Introduction: The ongoing coronavirus disease 2019 (COVID-19), which emerged in December 2019, is... more Introduction: The ongoing coronavirus disease 2019 (COVID-19), which emerged in December 2019, is a serious health concern throughout the world. Despite massive COVID-19 vaccination on a global scale, there is a rising need to develop more effective vaccines and drugs to curb the spread of coronavirus. Methodology: In this study, we screened the amino acid sequence of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 (the causative agent of COVID-19) for the identification of B and T cell epitopes using various immunoinformatic tools. These identified potent B and T cell epitopes with high antigenicity scores were linked together to design the multi-epitope vaccine construct. The physicochemical properties, overall quality, and stability of the designed vaccine construct were confirmed by suitable bioinformatic tools. Results: After proper in silico prediction and screening, we identified 3 B cell, 18 CTL, and 10 HTL epitopes from the RdRp protein sequence. The screened epitopes...
BackgroundRheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which mainly affe... more BackgroundRheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which mainly affects small joints, occurs most commonly in middle‐aged adults, and can be fatal in severe cases. The exact etiology of RA remains unknown. However, uncontrolled expression of pro‐inflammatory cytokines and chemokines can contribute to the pathogenesis of RA.AimIn the current study, we assessed the potential of serum concentrations of interleukin (IL)‐1β, IL‐6, tumor necrosis factor (TNF)‐α, IL‐8, and C‐C motif chemokine ligand (CCL)5 as early predictive markers for RA.MethodsIn addition to clinical examination, blood samples were collected from 100 Saudi patients recently diagnosed with early RA for basic and serological tests, including rheumatoid factor (RF), C‐reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Sera of 32 healthy individuals were used as controls. Specific enzyme‐linked immunosorbent assay was used to quantify the serum IL‐1β, IL‐6, TNF‐α, IL‐8, and CCL5 ...
Abbreviations DNA Deoxyribonucleic acid dNTP Deoxyribonucleotide triphosphate E. coli Escherichia... more Abbreviations DNA Deoxyribonucleic acid dNTP Deoxyribonucleotide triphosphate E. coli Escherichia coli FLA Free-living amoebae ITS Internal transcribed spacers KCl Magnesium chloride LB Luria-Bertini MgCl 2 Magnesium chloride NNA Non-nutrient agar PAM Primary amoebic meningoencephalitis PCR Polymerase chain reaction Abstract. Naegleria is well recognized for primary amoebic meningoencephalitis which always results into death. To date there is not a single report demonstrating molecular identification of Naegleria from water resources of Pakistan thus the aim of the proposed study. Here, in total 135 various water samples (like domestic tap water, municipal water, sea water, well water, tube well water, canal water, boring water, sewage water, lake water and stream water) were collected across Pakistan and evaluated for Naegleria species. Naegleria australiensis (pathogenic) and Naegleria lovaniensis (non pathogenic) were isolated on non nutrient agar plates and were further identifi...
Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found ... more Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found effective against an array of pathogens including fungi, bacteria, viruses, and protozoa. Here, we evaluated its antileishmanial activity and possible mechanism of action through different in vitro and in silico experiments. It inhibited the growth and proliferation of the parasites significantly with a IC50 value of 1.019 ± 0.116 mM in vitro. It also reduced the growth of intra-macrophagic amastigotes with a IC50 value of 0.2858 ± 0.01398 mM. It induced the reactive oxygen species (ROS) in parasites in a dose-dependent manner. Through 2,7-dichloro dihydro fluorescein diacetate (H2DCFDA) staining, it was observed that around 96.9% parasites were ROS positive at 2.0 mM concentration of hesperidin. The ROS generated led to the apoptosis of parasites in a dose-dependent manner as observed by annexin/PI staining. Molecular docking with one of the very important and unique drug-targets of Lei...
Shannon’s information theoretic perspective of communication helps one to understand the storage ... more Shannon’s information theoretic perspective of communication helps one to understand the storage and processing of information in one-dimensional sequences. An information theoretic analysis of 937 available completely sequenced prokaryotic genomes and 238 eukaryotic chromosomes is presented. Information content (Id) values were used to cluster these chromosomes. Chargaff’s second parity rule i.e compositional self-complementarity, an empirical fact is observed in all the genomes, except for the proteobacteria Candidatus Hodgkinia cicadicola. High information content, arising out of biased base composition in all the 14 chromosomes of Plasmodium falciparum is found among two other genomes of prokaryotes viz. Buchnera aphidicola str. Cc (Cinara cedri) and Candidatus Carsonella ruddii PV. Despite size and compositional variations, both prokaryotic and eukaryotic genomes do not deviate significantly from an equiprobable and random situation. Eukaryotic chromosomes of an organism tend t...
We report a 60-year-old Saudi patient with the clinical diagnosis of Alzheimer`s disease (AD) and... more We report a 60-year-old Saudi patient with the clinical diagnosis of Alzheimer`s disease (AD) and a novel mutation in the presenilin gene. We investigated mutations in the presenilin-1 gene in Saudi patients with AD using polymerase chain reaction and direct DNA sequencing methods. We extracted genomic DNA from the whole blood of both patients and normal control individuals. We sequenced and compared amplicons with the sequences of the respective exons of normal individuals as well as data available in GenBank. We detected a homozygous mutation (g-c) in exon 12, resulting in the missense mutation (Arg377Thr), in the DNA of a 60-year-old patient. We located this mutation in the cytoplasmic loop near the transmembrane domain 7.
Chalcones are secondary metabolites belonging to the flavonoid (C6-C3-C6 system) family that are ... more Chalcones are secondary metabolites belonging to the flavonoid (C6-C3-C6 system) family that are ubiquitous in edible and medicinal plants, and they are bioprecursors of plant flavonoids. Chalcones and their natural derivatives are important intermediates of the flavonoid biosynthetic pathway. Plants containing chalcones have been used in traditional medicines since antiquity. Chalcones are basically α,β-unsaturated ketones that exert great diversity in pharmacological activities such as antioxidant, anticancer, antimicrobial, antiviral, antitubercular, antiplasmodial, antileishmanial, immunosuppressive, anti-inflammatory, and so on. This review provides an insight into the chemistry, biosynthesis, and occurrence of chalcones from natural sources, particularly dietary and medicinal plants. Furthermore, the pharmacological, pharmacokinetics, and toxicological aspects of naturally occurring chalcone derivatives are also discussed herein. In view of having tremendous pharmacological po...
Leishmaniasis is a vector-borne disease caused by around 20 species of Leishmania. The main clini... more Leishmaniasis is a vector-borne disease caused by around 20 species of Leishmania. The main clinical forms of leishmaniasis are cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). VL is caused by Leishmania infantum in Central and South America, Mediterranean Basin, Middle East, and by L. donovani in Asia and Africa. Sterol C-24 methyltransferase (LdSMT) of L. donovani is a transferase enzyme of the sterol biosynthesis pathway. This pathway is one of the major targets for drug developments in Leishmania. Due to insufficient evidence about the exact function of SMT inside the cell and the uniqueness of the SMT enzyme in the Leishmania parasites made it a significant target for an effective drug development approach. We performed virtual screening of the Food and Drug Administration (FDA)-approved drug library against LdSMT and found simeprevir, an antiviral drug on top in the binding score. It showed a significant binding affinity with LdSMT. The binding was supported by hydrogen bonds and several other interactions. Simeprevir inhibited L. donovani growth of promastigotes with 50% inhibitory concentration (IC50 ) of 51.49 ± 5.87 μM. Further studies showed that simeprevir induced ROS generation in 44.7% of parasites at 125-μM concentration. Here, we for the first time reported simeprevir as an antileishmanial lead molecule using a drug repurposing approach.
Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activiti... more Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activities. Here, we evaluated its antileishmanial properties and its mechanism of action through different in silico and in vitro assays. Cynaroside exhibited antileishmanial activity in time- and dose-dependent manner with 50% of inhibitory concentration (IC50) value of 49.49 ± 3.515 µM in vitro. It inhibited the growth of parasite significantly at only 20 µM concentration when used in combination with miltefosine, a standard drug which has very high toxicity. It also inhibited the intra-macrophagic parasite significantly at low doses when used in combination with miltefosine. It showed less toxicity than the existing antileishmanial drug, miltefosine at similar doses. Propidium iodide staining showed that cynaroside inhibited the parasites in G0/G1 phase of cell cycle. 2,7-dichloro dihydro fluorescein diacetate (H2DCFDA) staining showed cynaroside induced antileishmanial activity through reac...
Leishmaniasis is a neglected tropical disease caused by trypanosomatid parasite belonging to the ... more Leishmaniasis is a neglected tropical disease caused by trypanosomatid parasite belonging to the genera Leishmania. Leishmaniasis is transmitted from one human to other through the bite of sandflies. It is endemic in around 98 countries including tropical and subtropical regions of Asia, Africa, Southern America, and the Mediterranean region. Sterol C‐24 methyltransferase (LdSMT) of Leishmania donovani (L. donovani) mediates the transfer of CH3‐group from S‐adenosyl methionine to C‐24 position of sterol side chain which makes the ergosterol different from cholesterol. Absence of ortholog in human made it potential druggable target. Here, we performed virtual screening of library of natural compounds against LdSMT to identify the potential inhibitor for it and to fight leishmaniasis. Gigantol, flavan‐3‐ol, and parthenolide showed the best binding affinity towards LdSMT. Further, based on absorption, distribution, metabolism, and excretion properties and biological activity prediction, gigantol showed the best lead‐likeness and drug‐likeness properties. Therefore, we further elucidated its antileishmanial properties. We found that gigantol inhibited the growth and proliferation of promastigotes as well as intra‐macrophagic amastigotes. Gigantol exerted its antileishmanial action through the induction of reactive oxygen species in dose‐dependent manner. Our study, suggested the possible use of gigantol as antileishmanial drug after further validations to overcome leishmaniasis.
The coronavirus disease 2019 (COVID-19), which emerged in December 2019, continues to be a seriou... more The coronavirus disease 2019 (COVID-19), which emerged in December 2019, continues to be a serious health concern worldwide. There is an urgent need to develop effective drugs and vaccines to control the spread of this disease. In the current study, the main phytochemical compounds of Nigella sativa were screened for their binding affinity for the active site of the RNA-dependent RNA polymerase (RdRp) enzyme of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The binding affinity was investigated using molecular docking methods, and the interaction of phytochemicals with the RdRp active site was analyzed and visualized using suitable software. Out of the nine phytochemicals of N. sativa screened in this study, a significant docking score was observed for four compounds, namely α-hederin, dithymoquinone, nigellicine, and nigellidine. Based on the findings of our study, we report that α-hederin, which was found to possess the lowest binding energy (–8.6 kcal/mol) and hence the best binding affinity, is the best inhibitor of RdRp of SARS-CoV-2, among all the compounds screened here. Our results prove that the top four potential phytochemical molecules of N. sativa, especially α-hederin, could be considered for ongoing drug development strategies against SARS-CoV-2. However, further in vitro and in vivo testing are required to confirm the findings of this study.
Leishmaniasis is a neglected tropical disease caused by the protozoan parasite Leishmania. It is ... more Leishmaniasis is a neglected tropical disease caused by the protozoan parasite Leishmania. It is endemic in more than 89 different countries worldwide. Sterol alpha‐14 demethylase (LdSDM), a sterol biosynthetic pathway enzyme in Leishmania donovani, plays an essential role in parasite survival and proliferation. Here, we used a drug repurposing approach to virtually screen the library of the Food and Drug Administration (FDA)‐approved drugs against LdSDM to identify the potential lead‐drug against leishmaniasis. Zafirlukast and avodart showed the best binding with LdSDM. Zafirlukast was tested for in vitro antileishmanial assay, but no significant effect on L. donovani promastigotes was observed even at higher concentrations. On the other hand, avodart profoundly inhibited parasite growth at relatively lower concentrations. Further, avodart showed a significant decrease in the number of intra‐macrophagic amastigotes. Avodart‐induced reactive oxygen species (ROS) in the parasites in a dose‐dependent manner. ROS induced by avodart led to the induction of apoptosis‐like cell death in the parasites as observed through annexin V/PI staining. Here, for the first time, we reported the antileishmanial activity and its possible mechanism of action of FDA‐approved drug, avodart, establishing a nice example of the drug‐repurposing approach. Our study suggested the possible use of avodart as an effective antileishmanial agent after further detailed validations.
Introduction: The ongoing coronavirus disease 2019 (COVID-19), which emerged in December 2019, is... more Introduction: The ongoing coronavirus disease 2019 (COVID-19), which emerged in December 2019, is a serious health concern throughout the world. Despite massive COVID-19 vaccination on a global scale, there is a rising need to develop more effective vaccines and drugs to curb the spread of coronavirus. Methodology: In this study, we screened the amino acid sequence of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 (the causative agent of COVID-19) for the identification of B and T cell epitopes using various immunoinformatic tools. These identified potent B and T cell epitopes with high antigenicity scores were linked together to design the multi-epitope vaccine construct. The physicochemical properties, overall quality, and stability of the designed vaccine construct were confirmed by suitable bioinformatic tools. Results: After proper in silico prediction and screening, we identified 3 B cell, 18 CTL, and 10 HTL epitopes from the RdRp protein sequence. The screened epitopes...
BackgroundRheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which mainly affe... more BackgroundRheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which mainly affects small joints, occurs most commonly in middle‐aged adults, and can be fatal in severe cases. The exact etiology of RA remains unknown. However, uncontrolled expression of pro‐inflammatory cytokines and chemokines can contribute to the pathogenesis of RA.AimIn the current study, we assessed the potential of serum concentrations of interleukin (IL)‐1β, IL‐6, tumor necrosis factor (TNF)‐α, IL‐8, and C‐C motif chemokine ligand (CCL)5 as early predictive markers for RA.MethodsIn addition to clinical examination, blood samples were collected from 100 Saudi patients recently diagnosed with early RA for basic and serological tests, including rheumatoid factor (RF), C‐reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Sera of 32 healthy individuals were used as controls. Specific enzyme‐linked immunosorbent assay was used to quantify the serum IL‐1β, IL‐6, TNF‐α, IL‐8, and CCL5 ...
Abbreviations DNA Deoxyribonucleic acid dNTP Deoxyribonucleotide triphosphate E. coli Escherichia... more Abbreviations DNA Deoxyribonucleic acid dNTP Deoxyribonucleotide triphosphate E. coli Escherichia coli FLA Free-living amoebae ITS Internal transcribed spacers KCl Magnesium chloride LB Luria-Bertini MgCl 2 Magnesium chloride NNA Non-nutrient agar PAM Primary amoebic meningoencephalitis PCR Polymerase chain reaction Abstract. Naegleria is well recognized for primary amoebic meningoencephalitis which always results into death. To date there is not a single report demonstrating molecular identification of Naegleria from water resources of Pakistan thus the aim of the proposed study. Here, in total 135 various water samples (like domestic tap water, municipal water, sea water, well water, tube well water, canal water, boring water, sewage water, lake water and stream water) were collected across Pakistan and evaluated for Naegleria species. Naegleria australiensis (pathogenic) and Naegleria lovaniensis (non pathogenic) were isolated on non nutrient agar plates and were further identifi...
Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found ... more Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found effective against an array of pathogens including fungi, bacteria, viruses, and protozoa. Here, we evaluated its antileishmanial activity and possible mechanism of action through different in vitro and in silico experiments. It inhibited the growth and proliferation of the parasites significantly with a IC50 value of 1.019 ± 0.116 mM in vitro. It also reduced the growth of intra-macrophagic amastigotes with a IC50 value of 0.2858 ± 0.01398 mM. It induced the reactive oxygen species (ROS) in parasites in a dose-dependent manner. Through 2,7-dichloro dihydro fluorescein diacetate (H2DCFDA) staining, it was observed that around 96.9% parasites were ROS positive at 2.0 mM concentration of hesperidin. The ROS generated led to the apoptosis of parasites in a dose-dependent manner as observed by annexin/PI staining. Molecular docking with one of the very important and unique drug-targets of Lei...
Shannon’s information theoretic perspective of communication helps one to understand the storage ... more Shannon’s information theoretic perspective of communication helps one to understand the storage and processing of information in one-dimensional sequences. An information theoretic analysis of 937 available completely sequenced prokaryotic genomes and 238 eukaryotic chromosomes is presented. Information content (Id) values were used to cluster these chromosomes. Chargaff’s second parity rule i.e compositional self-complementarity, an empirical fact is observed in all the genomes, except for the proteobacteria Candidatus Hodgkinia cicadicola. High information content, arising out of biased base composition in all the 14 chromosomes of Plasmodium falciparum is found among two other genomes of prokaryotes viz. Buchnera aphidicola str. Cc (Cinara cedri) and Candidatus Carsonella ruddii PV. Despite size and compositional variations, both prokaryotic and eukaryotic genomes do not deviate significantly from an equiprobable and random situation. Eukaryotic chromosomes of an organism tend t...
We report a 60-year-old Saudi patient with the clinical diagnosis of Alzheimer`s disease (AD) and... more We report a 60-year-old Saudi patient with the clinical diagnosis of Alzheimer`s disease (AD) and a novel mutation in the presenilin gene. We investigated mutations in the presenilin-1 gene in Saudi patients with AD using polymerase chain reaction and direct DNA sequencing methods. We extracted genomic DNA from the whole blood of both patients and normal control individuals. We sequenced and compared amplicons with the sequences of the respective exons of normal individuals as well as data available in GenBank. We detected a homozygous mutation (g-c) in exon 12, resulting in the missense mutation (Arg377Thr), in the DNA of a 60-year-old patient. We located this mutation in the cytoplasmic loop near the transmembrane domain 7.
Chalcones are secondary metabolites belonging to the flavonoid (C6-C3-C6 system) family that are ... more Chalcones are secondary metabolites belonging to the flavonoid (C6-C3-C6 system) family that are ubiquitous in edible and medicinal plants, and they are bioprecursors of plant flavonoids. Chalcones and their natural derivatives are important intermediates of the flavonoid biosynthetic pathway. Plants containing chalcones have been used in traditional medicines since antiquity. Chalcones are basically α,β-unsaturated ketones that exert great diversity in pharmacological activities such as antioxidant, anticancer, antimicrobial, antiviral, antitubercular, antiplasmodial, antileishmanial, immunosuppressive, anti-inflammatory, and so on. This review provides an insight into the chemistry, biosynthesis, and occurrence of chalcones from natural sources, particularly dietary and medicinal plants. Furthermore, the pharmacological, pharmacokinetics, and toxicological aspects of naturally occurring chalcone derivatives are also discussed herein. In view of having tremendous pharmacological po...
Leishmaniasis is a vector-borne disease caused by around 20 species of Leishmania. The main clini... more Leishmaniasis is a vector-borne disease caused by around 20 species of Leishmania. The main clinical forms of leishmaniasis are cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). VL is caused by Leishmania infantum in Central and South America, Mediterranean Basin, Middle East, and by L. donovani in Asia and Africa. Sterol C-24 methyltransferase (LdSMT) of L. donovani is a transferase enzyme of the sterol biosynthesis pathway. This pathway is one of the major targets for drug developments in Leishmania. Due to insufficient evidence about the exact function of SMT inside the cell and the uniqueness of the SMT enzyme in the Leishmania parasites made it a significant target for an effective drug development approach. We performed virtual screening of the Food and Drug Administration (FDA)-approved drug library against LdSMT and found simeprevir, an antiviral drug on top in the binding score. It showed a significant binding affinity with LdSMT. The binding was supported by hydrogen bonds and several other interactions. Simeprevir inhibited L. donovani growth of promastigotes with 50% inhibitory concentration (IC50 ) of 51.49 ± 5.87 μM. Further studies showed that simeprevir induced ROS generation in 44.7% of parasites at 125-μM concentration. Here, we for the first time reported simeprevir as an antileishmanial lead molecule using a drug repurposing approach.
Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activiti... more Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activities. Here, we evaluated its antileishmanial properties and its mechanism of action through different in silico and in vitro assays. Cynaroside exhibited antileishmanial activity in time- and dose-dependent manner with 50% of inhibitory concentration (IC50) value of 49.49 ± 3.515 µM in vitro. It inhibited the growth of parasite significantly at only 20 µM concentration when used in combination with miltefosine, a standard drug which has very high toxicity. It also inhibited the intra-macrophagic parasite significantly at low doses when used in combination with miltefosine. It showed less toxicity than the existing antileishmanial drug, miltefosine at similar doses. Propidium iodide staining showed that cynaroside inhibited the parasites in G0/G1 phase of cell cycle. 2,7-dichloro dihydro fluorescein diacetate (H2DCFDA) staining showed cynaroside induced antileishmanial activity through reac...
Leishmaniasis is a neglected tropical disease caused by trypanosomatid parasite belonging to the ... more Leishmaniasis is a neglected tropical disease caused by trypanosomatid parasite belonging to the genera Leishmania. Leishmaniasis is transmitted from one human to other through the bite of sandflies. It is endemic in around 98 countries including tropical and subtropical regions of Asia, Africa, Southern America, and the Mediterranean region. Sterol C‐24 methyltransferase (LdSMT) of Leishmania donovani (L. donovani) mediates the transfer of CH3‐group from S‐adenosyl methionine to C‐24 position of sterol side chain which makes the ergosterol different from cholesterol. Absence of ortholog in human made it potential druggable target. Here, we performed virtual screening of library of natural compounds against LdSMT to identify the potential inhibitor for it and to fight leishmaniasis. Gigantol, flavan‐3‐ol, and parthenolide showed the best binding affinity towards LdSMT. Further, based on absorption, distribution, metabolism, and excretion properties and biological activity prediction, gigantol showed the best lead‐likeness and drug‐likeness properties. Therefore, we further elucidated its antileishmanial properties. We found that gigantol inhibited the growth and proliferation of promastigotes as well as intra‐macrophagic amastigotes. Gigantol exerted its antileishmanial action through the induction of reactive oxygen species in dose‐dependent manner. Our study, suggested the possible use of gigantol as antileishmanial drug after further validations to overcome leishmaniasis.
The coronavirus disease 2019 (COVID-19), which emerged in December 2019, continues to be a seriou... more The coronavirus disease 2019 (COVID-19), which emerged in December 2019, continues to be a serious health concern worldwide. There is an urgent need to develop effective drugs and vaccines to control the spread of this disease. In the current study, the main phytochemical compounds of Nigella sativa were screened for their binding affinity for the active site of the RNA-dependent RNA polymerase (RdRp) enzyme of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The binding affinity was investigated using molecular docking methods, and the interaction of phytochemicals with the RdRp active site was analyzed and visualized using suitable software. Out of the nine phytochemicals of N. sativa screened in this study, a significant docking score was observed for four compounds, namely α-hederin, dithymoquinone, nigellicine, and nigellidine. Based on the findings of our study, we report that α-hederin, which was found to possess the lowest binding energy (–8.6 kcal/mol) and hence the best binding affinity, is the best inhibitor of RdRp of SARS-CoV-2, among all the compounds screened here. Our results prove that the top four potential phytochemical molecules of N. sativa, especially α-hederin, could be considered for ongoing drug development strategies against SARS-CoV-2. However, further in vitro and in vivo testing are required to confirm the findings of this study.
Leishmaniasis is a neglected tropical disease caused by the protozoan parasite Leishmania. It is ... more Leishmaniasis is a neglected tropical disease caused by the protozoan parasite Leishmania. It is endemic in more than 89 different countries worldwide. Sterol alpha‐14 demethylase (LdSDM), a sterol biosynthetic pathway enzyme in Leishmania donovani, plays an essential role in parasite survival and proliferation. Here, we used a drug repurposing approach to virtually screen the library of the Food and Drug Administration (FDA)‐approved drugs against LdSDM to identify the potential lead‐drug against leishmaniasis. Zafirlukast and avodart showed the best binding with LdSDM. Zafirlukast was tested for in vitro antileishmanial assay, but no significant effect on L. donovani promastigotes was observed even at higher concentrations. On the other hand, avodart profoundly inhibited parasite growth at relatively lower concentrations. Further, avodart showed a significant decrease in the number of intra‐macrophagic amastigotes. Avodart‐induced reactive oxygen species (ROS) in the parasites in a dose‐dependent manner. ROS induced by avodart led to the induction of apoptosis‐like cell death in the parasites as observed through annexin V/PI staining. Here, for the first time, we reported the antileishmanial activity and its possible mechanism of action of FDA‐approved drug, avodart, establishing a nice example of the drug‐repurposing approach. Our study suggested the possible use of avodart as an effective antileishmanial agent after further detailed validations.
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Papers by Abdul Dukhyil