Identification of new DNA gyrase inhibitors based on bioactive compounds from streptomyces: structure-based virtual screening and molecular dynamics simulations approaches

Kalhor, Hourieh; Sadeghi, Sedigheh; Marashiyan, Mahya; Kalhor, Reyhaneh; Gharehbolagh, Sanaz Aghaei; Eidgahi, Mohammad Reza Akbari; Rahimi, Hamzeh

doi:10.1080/07391102.2019.1588784

Cited by 19 publications

(12 citation statements)

References 60 publications

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“…Virtual screening approaches are extensively being applied in designing and development of new drugs. In this regard, one of the most common virtual screening techniques is structure-based virtual screening (SBVS) which only needs the three-dimensional structure of the interested protein and identifying its potential binding pockets to choose drugs, which interact strongly with these binding pockets, from large databases Kalhor, Sadeghi, et al, 2020;Shiri et al, 2018Shiri et al, , 2019.…”

Section: Methodsmentioning

confidence: 99%

Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches

Kalhor

Sadeghi

Abolhasani

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Most recently, the new coronavirus (SARS-CoV-2) has been recognized as a pandemic by the World Health Organization (WHO) while this virus shares substantial similarity with SARS-CoV. So far, no definitive vaccine or drug has been developed to cure Covid-19 disease, since many important aspects about Covid-19 such as pathogenesis and proliferation pathways are still unclear. It was proven that human ACE2 is the main receptor for the entry of Covid-19 into lower respiratory tract epithelial cells through interaction with SARS-CoV-2 S protein. Based on this observation, it is expected that the virus infection can be inhibited if protein-protein interaction is prevented. In this study, using structurebased virtual screening of FDA databases, several lead drugs were discovered based on the ACE2binding pocket of SARS-CoV-2 S protein. Then, binding affinity, binding modes, critical interactions, and pharmaceutical properties of the lead drugs were evaluated. Among the previously approved drugs, Diammonium Glycyrrhizinate, Digitoxin, Ivermectin, Rapamycin, Rifaximin, and Amphotericin B represented the most desirable features, and can be possible candidates for Covid-19 therapies. Furthermore, molecular dynamics (MD) simulation was accomplished for three S protein/drug complexes with the highest binding affinity and best conformation and binding free energies were also computed with the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method. Results demonstrated the stable binding of these compounds to the S protein; however, in order to confirm the curative effect of these drugs, clinical trials must be done.

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Section: Methodsmentioning

confidence: 99%

Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches

Kalhor

Sadeghi

Abolhasani

et al. 2020

Journal of Biomolecular Structure and Dynamics

Self Cite

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show abstract

“…The RMSF of C-alpha atoms of protein were higher in between residues 175 to 275 of TYR, which is binding region for Kojic acid and its derivative, rest of the structure remained stable (Fig 8B). protein structure compactness and stability can correctly be de ned in terms of the radius of gyration (Rg) (Bhardwaj et al, 2020;Kalhor et al, 2020). The average Rg value for apo-protein is depicted near 2.13 nm by a small fall from the initial to the end of MD simulation.…”

Section: Drug-likeness and In Silico Adme Prediction Analysismentioning

confidence: 99%

In silico ADMET, molecular docking and molecular simulation-based study of glabridin’s natural and semisynthetic derivatives as potential tyrosinase inhibitors

Kumari

Kumar

Sulabh

et al. 2022

Preprint

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Objective Hyper-pigmentation conditions may develop due to erroneous melanogenesis cascade which leads to excess melanin production. Recently, inhibition of tyrosinase is the main focus of investigation as it majorly contributes to melanin production. This inhibition property can be exploited in medicine, agriculture, and in cosmetics. Present study aims to find a natural and safe alternative molecule as tyrosinase inhibitor. Methods In this study, human tyrosinase enzyme was modelled due to unavailability of its crystal structure to look into the degree of efficacy of glabridin and its 15 derivatives as tyrosinase inhibitor. Docking was performed by Autodock Vina at the catalytic core enzyme. Glabridin effects on melanoma cell lines was also elucidated by analysing cytotoxicity and effect on melanin production. Computational ADME analysis was done by SwissADME. Molecular dynamic simulation was also performed to further evaluate the interaction profile of these molecules and kojic acid (positive inhibitor) with respect to apo protein. Results Notably, four derivatives 5’-formylglabridin, glabridin dimer, 5’-prenyl glabridin and R-glabridin exhibited better binding affinity than glabridin. Glabridin effectively inhibited melanin production in a dose dependent manner. Among these, 5’-formylglabridin displayed highest binding affinity with docking score – 9.2 kcal/mol. Molecular properties and bioactivity analysis by Molinspiration web server and by SwissADME also presented these molecules as potential drug candidates. Conclusion The study explores the understanding for the development of suitable tyrosinase inhibitor/s for the prevention of hyperpigmentation. However, a detailed in vivo study is required for glabridin derivatives to suggest these molecules as anti-melanogenic compound.

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“…In Eq. 4, c represents a coefficient of surface tension, and b represents a fitting parameter (Hourieh et al, 2019). All energy components in Eq.…”

Section: Binding Free Energymentioning

confidence: 99%

“…Indicating that the residues of Nsp15-Olaparib complex have the lowest fluctuations. The radius of gyration (Rg) is defined as an indication of the structure compactness and stability of a protein Hourieh et al, 2019). Therefore, values of Rg for all complexes were calculated during MD simulations.…”

Section: Molecular Dynamics Simulation Analysismentioning

confidence: 99%

Prediction of potential inhibitors against SARS-CoV-2 endoribonuclease: RNA immunity sensing

Al-Rashedi

Munahi

AlObaidi

2020

Journal of Biomolecular Structure and Dynamics

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Identification of new DNA gyrase inhibitors based on bioactive compounds from streptomyces: structure-based virtual screening and molecular dynamics simulations approaches

Cited by 19 publications

References 60 publications

Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches

Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches

In silico ADMET, molecular docking and molecular simulation-based study of glabridin’s natural and semisynthetic derivatives as potential tyrosinase inhibitors

Prediction of potential inhibitors against SARS-CoV-2 endoribonuclease: RNA immunity sensing

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