In-silico studies on Myo inositol-1-phosphate synthase of
            <i>Leishmania donovani</i>
            in search of anti-leishmaniasis

Sinha, Manoranjan; Jagadeesan, Rahul; Kumar, Neeraj; Saha, Satabdi; Kothandan, Gugan; Kumar, Diwakar

doi:10.1080/07391102.2020.1847194

Cited by 10 publications

(25 citation statements)

References 70 publications

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“…Absorption: Absorption is mainly calculated on account of water solubility, Caco2 permeability, human intestinal absorption, skin permeability, and whether the molecule is a P-glycoprotein substrate or inhibitor (Azam et al, 2014;Bhowmik et al, 2020;Sinha et al, 2020). The water solubility of the compound reflects at 25 °C.…”

Section: Pharmacokinetics Studiesmentioning

confidence: 99%

Discovering Potential RNA Dependent RNA Polymerase Inhibitors as Prospective Drugs Against COVID-19: An in silico Approach

et al. 2021

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COVID-19, caused by Severe Acute Respiratory Syndrome Corona Virus 2, is declared a Global Pandemic by WHO in early 2020. In the present situation, though more than 180 vaccine candidates with some already approved for emergency use, are currently in development against SARS-CoV-2, their safety and efficacy data is still in a very preliminary stage to recognize them as a new treatment, which demands an utmost emergency for the development of an alternative anti-COVID-19 drug sine qua non for a COVID-19 free world. Since RNA-dependent RNA polymerase (RdRp) is an essential protein involved in replicating the virus, it can be held as a potential drug target. We were keen to explore the plant-based product against RdRp and analyze its inhibitory potential to treat COVID-19. A unique collection of 248 plant compounds were selected based on their antiviral activity published in previous literature and were subjected to molecular docking analysis against the catalytic sub-unit of RdRp. The docking study was followed by a pharmacokinetics analysis and molecular dynamics simulation study of the selected best-docked compounds. Tellimagrandin I, SaikosaponinB2, Hesperidin and (-)-Epigallocatechin Gallate were the most prominent ones that showed strong binding affinity toward RdRp. All the compounds mentioned showed satisfactory pharmacokinetics properties and remained stabilized at their respective binding sites during the Molecular dynamics simulation. Additionally, we calculated the free-binding energy/the binding properties of RdRp-ligand complexes with the connection of MM/GBSA. Interestingly, we observe that SaikosaponinB2 gives the best binding affinity (∆Gbinding = −42.43 kcal/mol) in the MM/GBSA assay. Whereas, least activity is observed for Hesperidin (∆Gbinding = −22.72 kcal/mol). Overall our study unveiled the feasibility of the SaikosaponinB2 to serve as potential molecules for developing an effective therapy against COVID-19 by inhibiting one of its most crucial replication proteins, RdRp.

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Section: Pharmacokinetics Studiesmentioning

confidence: 99%

Discovering Potential RNA Dependent RNA Polymerase Inhibitors as Prospective Drugs Against COVID-19: An in silico Approach

et al. 2021

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“…The lethal concentration values (LC50) represent the concentration of a molecule necessary to cause 50% of fathead minnow death. For a given molecule, if the log LC50 < 0.5 mM (log LC50 < −0.3), then it is regarded as having high acute toxicity [29,30]. All three triazole compounds showed a satisfactory score that indicated that they are less toxic, except for Bisoctrizole (DB11262) (Table 4).…”

Section: Toxicitymentioning

confidence: 99%

“…The SARS-CoV-2 virus belongs to the β category of human coronaviruses [1][2][3], and its genomic organization is similar to that of other coronaviruses [4]. The viral genomic RNA (27)(28)(29)(30)(31)(32) codes both structural and non-structural proteins. The structural proteins include membrane (M), envelope (E), nucleocapsid (N), hemagglutinin-esterase (HE), and spike (S) proteins.…”

Section: Introductionmentioning

confidence: 99%

In Silico Identification and Validation of Organic Triazole Based Ligands as Potential Inhibitory Drug Compounds of SARS-CoV-2 Main Protease

2021

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The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, the search for anti-SARS-CoV-2 therapeutics through in silico analysis has become a highly promising field of research. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 main protease (Mpro). The SARS-CoV-2 main protease (Mpro) is known to play a prominent role in the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected from the DrugBank database). The results showed that four candidates (Bemcentinib, Bisoctrizole, PYIITM, and NIPFC) had high binding affinity values and had the potential to interrupt the main protease (Mpro) activities of the SARS-CoV-2 virus. The pharmacokinetic parameters of these candidates were assessed and through molecular dynamic (MD) simulation their stability, interaction, and conformation were analyzed. In summary, this study identified the most suitable compounds for targeting Mpro, and we recommend using these compounds as potential drug molecules against SARS-CoV-2 after follow up studies.

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“…The lethal concentration values (LC50) represent the concentration of a molecule necessary to cause 50% of fathead minnow death. For a given molecule, if the log LC50 < 0.5 mM (log LC50 < −0.3), then it is regarded as having high acute toxicity [26,27]]. All three triazole compounds showed a satisfactory score that indicated that they are less toxic, except for Bisoctrizole (DB11262) (Table 4).…”

Section: Toxicitymentioning

confidence: 99%

“…The SARS-CoV-2 virus belongs to the β category of human coronaviruses [1][2][3] and its genomic organization is like other coronaviruses [4]. The viral genomic RNA (27)(28)(29)(30)(31)(32) codes both structural and non-structural proteins. The structural proteins include: membrane (M), envelope (E), nucleocapsid (N), hemagglutinin-esterase (HE) and spike (S) proteins.…”

Section: Introductionmentioning

confidence: 99%

In silico identification and validation of organic triazole based ligands as potential inhibitory drug compounds of SARS-CoV-2 main protease

Sur

Sen

Komrsková

2021

Preprint

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The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, the search for anti-SARS-CoV-2 therapeutics through in silico analysis, has become a highly promising field of research. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 main protease (M pro ). The SARS-CoV-2 main protease (M pro ) is known to play a prominent role in the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected from the DrugBank database). The results showed that four candidates (Bemcentinib, Bisoctrizole, PYIITM and NIPFC) had high binding affinity values and had the potential to interrupt the main protease (M pro ) activities of the SARS-CoV-2 virus. The pharmacokinetic parameters of these candidates were assessed and they were then put through molecular dynamic (MD) simulation for stability, interaction and conformation analysis. In summary, we successfully identified the most suitable compounds for targeting SARS-CoV-2 main protease (M pro ). Based on our computational studies, we can suggest that the identified compounds can be used for further experimental approach as potential drug molecules against SARS-CoV-2.

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In-silico studies on Myo inositol-1-phosphate synthase of Leishmania donovani in search of anti-leishmaniasis

Cited by 10 publications

References 70 publications

Discovering Potential RNA Dependent RNA Polymerase Inhibitors as Prospective Drugs Against COVID-19: An in silico Approach

Discovering Potential RNA Dependent RNA Polymerase Inhibitors as Prospective Drugs Against COVID-19: An in silico Approach

In Silico Identification and Validation of Organic Triazole Based Ligands as Potential Inhibitory Drug Compounds of SARS-CoV-2 Main Protease

In silico identification and validation of organic triazole based ligands as potential inhibitory drug compounds of SARS-CoV-2 main protease

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