STM Journals Peer-reviewed research from Consortium e-Learning Network

International Journal of Molecular Biotechnological Research Original Research

A Molecular Docking Study: Targetting HIV-1 Integrase Protein Against Selected Phytocompounds from Calophyllum Lanigerum

  1. Rishabh Kulkarni Departmentof Bioinformatics, BioNome, Bengaluru
  2. Shubham Wanarase Department of Bioinformatics, BioNome, Bengaluru

Abstract

Objectives: The most common form of HIV that causes AIDS is HIV-1. The World Health Organization has estimated roughly 75 million plus HIV-1 infections till date and roughly 40 million deaths (as of 2021). Thus, this study was done to identify natural compounds from Calophyllum lanigerum, a medicinal plant largely endemic to South-East Asia, to inhibit the spread of this disease. It did so by using molecular docking methods, Lipinski drug-likeness prediction, and the ADME analysis. Methods: The Protein Data Bank database was used to retrieve the HIV-1 Integrase protein (core domain with catalytic activity). The ligands were obtained from PubChem. PyRx was used for the docking analysis, and Biovia Discovery Studio Visualizer was used to display the receptor ligand interactions. Swiss-ADME, an online tool, was used to conduct the ADMET and Lipinski drug-likeliness study. Results: Five compounds from C. lanigerum have been identified by molecular docking studies as having potential binding affinity to prevent the integration of HIV-1 dsDNA (reverse transcribed) into the genome of human immunocytes, such as CD4+ T cells, which would have an impact on viral replication. According to the ADMET profile and drug likeness prediction, each of the top 5 compounds is safe and possesses drug-like qualities. Conclusion: The current investigation identifies 5 phytocompounds in total as having the strongest binding affinities and potential inhibitory effects on HIV-1 Integrase activity

Keywords

References (50)

  1. Greene WC 2007. A history of AIDS: Looking back to see ahead. Eur J Immunol 37 Suppl. 1: S94–S102 [PubMed] [Google Scholar]
  2. World Health Organization (WHO) [(accessed on 1 December 2017)];2017 Available online: http://www.who.int/hiv/data/epi_plhiv_2016_regions.png?ua=1
  3. Kharsany ABM, Karim QA. HIV Infection and AIDS in Sub-Saharan Africa: Current Status, Challenges and Opportunities. The Open AIDS Journal. 2016;10(1):34-48. doi:10.2174/1874613601610010034
  4. Powell MK, Benková K, Selinger P, Dogoši M, Kinkorová Luňáčková I, Koutníková H, et al. Opportunistic Infections in HIV-Infected Patients Differ Strongly in Frequencies and Spectra between Patients with Low CD4+ Cell Counts Examined Postmortem and Compensated Patients Examined Antemortem Irrespective of the HAART Era. PLOS ONE. 2016;11(9):e0162704. doi:10.1371/journal.pone.0162704
  5. UNAIDS; WHO (December 2007). "2007 AIDS epidemic update" (PDF). p. 16.
  6. Rodger AJ, Cambiano V, Bruun T, Vernazza P, Collins S, Degen O, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. The Lancet. 2019;393(10189):2428-2438. doi:10.1016/s0140-6736(19)30418-0
  7. Eisinger RW, Dieffenbach CW, Fauci AS. HIV Viral Load and Transmissibility of HIV Infection. JAMA. 2019;321(5):451. doi:10.1001/jama.2018.21167
  8. Cunningham AL, Donaghy H, Harman AN, Kim M, Turville SG. Manipulation of dendritic cell function by viruses. Current Opinion in Microbiology. 2010;13(4):524-529. doi:10.1016/j.mib.2010.06.002
  9. Garg H, Mohl J, Joshi A. HIV-1 Induced Bystander Apoptosis. Viruses. 2012;4(11):3020-3043. doi:10.3390/v4113020
  10. Doitsh G, Galloway NLK, Geng X, Yang Z, Monroe KM, Zepeda O, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature. 2013;505(7484):509-514. doi:10.1038/nature12940
  11. Kumar V (2012). Robbins Basic Pathology (9th ed.). p. 147. ISBN 978-1-4557-3787-1.
  12. Piot P, Abdool Karim SS, Hecht R, Legido-Quigley H, Buse K, Stover J, et al. Defeating AIDS—advancing global health. The Lancet. 2015;386(9989):171-218. doi:10.1016/s0140-6736(15)60658-4
  13. Günthard HF, Aberg JA, Eron JJ, Hoy JF, Telenti A, Benson CA, et al. Antiretroviral Treatment of Adult HIV Infection. JAMA. 2014;312(4):410. doi:10.1001/jama.2014.8722
  14. Anderson SJ, Cherutich P, Kilonzo N, Cremin I, Fecht D, Kimanga D, et al. Maximising the effect of combination HIV prevention through prioritisation of the people and places in greatest need: a modelling study. The Lancet. 2014;384(9939):249-256. doi:10.1016/s0140-6736(14)61053-9
  15. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 Infection with Early Antiretroviral Therapy. New England Journal of Medicine. 2011;365(6):493-505. doi:10.1056/nejmoa1105243
  16. Guay LA, Musoke P, Fleming T, Bagenda D, Allen M, Nakabiito C, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. The Lancet. 1999;354(9181):795-802. doi:10.1016/s0140-6736(99)80008-7
  17. Maartens G, Celum C, Lewin SR. HIV infection: epidemiology, pathogenesis, treatment, and prevention. The Lancet. 2014;384(9939):258-271. doi:10.1016/s0140-6736(14)60164-1
  18. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, Controlled Intervention Trial of Male Circumcision for Reduction of HIV Infection Risk: The ANRS 1265 Trial. PLoS Medicine. 2005;2(11):e298. doi:10.1371/journal.pmed.0020298
  19. Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. The Lancet. 2007;369(9562):643-656. doi:10.1016/s0140-6736(07)60312-2
  20. Sharifi-Rad J. Herbal antibiotics: Moving back into the mainstream as an alternative for “superbugs” Cell. Mol. Biol. 2016;62:1–2. [PubMed] [Google Scholar]
  21. WHO In vitro screening of traditional medicines for anti-HIV activity: Memorandum from a WHO meeting. Bull. World Health Organ. 1989;87:613–618. [PMC free article] [PubMed] [Google Scholar]
  22. WHO . Report of a Who Informal Consultation on Traditional Medicine and AIDS: In Vitro Screening for Anti-HIV Activity. WHO; Geneva, Switzerland: 1989. [Google Scholar]
  23. Kurapati KRV, Atluri VS, Samikkannu T, Garcia G, Nair MPN. Natural Products as Anti-HIV Agents and Role in HIV-Associated Neurocognitive Disorders (HAND): A Brief Overview. Frontiers in Microbiology. 2016;6. doi:10.3389/fmicb.2015.01444
  24. Li G, De Clercq E. HIV Genome-Wide Protein Associations: a Review of 30 Years of Research. Microbiology and Molecular Biology Reviews. 2016;80(3):679-731. doi:10.1128/mmbr.00065-15
  25. Singleton P, Sainsbury D, eds. (2006). "Hiv". Dictionary of microbiology & molecular biology (3rd ed.). Hoboken, NJ: Wiley. ISBN 9780470035450. OCLC 71223221.
  26. Varmus H, Brown PO. Retroviruses. In: Berg DE, Howe MM, editors. Mobile DNA. Washington, DC, USA: American Society of Microbiology; 1989. pp. 53–108. [Google Scholar]
  27. Ciuffi A. Mechanisms governing lentivirus integration site selection. Curr. Gene Ther. 2008;8(6):419–429. [PubMed] [Google Scholar]
  28. Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science. 2009;323(5919):1304–1307. [PubMed] [Google Scholar]
  29. Goff SP. Genetics of retroviral integration. Ann. Rev. Genet. 1992;26:527–544. [PubMed] [Google Scholar]
  30. Thang K Chiu 1, David R Davies (2004), Structure and Function of HIV-1 Integrase *
  31. Li, Xi-wen; Li, Jie; Stevens, Peter (n.d.). "Calophyllum (Linnaeus) Sp. Pl. 1: 513. 1753., 1841. 红厚壳属 hong hou ke shu". Flora of China. p. 1, 38.
  32. Kashman Y, Gustafson KR, Fuller RW, Cardellina JH, McMahon JB et al. The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum. J Med Chem. 1992;35(15):2735–2743. [PubMed] [Google Scholar] [Ref list]
  33. McKee TC, Fuller RW, Covington CD, Cardellina JH, Gulakowski RJ et al. New pyranocoumarins isolated from Calophyllum lanigerum and Calophyllum teysmannii. J Nat Prod. 1996;59(8):754–758. [PubMed] [Google Scholar] [Ref list]
  34. Dharmaratne HRW, Wijesinghe WNM. A trioxygenated diprenylated chromenxanthone from Calophyllum moonii. Phytochemistry. 1997;46(7):1293–1295. [Google Scholar] [Ref list]
  35. Kostova I., Raleva S., Genova P., Argirova R. Structure-activity relationships of synthetic coumarins as HIV-1 inhibitors. Bioinorg. Chem. Appl. 2006;2006:68274. [PMC free article] [PubMed] [Google Scholar]
  36. Kostova I. Coumarins as inhibitors of HIV reverse transcriptase. Curr. HIV. Res. 2006;4:347–363. [PubMed] [Google Scholar]
  37. Yu D., Suzuki M., Xie L., Morris-Natschke S.L., Lee K.H. Recent progress in the development of coumarin derivatives as potent anti-HIV agents. Med. Res. Rev. 2003;23:322–345. [PubMed] [Google Scholar]
  38. RCSB PDB (Research Collaboratory for Structural Bioinformatics – Protein Data Bank), Structure of Catalytic core domain of HIV-1 Integrase: (https://www.rcsb.org/structure/7D83)
  39. PubChem Database, Phytocompounds of C. lanigerum: (https://pubchem.ncbi.nlm.nih.gov
  40. /#query=[{%22query%22:%22Calophyllum%20lanigerum%22,%22tab%22:%22pubmed%22,%22collection%22:%22pubmed%22,%22id_type%22:%22pmid%22}]&collection=compound).
  41. Mcconkey BJ, Sobolev V, Edelman M. The performance of current methods in ligand-protein docking. Curr Sci 2002;83:845-55.
  42. Trott O, Olson AJ. Autodock vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31:455-61.
  43. O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open babel: An open chemical toolbox. J Cheminform 2011;3:33.
  44. Biovia DS. Discovery Studio Modeling Environment. San Diego: Dassault Systemes; 2015. Available from: https://www.scirp. org/(S(351jmbntv-nsjt1aadkposzje))/reference/
  45. referencespapers. aspx?referenceid=2450411 [Last accessed on 2022 Aug 05].
  46. Wikipedia Contributors. ADME. Wikipedia, The Free Encyclopedia; 2022. Available from: https://en.wikipedia.org/w/index. php?title=ADME&oldid=1087865915 [Last accessed on 2022 Aug 05].
  47. Swiss-ADME online server: http://www.swissadme.ch/
  48. ChemAGG online platform: https://admet.scbdd.com/ChemAGG/index/
  49. ProTox-II tool: (https://tox-new.charite.de/protox_II/)
  50. "HIV/AIDS Factsheet". World Health Organization. Retrieved 6 March 2022