In Silico Study of Variable Surface Proteins in Plasmodium Species: Perspectives in Drug Design

Yadav, Manoj Kumar; Swati, D.

doi:10.1007/s12539-015-0283-8

Cited by 3 publications

(4 citation statements)

References 31 publications

(29 reference statements)

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“…Moreover, in vitro, both hemozoin and soluble P. falciparum antigens (sPfAg) are capable of inducing BAFF release from monocytes and B‐cell co‐cultures . Within this context, it must be evoked that P. falciparum and P. vivax are genetically distant malaria parasites . Probably the heterogeneity between the two species, such as in its chemical composition of soluble antigens and hemozoin could differently modulate BAFF and APRIL production as well as cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…Within this context, it must be evoked that P. falciparum and P. vivax are genetically distant malaria parasites . Probably the heterogeneity between the two species, such as in its chemical composition of soluble antigens and hemozoin could differently modulate BAFF and APRIL production as well as cytokines. Indeed, our findings showed that, in P. vivax acute phase malaria, APRIL but not BAFF levels correlated positively with IL‐1, IL‐2, IL‐4, IL‐6, and IL‐13 levels.…”

Section: Discussionmentioning

confidence: 99%

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Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon

Pinna

Santos

Perce-da-Silva

et al. 2018

Immunity Inflam & Disease

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IntroductionA proliferation‐inducing ligand (APRIL) and B cell activation factor (BAFF) are known to play a significant role in the pathogenesis of several diseases, including BAFF in malaria. The aim of this study was to investigate whether APRIL and BAFF plasma concentrations could be part of inflammatory responses associated with P. vivax and P. falciparum malaria in patients from the Brazilian Amazon.MethodsBlood samples were obtained from P. vivax and P. falciparum malaria patients (n = 52) resident in Porto Velho before and 15 days after the beginning of treatment and from uninfected individuals (n = 12). We investigated APRIL and BAFF circulating levels and their association with parasitaemia, WBC counts, and cytokine/chemokine plasma levels. The expression levels of transmembrane activator and calcium‐modulating cyclophilin ligand interactor (TACI) on PBMC from a subset of 5 P. vivax‐infected patients were analyzed by flow cytometry.ResultsAPRIL plasma levels were transiently increased during acute P. vivax and P. falciparum infections whereas BAFF levels were only increased during acute P. falciparum malaria. Although P. vivax and P. falciparum malaria patients have similar cytokine profiles during infection, in P. vivax acute phase malaria, APRIL but not BAFF levels correlated positively with IL‐1, IL‐2, IL‐4, IL‐6, and IL‐13 levels. We did not find any association between P. vivax parasitaemia and APRIL levels, while an inverse correlation was found between P. falciparum parasitaemia and APRIL levels. The percentage of TACI positive CD4+ and CD8+ T cells were increased in the acute phase P. vivax malaria.ConclusionThese findings suggest that the APRIL and BAFF inductions reflect different host strategies for controlling infection with each malaria species.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon

Pinna

Santos

Perce-da-Silva

et al. 2018

Immunity Inflam & Disease

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“…The enzymes from both strains exhibited the optimal pH for enzyme catalysis, at pH 7.5, and were stable at temperatures below 60 degrees C. They therefore proposed that GSTs from both malarial strains are identical in their functional domain but different in level of gene expression (Harwaldt et al, 2002;Al-Qattan et al, 2016). Yadav MK et al analysed the possibility of using variable surface proteins as a common drug target in both the Plasmodium species (Yadav and Swati, 2016). Sequence analysis of variable surface proteins showed a low-level conservation within as well as between the species.…”

Section: Discussionmentioning

confidence: 99%

“…Structural alignment of variable surface proteins by superimposing them showed less conservation. The noted existence of structural differences showed that the variable surface proteins could not be used as a common drug target in both the malarial species (Yadav and Swati, 2016). The authors concluded that species-speci ic strategy may be followed for drug targeting against variable surface proteins of P. falciparum and P. vivax.…”

Section: Discussionmentioning

confidence: 99%

In silico characterization of human-malarial parasite species based on their DHFR and GST targets leading to a change in binding conformations of anti-malarial drugs

Sakpal¹,

Bastikar²,

Kothari³

et al. 2021

ijrps

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In this study, we mainly focused on three anti-malarial drugs which were analyzed against the two malarial targets. Chloroquine, Mefloquine and, Proguanil was chosen as anti-malarial drugs while DHFR and GST targets from human malarial parasites like Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax were considered for the study. This study was conducted to understand the sequence and structural similarity between protein DHFR and GST among four Plasmodium species as well as to find out there in silico interactions with above-stated drug candidates. There were many bioinformatics databases, tools, and software’s were run to bring out research. Our data showed not many structural differences between Plasmodium sequences but yet other characteristics of them that make them different from each other. Hence that variation has shown a difference in the binding patterns of drugs with target proteins.

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Characterization of Human-malarial Parasite Species based on DHFR and GST Targets Resulting in Changes in Anti-malarial Drug Binding Conformations

Sakpal

Kothari

Bastikar

2022

DMBL

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Background: In this study, we focused primarily on three anti-malarial drugs that were tested against two malarial targets. Anti-malarial drugs like chloroquine, mefloquine, proguanil were chosen, while DHFR and GST targets from human malaria parasites such as Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax were considered for the study. Objective: The purpose of this study was to determine the sequence and structural similarity of proteins DHFR and GST among four Plasmodium species as well as to discover in silico interactions with aforementioned drug candidates. Methods: To conduct research, many bioinformatics databases like PDB, UniProt, DrugBank, PubChem; tools, and software’s like Phyre 2.0, Clustal O (1.2.4), and AutoDock 4, AutoDock vina, Discovery studio visualizer were used to determine the evolutionary significance of Plasmodium species. Result: Hence that variation has shown a difference in the binding patterns of drugs with target proteins. Our findings revealed Plasmodium spp divergence or convergence as well as how structurally and sequentially they share similar or dissimilar features Conclusion: As a result of the diversity, variations in protein-drug binding patterns have emerged.

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In Silico Study of Variable Surface Proteins in Plasmodium Species: Perspectives in Drug Design

Cited by 3 publications

References 31 publications

Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon

Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon

In silico characterization of human-malarial parasite species based on their DHFR and GST targets leading to a change in binding conformations of anti-malarial drugs

Characterization of Human-malarial Parasite Species based on DHFR and GST Targets Resulting in Changes in Anti-malarial Drug Binding Conformations

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