Inhibition of Plasmodium falciparum cysteine proteases by the sugarcane cystatin CaneCPI-4

Melo, Pollyana M.S.; Maluf, Sarah El Chamy; Azevedo, Mauro Ferreira de; Paschoalin, Thaysa; Budu, Alexandre; Bagnaresi, Piero; Henrique-Silva, Flávio; Soares-Costa, Andréa; Gazarini, Marcos L.; Carmona, Adriana K.

doi:10.1016/j.parint.2017.12.005

Cited by 19 publications

(9 citation statements)

References 18 publications

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“…Cystatins inhibited the growth of Porphyromonas gingivalis [117][118][119] and Staphylococcus aureus [120]. Cysteine proteinase inhibitors have also been reported as inhibitors of parasite infections such as malaria [121]. Cystatins also exhibit antifungal activity.…”

Section: Antimicrobial Activitymentioning

confidence: 99%

Egg White Cystatin – A Review

et al. 2020

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Hen eggs are widely used, not only for human consumption, but also as an important material in food production and in pharmaceutical and cosmetics industry. Cystatin is a biologically active component of egg white, mostly used as an inhibitor of papain-like cysteine proteases. It was isolated from chicken egg white and has later been used in the nomenclature of structurally and functionally related proteins. Cystatins from animals, including mouse, rat, dog, cow and chicken egg white have been isolated and recently used in foodstuffs and drug administration. Cystatin has found its place and use in medicine due to its antimicrobial, antiviral and insecticidal effects, for the prevention of cerebral hemorrhage and control of cancer cell metastasis.

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Section: Antimicrobial Activitymentioning

confidence: 99%

Egg White Cystatin – A Review

et al. 2020

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“…Among them, only eight compounds showed potential binding affinity to the target CPs active sites, while compound 117 extracted from Millettia usaramensis showed the maximum efficiency [149] . Recently, a cystatin from sugarcane (Cane CPI-4), exhibited in vitro inhibitory potency against P. falciparum infected erythrocytes and recombinant FPs 2 and 3, and it decreased hemozoin formation and parasitemia [150] .…”

Section: Dual Actionmentioning

confidence: 99%

Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part III: Protozoa (2): Plasmodium spp.

Abaza

2019

Parasitologists United Journal

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“…The inflation of malarial parasite inside the infected red blood cell is proportionate to the rate of its food assimilation ( Goldberg et al, 1990 ). Cysteine proteases of Plasmodium are implicated with several biological processes such as rupture of membranes, degradation of Hb, protein trafficking, and host cell invasion ( Lehmann et al, 2014 ; Melo et al, 2018 ). Thus, the growth of malarial parasites is measured by the interference of key indicator protein FP2 ( Liu et al, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

Target-Based Virtual Screening of Natural Compounds Identifies a Potent Antimalarial With Selective Falcipain-2 Inhibitory Activity

et al. 2022

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We employed a comprehensive approach of target-based virtual high-throughput screening to find potential hits from the ZINC database of natural compounds against cysteine proteases falcipain-2 and falcipain-3 (FP2 and FP3). Molecular docking studies showed the initial hits showing high binding affinity and specificity toward FP2 were selected. Furthermore, the enzyme inhibition and surface plasmon resonance assays were performed which resulted in a compound ZINC12900664 (ST72) with potent inhibitory effects on purified FP2. ST72 exhibited strong growth inhibition of chloroquine-sensitive (3D7; EC50 = 2.8 µM) and chloroquine-resistant (RKL-9; EC50 = 6.7 µM) strains of Plasmodium falciparum. Stage-specific inhibition assays revealed a delayed and growth defect during parasite growth and development in parasites treated with ST72. Furthermore, ST72 significantly reduced parasite load and increased host survival in a murine model infected with Plasmodium berghei ANKA. No Evans blue staining in ST72 treatment indicated that ST72 mediated protection of blood–brain barrier integrity in mice infected with P. berghei. ST72 did not show any significant hemolysis or cytotoxicity against human HepG2 cells suggesting a good safety profile. Importantly, ST72 with CQ resulted in improved growth inhibitory activity than individual drugs in both in vitro and in vivo studies.

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Inhibition of Plasmodium falciparum cysteine proteases by the sugarcane cystatin CaneCPI-4

Cited by 19 publications

References 18 publications

Egg White Cystatin – A Review

Egg White Cystatin – A Review

Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part III: Protozoa (2): Plasmodium spp.

Target-Based Virtual Screening of Natural Compounds Identifies a Potent Antimalarial With Selective Falcipain-2 Inhibitory Activity

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