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

Abstract

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.

Molecular Docking, Validation, Dynamics Simulations, and Pharmacokinetic Prediction of Phytochemicals Isolated From Croton dichogamus Against the HIV-1 Reverse Transcriptase

“…Furthermore, it displayed hydrophobic interactions with residues in the active binding site including – ASN 265, GLN 269, GLU 378, GLY 352, HIS 96, ILE 94, LYS 350, LYS 353, LYS 374, PRO 95, SER 268, TYR 232, TYR 339. Similar interacting amino acids were reported previously by Singh et al, 51 Seal et al 52 …”

“…Furthermore, it displayed hydrophobic interactions with residues in the active binding site including -ASN 265, GLN 269, GLU 378, GLY 352, HIS 96, ILE 94, LYS 350, LYS 353, LYS 374, PRO 95, SER 268, TYR 232, TYR 339. Similar interacting amino acids were reported previously by Singh et al, 51 Seal et al 52 Aleuritolic acid forms two hydrogen bonds with LYS353 with an interatomic distance of 2.77 Å and 3.62 Å. The hydroxyl group at position 1 and the carboxyl acid moiety at the 11th position have a role in forming these hydrogen bonds.…”