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

Mamgain, Saril; Sharma, Pushpendra Kumar; Pathak, Rajesh Kumar; Baunthiyal, Mamta

doi:10.6026/97320630011236

Cited by 33 publications

(19 citation statements)

References 19 publications

(24 reference statements)

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“…Samant et al [ 42 ] studied the molecular interactions of human immunodeficiency virus antiviral drugs against HPV18 E6 through in silico approach. Mamgain et al [ 43 ] also observed the inhibitory effect of natural compounds such as colchine, curcumin, daphnoretin, ellipticine, epigallocatechin-3-gallate, etc. against HPV16 E6 protein using molecular docking [ 43 ].…”

Section: Resultsmentioning

confidence: 99%

In SilicoDocking to Explicate Interface between Plant-Originated Inhibitors and E6 Oncogenic Protein of Highly Threatening Human Papillomavirus 18

et al. 2015

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The leading cause of cancer mortality globally amongst the women is due to human papillomavirus (HPV) infection. There is need to explore anti-cancerous drugs against this life-threatening infection. Traditionally, different natural compounds such as withaferin A, artemisinin, ursolic acid, ferulic acid, (-)-epigallocatechin-3-gallate, berberin, resveratrol, jaceosidin, curcumin, gingerol, indol-3-carbinol, and silymarin have been used as hopeful source of cancer treatment. These natural inhibitors have been shown to block HPV infection by different researchers. In the present study, we explored these natural compounds against E6 oncoprotein of high risk HPV18, which is known to inactivate tumor suppressor p53 protein. E6, a high throughput protein model of HPV18, was predicted to anticipate the interaction mechanism of E6 oncoprotein with these natural inhibitors using structure-based drug designing approach. Docking analysis showed the interaction of these natural inhibitors with p53 binding site of E6 protein residues 108-117 (CQKPLNPAEK) and help reinstatement of normal p53 functioning. Further, docking analysis besides helping in silico validations of natural compounds also helped elucidating the molecular mechanism of inhibition of HPV oncoproteins.

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Section: Resultsmentioning

confidence: 99%

In SilicoDocking to Explicate Interface between Plant-Originated Inhibitors and E6 Oncogenic Protein of Highly Threatening Human Papillomavirus 18

et al. 2015

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“…Resveratrol (227), genestein (228)(229)(230), curcumin (223,231), ferulic acid (232) and quercitin (233) have shown synergistic anti-cancer properties and potentiation of apoptotic effects of ionizing radiation on cervical cancer cells primarily in vitro and in some studies in vivo (233). A ROSdependent mechanism has again been implicated in radiosensitivity mediated by at least some of the phytochemicals (223) With evolution of sophisticated molecular modeling, in silico approaches have been utilized to screen phytochemicals for their anti-HPV activity by specifically targeting molecular interaction of viral oncogenes with their respective cellular targets, thus rendering the viral oncogenes non-functional (234)(235)(236)(237). In silico docking of Carrageenan, Daphnoretin, Withaferin A and Artemisinin against HPV16 and HPV18 E6 revealed nearly 20X stronger inhibitory effect as compared to curcumin and tea polyphenol ECGC or jaceosidin found to functionally interfere with E6 (234)(235)(236).…”

Section: Amongmentioning

confidence: 99%

“…A ROSdependent mechanism has again been implicated in radiosensitivity mediated by at least some of the phytochemicals (223) With evolution of sophisticated molecular modeling, in silico approaches have been utilized to screen phytochemicals for their anti-HPV activity by specifically targeting molecular interaction of viral oncogenes with their respective cellular targets, thus rendering the viral oncogenes non-functional (234)(235)(236)(237). In silico docking of Carrageenan, Daphnoretin, Withaferin A and Artemisinin against HPV16 and HPV18 E6 revealed nearly 20X stronger inhibitory effect as compared to curcumin and tea polyphenol ECGC or jaceosidin found to functionally interfere with E6 (234)(235)(236). Further studies are needed to validate these findings in experimental settings.…”

Section: Amongmentioning

confidence: 99%

Therapeutic startegies for human papillomavirus infection and associated cancers

et al. 2018

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Human papillomavirus (HPV) infection is linked to development of cancer of cervix, vagina, vulva, penis, ano-genital and non-genital oro-pharyngeal sites. HPV being a sexually transmitted virus infects both genders equally but with higher chances of pathological outcome in women. In the absence of organized screening programs, women report HPV-infected lesions at relatively advanced stages where they are subjected to standard treatments that are not HPV-specific. HPV infection-driven lesions usually take 10-20 years for malignant progression and are preceded by well-characterized pre-cancer stages. Despite availability of window for pharmacological intervention, therapeutic that could eradicate HPV from infected lesions is currently lacking. A variety of experimental approaches have been made to address this lacuna and there has been significant progress in a number of lead molecules which are in different stages of clinical and pre-clinical development. Present review provides a brief overview of the magnitude of the problem and current status of research on promising lead molecules, formulations and therapeutic strategies that showed potential to translate to clinically-viable HPV therapeutics to counteract this reproductive health challenge.

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“…This was performed using the Discovery Studio 4.1 Visualizer (http://accelrys.com/products/discovery-studio) [28]. Docked structures showing amino acid residues involved in the docking as well as the interactions between respective residues and ligand were image captured using image save option in Discovery Studio 4.1 Visualizer.…”

Section: Interfering Amino Acids and Their Interactions Involvedmentioning

confidence: 99%

INHIBITION OF Α-Amylase AND Α-Glucosidase BY (6rs)-22-Hydroxy-23,24,25,26,27-Pentanor-Vitamin-D3-6,19-Sulfur DIOXIDE-ADDUCT, MANOALIDE AND 5β-Cholestane-3α,7α,12α,24,25,26-Hexol ISOLATED FROM ACETONE EXTRACT OF HELIANTHUS ANNUUS L. SEEDS

Sonkamble

Wagh

Kamble

2018

Int J Pharm Pharm Sci

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Objective: This investigation includes characterization of phytochemicals from acetone extract of Helianthus annuus L. seeds responsible for α-amylase and α-glucosidase inhibition revealed from in vitro and in silico approaches. Methods:Seed extract was qualitatively and quantitatively analysed for the presence of bioactive molecules. In vitro α-amylase and α-glucosidase inhibition assays and kinetics studies for α-glucosidase were done. Thin layer chromatography (TLC) autography of extract was done to screen potent inhibitors and characterized by high-resolution liquid chromatography-mass spectrometry (HR LC-MS). Characterized molecules were further used for in silico studies.Results: Qualitative investigation reveals the presence of flavonoids, glycosides, alkaloids, terpenoids, and steroids. Quantitative analysis for total phenolic content and total flavonoid content of the extract was 0.1±0.005 mg/ml GAE and 0.025±0.003 mg/ml QE respectively. Percent inhibition of α-amylase and α-glucosidase ascertained in presence of extract was 60.42±0.6 and 83.22±0.18 at 0.01 mg while 36.24±0.81 and 37.67±0.15 at 0.005 mg of extracts for both enzymes respectively. Kinetics studies of α-glucosidase inhibition illustrated the non-competitive type of inhibition. TLC autography inhibition patterns were characterized by HR LC-MS. Characterized molecules on docking revealed (6RS)- 22-hydroxy-23,24,25,26,27-pentanor-vitamin-D3-6,19-sulfurdioxide-adduct, manoalide and 5β-cholestane-3α,7α,12α,24,25,26-hexol as the best docked molecules with lowest binding energies of-12.5,-11 and-10.2 kcal/mol for α-amylase and-14.2,-11 and-11.2 kcal/mol for α-glucosidase respectively. Conclusion:Results clearly suggested that (6RS)-22-hydroxy-23,24,25,26,27-pentanor-vitamin-D3-6,19-sulfurdioxide-adduct, manoalide and 5β-cholestane-3α,7α,12α,24,25,26-hexol could be considered as lead molecules for the discovery of potent antidiabetic agents.

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

Cited by 33 publications

References 19 publications

In SilicoDocking to Explicate Interface between Plant-Originated Inhibitors and E6 Oncogenic Protein of Highly Threatening Human Papillomavirus 18

In SilicoDocking to Explicate Interface between Plant-Originated Inhibitors and E6 Oncogenic Protein of Highly Threatening Human Papillomavirus 18

Therapeutic startegies for human papillomavirus infection and associated cancers

INHIBITION OF Α-Amylase AND Α-Glucosidase BY (6rs)-22-Hydroxy-23,24,25,26,27-Pentanor-Vitamin-D3-6,19-Sulfur DIOXIDE-ADDUCT, MANOALIDE AND 5β-Cholestane-3α,7α,12α,24,25,26-Hexol ISOLATED FROM ACETONE EXTRACT OF HELIANTHUS ANNUUS L. SEEDS

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