Virtual screening of natural inhibitors to the predicted HBx protein structure of Hepatitis B Virus using molecular docking for identification of potential lead molecules for liver cancer

Pathak, Rajesh Kumar; Baunthiyal, Mamta; Taj, Gohar; Kumar, Anil

doi:10.6026/97320630010428

Cited by 26 publications

(11 citation statements)

References 24 publications

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“…Bilobetin is reported to inhibit the expression of the Epstein-Barr virus (EBV) genes (Lin et al, 1997). Different computational studies further revealed that bilobetin is a potent candidate for the treatment of herpes virus infection and hepatitis-B virus infection (Pathak et al, 2014;Ramaiah & Suresh, 2013). Another T. nucifera biflavonoid (ginkgetin) showed anti-herpesvirus activity against herpes simplex virus type 1 and type 2 (Adnan et al, 2020;Hayashi et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Computer aided identification of potential SARS CoV-2 main protease inhibitors from diterpenoids and biflavonoids of Torreya nucifera leaves

Ghosh

Chakraborty

Biswas

et al. 2020

Journal of Biomolecular Structure and Dynamics

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SARS CoV-2 is the causative agent of the pandemic disease COVID-19. There is an urgent need for effective drugs or vaccines which can effectively combat this outbreak. The main protease (Mpro), a key component for the SARS CoV-2 replication, is considered to be one of the important drug targets for developing anti-COVID-19 drugs. This SARS CoV-2 Mpro/cysteine protease has high sequence similarity with the same protease from SARS CoV-1. Previously, it has been shown experimentally that eight diterpenoids and four biflavonoids derived from the leaf of Torreya nucifera show inhibitory effect on the cleavage/catalytic activity of the SARS CoV-1 Mpro. But whether these phytochemicals exhibit any inhibitory effect on SARS CoV-2 Mpro is unclear. To understand this fact, here, we have adopted various in-silico approaches. Diterpenoids and biflavonoids those qualified pharmacological test (hinokiol, amentoflavone, bilobetin and ginkgetin) and two well-known Mpro inhibitors (N3 and lopinavir) were subjected for molecular docking studies. Only three biflavonoids (amentoflavone, bilobetin and ginkgetin) were selected by comparing their binding affinities with N3 and lopinavir. They interacted with two most important catalytic residues of Mpro (His41 and Cys145). Molecular dynamics studies further revealed that these three Mpro-biflavonoid complexes are highly stable and share a similar degree of compactness. Besides, these complexes experience less conformational fluctuations and more expansion than Mpro-N3 and/or Mpro-lopinavir complex. MM-GBSA and H-bond analysis further corroborated these findings. Altogether, our study suggested that these three biflavonoids could possibly inhibit the proteolytic/catalytic activity of SARS CoV-2 Mpro and might be useful for COVID-19 treatment.

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Section: Introductionmentioning

confidence: 99%

Computer aided identification of potential SARS CoV-2 main protease inhibitors from diterpenoids and biflavonoids of Torreya nucifera leaves

Ghosh

Chakraborty

Biswas

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…OSIRIS Property Explorer ( http: // www.organicchemistry. org/prog/peo/ ) was used to predict side effects, such as mutagenic, tumorigenic, irritant and reproductive effects which are also providing score for drug-relevant properties with respect to drug-likeness and overall drug-score [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Computer aided screening of natural compounds targeting the E6 protein of HPV using molecular docking

Mamgain

Sharma

Pathak³

et al. 2015

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The cancer profile in the Indian state of Uttarakhand reveals that the breast cancer is the most prevalent type of cancers in females followed by cervical and ovarian type. Literature survey shows that the E6 protein of Human Papilloma Virus-16 (HPV-16) is responsible for causing several forms of cancer in human. Therefore, it is of interest to screen HPV-16 E6 target protein with known natural compounds using computer aided molecular modeling and docking tools. The complete structure of E6 is unknown. Hence, the E6 structure model was constructed using different online servers followed by molecular docking of Colchine, Curcumin, Daphnoretin, Ellipticine and Epigallocatechin-3-gallate; five known natural compounds with best E6 protein model predicted by Phyre2 server. The screening exercise shows that Daphnoretin (with binding free energy of -8.3 kcal/mol), a natural compound derived from Wikstroemia indica has the top binding properties. Thus, it is of interest to consider the compound for further validation.

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“…The traditional Indian medicine curcumin (PubChem ID: CID_969516) structure published in literature was downloaded in SDF (standard data file) file from the database PubChem for computational study [ 26 ]. For molecular docking analysis, the SDF file of curcumin was converted into PDB (protein data bank) by using the software UCSF Chimera [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

Insights from the molecular docking of curcumin to the virulent factors of Helicobacter pylori

2015

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The domains of virulent (Ureα/β, VacA-p55, and CagA) factors of Helicobacter pylori play a pivotal role in developmental processes of numerous diseases including gastric cancer. The pharmacological role of curcumin indicates that it could regulate the signaling of virulent factors by interacting with active domains. However, the controlling mechanism of the curcumin interactions and the binding diversity on structural basis of virulent (Ureα/β, VacA-p55, and CagA) factors are unknown. Curcumin as therapeutic agent was filtered by using Lipinski rule׳s five and the druglikeness property for assessment of pharmacological properties. Here outcome of molecular docking presented the 3-D structure of curcumin complex, that interacted with especially conserved residues of target domains. The structure revealed that the curcumin complexation with domains of these proteins provided structural insight into the diverse nature of proteins (Ureα/β, VacA-p55, and CagA) recognition. In silico study elucidated that the broad specificity of curcumin was achieved by multiple binding mode mechanisms such as distinct hydrogen and hydrophobic interactions with involvement of binding energy. The higher score of curcumin in complexation with both subunits Ureα/β showed the stable binding, and less stability with VacA-p55 complexation with lower score. Curcumin exhibited good interaction with these targeted virulent factors, although extensive interactions of curcumin with Ureα/β subunits could have an important implication to prevent survival and colonisation of H. pylori in stomach.

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Virtual screening of natural inhibitors to the predicted HBx protein structure of Hepatitis B Virus using molecular docking for identification of potential lead molecules for liver cancer

Cited by 26 publications

References 24 publications

Computer aided identification of potential SARS CoV-2 main protease inhibitors from diterpenoids and biflavonoids of Torreya nucifera leaves

Computer aided identification of potential SARS CoV-2 main protease inhibitors from diterpenoids and biflavonoids of Torreya nucifera leaves

Computer aided screening of natural compounds targeting the E6 protein of HPV using molecular docking

Insights from the molecular docking of curcumin to the virulent factors of Helicobacter pylori

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