Anti-HIV Drug Development Through Computational Methods

Gu, Wan-Gang; Zhang, Xuan; Yuan, Junfa

doi:10.1208/s12248-014-9604-9

Cited by 24 publications

(12 citation statements)

References 75 publications

(86 reference statements)

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“…About 40 million peoples are suffering from HIV infection and Africa region is a serious victim with 25 HIV-1 protease is another key enzyme which is essential for the HIV life-cycle [13]. The protease cleaves the newly translated chain and generates required protein components to assemble the infectious HIV virions [13,14]. HIV virions become uninfectious without operative HIV protease [15,16].…”

Section: Introductionmentioning

confidence: 99%

Docking Studies of HIV-1 Reverse Transcriptase and HIV-1 Integrase with Phytocompounds of Carissa Carandas L.

Singh

Nath

Sharma

2019

JCRHAP

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Background Carissa carandas L. is a well-known wild fruit plant distributed through-out the India and also present in other countries. The fruits are rich in nutrients and minerals. A number of medicinally important phytochemicals such as carrisone, carindone, carandinol, lupeol, scopoletin, stigmasterol, β-sitosterol, myo-inositol, β-amyrin, Des-n-methylnoracronycine etc. have been reported from the extract of this plant. Being safe and cost effective molecules, the activity of phytochemicals against HIV-1 enzymes needs to be screened. Objective The aim of this study was to screen the potent phytocompound of C. carandas against human immunodeficiency virus-1 using docking method. Methods Total nine compounds viz. carandinol, caridone, carrisone, lupeol, p-coumaric acid, gallic acid, rutin, scopoletin and ursolic acid were used for in-silico study towards drug development against human immunodeficiency virus-1 reverse transcriptase (HIV-1RT; PDB ID: 1REV) and human immunodeficiency virus-1 protease (PDB ID:1EBY) using Autodock software. Results The qualitative characterization of the extracts showed the presence of a number of phytochemicals such as phenolics, flavonoids, alkaloids, terepnoids, terpenes, steroids, glycosides etc. Carandinol was observed as most effective anti-HIV-1 molecule having lowest binding energy and small inhibition coefficient. Another compound, p-coumaric acid, showed least effectiveness against human immunodeficiency virus- 1 reverse transcriptase or human immunodeficiency virus-1 protease showing highest binding energy and inhibition coefficients among all the evaluated phytocompounds. Conclusion The in-silico study demonstrated that some phytoconstituents of C. carandas exhibit potential anti-human immunodeficiency virus -1 activity and hence can be optimized to develop as a drug candidate in future.

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Section: Introductionmentioning

confidence: 99%

Docking Studies of HIV-1 Reverse Transcriptase and HIV-1 Integrase with Phytocompounds of Carissa Carandas L.

Singh

Nath

Sharma

2019

JCRHAP

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“…For example, raltegravir (isentress), the first integrase inhibitor was approved by FDA in 2007 [ 13 ]. Presently about 30 antiretroviral drugs are prescribed for the clinical treatment of AIDS [ 14 ]. An improved knowledge of the structure and function viral proteins has led antiviral drug developers to design better antivirals to treat HIV infections [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

HIVprotI: an integrated web based platform for prediction and design of HIV proteins inhibitors

et al. 2018

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A number of anti-retroviral drugs are being used for treating Human Immunodeficiency Virus (HIV) infection. Due to emergence of drug resistant strains, there is a constant quest to discover more effective anti-HIV compounds. In this endeavor, computational tools have proven useful in accelerating drug discovery. Although methods were published to design a class of compounds against a specific HIV protein, but an integrated web server for the same is lacking. Therefore, we have developed support vector machine based regression models using experimentally validated data from ChEMBL repository. Quantitative structure activity relationship based features were selected for predicting inhibition activity of a compound against HIV proteins namely protease (PR), reverse transcriptase (RT) and integrase (IN). The models presented a maximum Pearson correlation coefficient of 0.78, 0.76, 0.74 and 0.76, 0.68, 0.72 during tenfold cross-validation on IC50 and percent inhibition datasets of PR, RT, IN respectively. These models performed equally well on the independent datasets. Chemical space mapping, applicability domain analyses and other statistical tests further support robustness of the predictive models. Currently, we have identified a number of chemical descriptors that are imperative in predicting the compound inhibition potential. HIVprotI platform (http://bioinfo.imtech.res.in/manojk/hivproti) would be useful in virtual screening of inhibitors as well as designing of new molecules against the important HIV proteins for therapeutics development.Electronic supplementary materialThe online version of this article (10.1186/s13321-018-0266-y) contains supplementary material, which is available to authorized users.

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“…The chemical structures and biological activity profiles of the inhibitors have been the subject of these reviews . In a review articles belonging to 2014, anti‐HIV‐1 agents have been discussed from the computer‐aided design point of view but, not all of the available HIV‐1 entry‐related targets were considered in that review article . The present review provides updated information regarding the latest reported small‐molecule HIV‐1 entrance inhibitors considering all the computational studies reported in the literature regarding HIV‐1 entry inhibitors since 2014.…”

Section: Introductionmentioning

confidence: 99%

HIV‐1 Entry Inhibitors: A Review of Experimental and Computational Studies

Rad

Saghaie

Fassihi

2018

Chemistry & Biodiversity

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The HIV-1 life cycle consists of different events, such as cell entry and fusion, virus replication, assembly and release of the newly formed virions. The more logical way to inhibit HIV transmission among individuals is to inhibit its entry into the immune host cells rather than targeting the intracellular viral enzymes. Both viral and host cell surface receptors and co-receptors are regarded as potential targets in anti-HIV-1 drug design process. Because of the importance of this topic it was decided to summarize recent reports on small-molecule HIV-1 entry inhibitors that have not been considered in the latest released reviews. All the computational studies reported in the literature regarding HIV-1 entry inhibitors since 2014 was also considered in this review.

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Anti-HIV Drug Development Through Computational Methods

Cited by 24 publications

References 75 publications

Docking Studies of HIV-1 Reverse Transcriptase and HIV-1 Integrase with Phytocompounds of Carissa Carandas L.

Docking Studies of HIV-1 Reverse Transcriptase and HIV-1 Integrase with Phytocompounds of Carissa Carandas L.

HIVprotI: an integrated web based platform for prediction and design of HIV proteins inhibitors

HIV‐1 Entry Inhibitors: A Review of Experimental and Computational Studies

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