Systems biology and bioinformatics approaches in leishmaniasis

Rajkhowa, Sanchaita; Hazarika, Zaved; Jha, Anupam Nath

doi:10.1016/b978-0-12-821100-7.00018-2

Cited by 9 publications

(4 citation statements)

References 201 publications

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“…The pathway of ergosterol biosynthesis, the main sterol of fungi, Leishmania spp, and Trypanosoma cruzi is the target of the most important antifungal and antileishmanial drugs. [ 27 ] Among them, allylamines and azoles drug families such as terbinafine which inhibits squalene epoxidase, and ketoconazole that inhibits C14-demethylase (CYP51), are the most interested leishmanicidal agents. [ 28 29 ] drug combination therapy has attracted the researcher's attention to reach a synergic effect on the disease, through herbal medicines.…”

Section: Discussionmentioning

confidence: 99%

In Vitro study of the leishmanicidal activity of perovskia abrotanoides terpenoid-rich fractions against Leishmania major (MRHO/IR/75/ER)

Sebghatollahi,

Sadeghi Dinani,

Emarati Noushabadi

et al. 2023

Adv Biomed Res

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Background: Cutaneous leishmaniasis (CL) is an ulcerative skin disease caused by some species of the genus Leishmania . Evidence shows that Perovskia abrotanoides is an important herbal medicine against Leishmania . This study was conducted to investigate the killing effect of terpenoid-rich fractions on promastigotes of L. major (MRHO/IR/75/ER). Material and Method: The eluates of reverse phased medium pressure liquid chromatography (RP-MPLC) of the extract were subjected to thin-layer chromatography (TLC) and categorized into six final fractions. Primary proton nuclear magnetic resonance (H-NMR) spectroscopy confirmed fractions' nature. Fractions 4, 5, and 6 (F4, F5, F6) were identified as terpenoid-rich content. Two concentrations of 50 and 100 μg/ml were prepared to test leishmanicidal activity. Followed by treating promastigotes of L. major by the fractions in incubation times of 12, 24, and 48 hours, their viability was determined using a cell proliferation MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Result: F4, F5, and F6 showed significant killing activity on promastigotes of L. major in a concentration-dependent manner. The viability of promastigotes was significantly reduced at a concentration of 100 μg/ml compared to 50 μg/ml (P-value <0.05). Also, over time a significant decreasing trend in the viability of promastigotes confirmed the time-dependent manner of the fractions (P-value <0.01). Furthermore, F5 had the highest leishmanicidal activity at the first incubation time compared with other fractions. Conclusion: Terpenoid-rich fractions of the P. abrotanoides have a leishmanicidal activity that depends on time and concentration. Among them, F5 has the highest potency that may contain potent terpenoid constituents.

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Section: Discussionmentioning

confidence: 99%

In Vitro study of the leishmanicidal activity of perovskia abrotanoides terpenoid-rich fractions against Leishmania major (MRHO/IR/75/ER)

Sebghatollahi,

Sadeghi Dinani,

Emarati Noushabadi

et al. 2023

Adv Biomed Res

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“…Drug-target networks, drug-drug networks, drug-disease networks, and protein interaction networks have all been shown to be effective in identifying new options for drug development or repositioning in previous research. In the human protein-protein interaction network, the network-based approach combines a system-pharmacology-based network medicine framework that analyzes the interaction between the virus-host interactome and therapeutic targets [68,69].…”

Section: Procedures Based On Pathways or Networkmentioning

confidence: 99%

A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

Khataniar

Pathak

Rajkhowa

et al. 2022

COVID

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Drug repurposing is a more inexpensive and shorter approach than the traditional drug discovery and development process. The concept of identifying a potent molecule from a library of pre-existing molecules or an already approved drug has become a go-to tactic to accelerate the identification of drugs that can prevent COVID-19. This seemingly uncontrollable disease is caused by SARS-CoV-2. It is a novel virus of the Betacoronavirus genus, exhibiting similarities to the previously reported SAR-CoV genome structure and viral pathogenesis. The emergence of SARS-CoV-2 and the rapid outbreak of COVID-19 have resulted in a global pandemic. Researchers are hard-pressed to develop new drugs for total containment of the disease, thus making the cost-effective drug repurposing a much more feasible approach. Therefore, the current review attempts to collate both the experimental and computational drug repurposing strategies that have been utilized against significant drug targets of SARS-CoV-2. Along with the strategies, the available druggable targets shall also be discussed. However, the occurrence of frequent recombination of the viral genome and time-bound primary analysis, resulting in insignificant data, are two major challenges that drug repurposing still faces.

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“…Severe effects on these organs may even lead to death. 6,7 Although there are approved medications for the treatment of VL, including pentavalent antimonials, amphotericin B, miltefosine, and paromomycin, these medications may cause adverse side effects, and drug resistance has emerged. Therefore, there is a need for new antileishmanial drugs with better efficacy and fewer side effects.…”

Section: Introductionmentioning

confidence: 99%

“…In humans, VL affects visceral organs such as the liver and spleen. Severe effects on these organs may even lead to death 6,7 …”

Section: Introductionmentioning

confidence: 99%

Computational multi‐target approach to target essential enzymes of Leishmania donovani using comparative molecular dynamic simulations and MMPBSA analysis

Saha

Jha

2023

Phytochemical Analysis

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IntroductionVisceral leishmaniasis (VL) is caused by Leishmania donovani. The purine and pyrimidine pathways are essential for L. donovani. Simultaneously inhibiting multiple targets could be an effective strategy to eliminate the pathogen and treat VL.ObjectiveWe aimed to target the essential enzymes of L. donovani and inhibit them using a multi‐target approach.Materials and methodsA systematic analytical method was followed, in which first reported inhibitors of two essential enzymes (adenine phosphoribosyl‐transferase [APRT] and dihydroorotate dehydrogenase [DHODH]) were collected and then ADMET and PASS analyses were conducted using the Lipinski rule and Veber's rule. Additionally, molecular docking between screened ligands and proteins were performed. The stability of complexes was analyzed using molecular dynamics (MD) simulations and MMPBSA analysis.ResultsInitially, 6,220 unique molecules were collected from the PubChem database, and then the Lipinski rule and Veber's rule were used for screening. In total, 203 compounds passed the ADMET test; their antileishmanial properties were tested by PASS analysis. As a result, 15 ligands were identified. Molecular docking simulations between APRT or DHODH and these 15 ligands were performed. Four molecules were found to be plant‐derived compounds. Lig_2 and Lig_3 had good docking scores with both proteins. MD simulations were performed to determine the dynamic behavior and binding patterns of complexes. Both MD simulations and MMPBSA analysis showed Lig_3 is a promising antileishmanial inhibitor of both targets.ConclusionPromising plant‐derived compounds that might be used to combat VL were obtained through a multi‐target approach.

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Systems biology and bioinformatics approaches in leishmaniasis

Cited by 9 publications

References 201 publications

In Vitro study of the leishmanicidal activity of perovskia abrotanoides terpenoid-rich fractions against Leishmania major (MRHO/IR/75/ER)

In Vitro study of the leishmanicidal activity of perovskia abrotanoides terpenoid-rich fractions against Leishmania major (MRHO/IR/75/ER)

A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

Computational multi‐target approach to target essential enzymes of Leishmania donovani using comparative molecular dynamic simulations and MMPBSA analysis

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