas . In 2019, the World able to terminate the parasite growth at any stage, in the
[1]
[6]
Health Organization (WHO) reported approximately 229 erythrocytic stage, mosquito stage, and human liver stage
million cases and 409,000 malarial deaths. Sub-Saharan as a way of changing the usual sequence of drug targets.
Africa accounted for 94% of these deaths . This parasitic Positively charged organic compounds with two or more
[2]
disease is transmitted to humans by female Anopheles amino groups found in cells of living organisms are referred
mosquitoes. Of more than 430 Anopheles species known to to as polyamines , and they play an important part in cell
[7]
exist, approximately 40 can transmit malaria. In humans, division and differentiation of P. falciparum [7,8] . These include
five Plasmodium species are causative agents of malaria diamine, putrescine, and triamine spermidine as well as
infection: Plasmodium falciparum, Plasmodium vivax, tetramine spermine, which are synthesized uniquely by the
Plasmodium ovale, Plasmodium malariae, and Plasmodium action of S-adenosylmethionine decarboxylase (AdometDC)
knowlesi. and ornithine decarboxylase (ODC) functioning as a single
P. falciparum is the most common malaria parasite as enzyme and spermidine synthase. The absence of spermine
it accounts for over 99% of malaria cases in Africa, 71.9% synthase, in P. falciparum, makes spermidine synthase
[8]
in the West Pacific region, 69% in the Mediterranean, and responsible for both spermidine and spermine synthesis .
62.8% in South-east Asia . The most vulnerable groups at The malaria parasite survives between the mosquito
[2]
risk of contracting malaria include pregnant women and host and the human host. During transmission between
children under the age of 5, with 67% of malaria death cases these two hosts, the parasite moves from a poikilothermic
being children under the age of 5 . Malaria mostly affects mosquito to a warm-blooded human, causing severe heat
[1]
developing tropical and subtropical countries. In these shock to the parasite. Thus, heat shock proteins (HSPs)
countries, outcomes of malaria include loss of education play a key role in the adaptation survival of the parasite
for children, and adults not being able to provide for their inside the human host . Heat shock proteins, which are
[9]
families due to physical and intellectual distress caused by a part of a large family of molecular chaperones, are well-
cerebral damage. The disease results in financial burdens known for their function in the refolding, maturation, and
for both the government and individuals. The WHO degradation of proteins . These are divided into small
[10]
reported that in Africa, direct costs of malaria sum up to heat shock proteins and major heat shock proteins [11,12] , of
approximately US$12 million annually, while households which the major ones have a molecular mass of >43 kDa,
spend a quarter of their income on treating malaria at home. and small heat shock proteins have molecular weights
[12]
The drug of choice for treating malaria is determined by of <43 kDa . Small heat shock proteins with molecular
several variables including age, the severity of the infection, weights of 15 – 43 kDa are called heat shock protein β and
baseline immunity, parasite sensitivity, and drug cost and are particularly known for their role in protecting cells
[13]
availability. In the early 1900s, quinine and its derivatives from stress .
were widely used to treat malaria . Many of these anti- 2. Materials and methods
[3]
malarial drugs are no longer in use due to P. falciparum and
P. vivax resistance against the drugs and undesirable side Supplementary S1 contains a list of online web servers
effects from compounds such as mepacrine [3,4] . However, used for bioinformatic analyses used in this study.
some quinine derivatives such as mefloquine are still in
use in combination with artesunate as binary combination 2.1. Sequence retrieval
drugs . At present, classes of drugs used for malaria Sequences of selected heat shock proteins from Pf3D7
[3]
include artemisinin, antifolates, 4-aminoquinolines, were retrieved from the PlasmoDB database. This database
8-aminoquinolines aryl-amino alcohols, and antibiotics. provides substantial Plasmodium spp. genome, proteome,
Artemisinin is the most widely used antimalarial drug and metabolome information. Genomic characteristics of
globally due to its efficacy against all forms of P. falciparum the selected heat shock proteins were obtained from the
strains by inhibiting the parasite’s phosphatidylinositol- National Centre of Biotechnological Information (NCBI)
3-kinase during the early ring stage with artemisinin database by selecting the gene ID of the selected HSP to
[5]
combination therapies being recommended to treat both identify the protein’s gene and chromosomal location.
complicated and uncomplicated P. falciparum malaria.
However, gene modification in the Plasmodium parasite 2.2. Multiple sequence alignment
results in resistance of the parasite to antimalaria drugs as Protein sequences of Hsp 20, Hsp 40, Hsp 60, Hsp 70-1,
the genes that encode target regions mutate, and this raises and Hsp 90 from Escherichia coli and Saccharomyces

Volume 7 Issue 1 (2024) 2 https://doi.org/10.36922/itps.1228