Aplidine, a Marine Natural Product Inhibits HIV-1 Entry and Its Replicating Enzymes by in silico Virtual Screening
AIDS is causing by infection of HIV, it is the deadliest and fear causing disease in the world and is rapidly expanding across the world. HIV infection has caused serious leads to many complications ultimately suppress the immune system of human. There are currently many antiviral synthetic agents are being practicing to treat or prevent HIV infection. Most of the available synthetic drugs are mainly used to inhibit the replication of the HIV. In the present work, we have carried out an in silico search of aplidine, a natural marine drug for anti-HIV viral agent. We have used 35 HIV-1 replicating enzymes and proteins against aplidine to know their molecular interactions to find out as potent drug. The aplidine have shown highest docking energy HIV-1 GP120 (-136.25) with followed by the crystal structure of the Prototype Foamy Virus (PFV) intasome in complex (-126.65), HIV-1 gp120 core complexed with CD4 and a neutralizing human antibody (-123.72), the structural studies of HIV-1 TAT protein (-121.69), HIV-RT (-118.4), crystal structure of HIV-1 JR-FL gp120 core protein (-117.47), structure of the native full-length HIV-1 capsid protein (-114.14), structure of HIV-1 capsid protein (-110.62). The less interactions was observed with immature retroviral capsid (-35.47), HIV-1 capsid protein (-52.18), ribonuclease H domain of HIV-1 reverse transcriptase (-87.56) and native full-length HIV-1 capsid protein (85.27) by aplidine. The aplidine have drug-like properties have exhibited remarkable docking profiles to all most all HIV-1 enzymes/ protein targets and it is relatively common herbal medicine, suggesting promise promising natural product and inexpensive HIV-1 therapy for this emerging global disease.
HIV-1, Aplidine, Molecular Docking, Natural Product
[1]
Cragg, G. M., Newman, D, J. (2004) Marine natural products and related compounds in clinical and advanced preclinical trials. J Nat Prod 67 (8): 1216–1238.
[2]
Zheng, L. H., Wang, Y. J., Sheng, J., Wang, F., Zheng, Y., Lin, X. K., Sun, M. (2011) Antitumour peptides from marine organisms. Mar Drugs 9 (10): 1840-1859.
[3]
Tom, G. (2002) Oceanography: an invitation to marine science 4th ed. United States: Brooks/Cole. 98.
[4]
Negi, B., Kumar, D., Rawat, D. S. (2016) Marine peptides as anticancer agents: a remedy to mankind by nature. Current Protein Pept Sci. University of Delhi - Department of Chemistry New Delhi, Delhi, India.
[5]
Broggini, M., Marchini, S. V., Galliera, E., Borsotti, P., Taraboletti, G., Erba, E., Sironi, M., Jimeno, J., Faircloth, G. T., Giavazzi, R., D’Incalci, M. (2003) Aplidine a new anticancer agent of marine origin, inhibits vascular endothelial growth factor (VEGF) secretion and blocks VEGF-VEGFR-1 (flt-1) autocrine loop in human leukemia cells MOLT-4. Leukemia 17 (1): 52-9.
[6]
Schwartmann, G., Da Rocha, A. B., Mattei, J., Lopes, R. (2003) Marine-derived anticancer agents in clinical trials. Expert Opin Investig Drugs. 12 (8): 1367-83.
[7]
Vera MD and Joullie MM. 2002. Natural products as probes of cell biology: 20 years of didemnin research. Med Res Rev 22 (2): 102-45.
[8]
Weiss, R. A. (1993) How does HIV cause AIDS?. Science 260 (5112): 1273–1279.
[9]
Jump, D. C., Garg, H., Mohl, J., Joshi, A. (2012) HIV-1 induced bystander apoptosis. Viruses 4 (11): 3020–43.
[10]
Cunningham, A. L., Donaghy, H., Harman, A. N., Kim, M., Turville, S. G. (2010) Manipulation of dendritic cell function by viruses. Cur Opinion Microb 13 (4): 524–529.
[11]
Kumaranayake, L., Watts, C. (2001) Resource allocation and priority setting of HIV/AIDS interventions: addressing the generalized epidemic in sub-Saharan Africa. J Inter Develop 13 (4): 451–466.
[12]
Centers for Disease Control and Prevention (CDCP). 2001. Revised guidelines for HIV counseling, testing, and referral. MMWR Recomm Rep. 50 (RR–19): 1–57.
[13]
Huang, Y., Yu, J., Lanzi, A., Yao, X., Andrews, C., Tsai, L., Gajjar, M., Sun, M., Seaman, M., Padte, N., Ho, D. (2016) Engineered bispecific antibodies with exquisite HIV-1 neutralizing activity. Cell 165 (7): 1621–1631.
[14]
Barblow, D. J., Buriani, A., Ehrman, T., Bosisio, E., Eberini, I., Hylands, P. J. (2012) In silico studies in Chinese herbal medicines research; evaluation of in silico methodologies and phytochemicals data source and a review of research to date. J Ethnoph 140 (3): 526-534.
[15]
Gu, W. G., Zhang, X., Yuan, J. F. (2014) Anti-HIV drugs development through computational methods. AAPS J 16 (4): 674-680.
[16]
Choi, S. B., Choong, Y. S., Saito, A., Wahab, H. A., Najimdin, N., Watanabe, N., Osada, H., Ong, E. B. B. (2014) In silico investigation of a HIV-1 vpr inhibitor binding site: potential for virtual screening and anti-HIV drug design. Mol Infor 33 (11-12); 742-748.
[17]
Jadaun, P., Khopkar, P., Kulkarni, S. (2016) Repurposing phytochemicals as anti-HIV agents. J Antivir Antiretrovir 8: 139-141.
[18]
Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N., Bourne, P. E. (2000) The protein data bank. Nucleic Acids Res 28: 235.
[19]
Seal., A., Aykkal, R., Ghosh, M. (2011) Docking study of HIV-1 reverse transcriptase with phytochemicals. Bioinfor 5 (10): 430-439.
[20]
Byler, K. G., Ogungbe, I. V., Setzer, W. N. (2016) In silico screening for anti-Zika virus phytochemicals. J Mol Grap Model 69: 78-91.
[21]
Hallenberger, S., Bosch, V., Angliker, H., Shaw, E., Klenk, H. D., Garten, W. (1992) Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature 360 (6402): 358–61.
[22]
Depenbrock, H., Peter, R., Faircloth, G. T., Manzanares, I., Jimeno, J., Hanauske, A. R. (1998) In vitro activity of aplidine, a new marine-derived anti-cancer compound, on freshly explanted clonogenic human tumour cells and haematopoietic precursor cells. Br J Cancer 78 (6): 739-44.
[23]
Celli, N., Gallardo, A. M., Rossi, C., Zucchetti, M., D'Incalci, M., Rotilio, D. (1999) Analysis of aplidine (dehydrodidemnin B), a new marine-derived depsipeptide, in rat biological fluids by liquid chromatography-tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 20; 731 (2): 335-343.
[24]
Nuijen, B., Bouma, M., Henrar, R. E., Floriano, P., Jimeno, J. M., Talsma, H., Kettenes-van den Bosch, J. J., Heck, A. J., Bult, A., Beijnen, J. H. (2000) Pharmaceutical development of a parenteral lyophilized formulation of the novel antitumor agent aplidine. PDA J Pharm Sci Technol 54 (3): 193-208.
[25]
Brandon, E. F., Sparidans, R. W., van Ooijen, R. D., Meijerman, I., Lazaro, L. L., Manzanares, I., Beijnen, J. H., Schellens, J. H. (2007) In vitro characterization of the human biotransformation pathways of aplidine, a novel marine anti-cancer drug. Invest New Drugs 25 (1): 9-19.
[26]
Faircloth, J. G., Rinehart, K., Nunez de Castro, I., Jimeno, J. (1996) Dehydrodidemnin B a new marine derived antitumour agent with activity against experimental tumour models. Ann Oncol 7: 34.
[27]
Pettersson, S., Perez-Neuno, V. I., Mena, M. P., Clotet, B., Este, J. A., Borrell, J. I., Teixido, J. (2010) Novel monocylam derivatives as HIV entry inhibitors: Design, synthesis, anti-HIV evaluation, and their interaction with the CXCR4 co-receptor. Chem Med Chem 5 (8): 1272-1281.
[28]
Sangeetha, B., Muthukumaran, R., Amutha, R. (2013) Pharmacophore modelling and electronic feature analysis of hydoxamic acid derivatives, the HIV integrase inhibitors. SAR and QSAR in Envir Res 24 (9): 753-771.
[29]
Bashir, T., Patgaonkar, M., Kumar, C. S., Pasi, A., Reddy, K. V. R. (2015) HbAHP-25, an In- silico designed peptide, inhibits HIV-1 entry by blocking gp120 binding to CD4 receptor. PLoS ONE 10 (4): e0124839.
[30]
Figueras, A., Miralles-Lluma, R., Flores, R., Rustullet, A., Busque, F., Figueredo, M., Font, J., Alibes, R., Marechal, J. D. (2012) Synthesis, anti-HIV activity studies and in silico reationalization of cyclobutane-fused nucleosides. Chem Med Chem 7 (6): 1044-1056.
[31]
Bensi, T., Mele, F., Derretti, M., Norelli, S., Daker, S. E. L., Chiocchette, A., Rojo, J. M. (2008) Evaluation of the antiretroviral effects of a PEG-conjugated peptide derived from human CD38. Expert Opinion Therapeutic Targets 13 (2): 141-152.
[32]
Williams, M. E., Tincho, M., Gabere, M., Uys, A., Meyer, M., Pretorius, A. (2016) Molecular validation of putative antimicrobial peptides for improved human immunodeficiency virus diagnostics via HIV protein p 24. J AIDS Clin Res 7: 571.
[33]
Freed, E. O. (2015) HIV-1 assembly, release and maturation. Nature Reviews Microb 13: 484-496.
[34]
Zhang, Z., Zhang, F., Yang, C., Qi, J., Gao, S., Li, S., Gu, Y., Xia, N. (2016) HIV-1 caspid as a target for antiviral therapy. J AIDS Clinical Therapy 7: 1.
[35]
Moonsamy, S., Bhakat, S., Soliman, M. E. S. (2014) Dynamic features of apo and bound HIV-nef protein reveals the anti-HIV dimerization inhibition mechanism. J Recep Signal Transd 35 (4): 346-356.
[36]
Narute, P. S., Smithgall, T. E. (2012) Nef alleles from all major HIV-1 clades activate Src-family kinases and enhance HIV-1 replication in an inhibitor-sensitive manner. PLoS ONE 7 (2): e32561.
[37]
Richman, D. D., Margolis, D. M., Delaney, M., Greene, W. C., Hazuda, D., Pomerantz, R. J. (2009) The challenge of finding a cure for HIV infection. Science 323 (5919): 1304-7.
[38]
Savarino, A. (2007) In silico docking of HIV-1 integrase inhibitors reveals a novel drug type acting on an enzyme/ DNA reaction intermediate. Retrovirology 4: 21.
[39]
Reddy, K. K., Singh, S. K., Tripathi, S. K., Selvaraj, C. (2013) Identification of potential HIV-1 ingrase strand transfer inhibitors: in silico virtual screening and QM/ MM docking studies. SAR and QSAR in Environ Res 24 (7): 581-595.
[40]
Liao, C., Nicklaus, M. C. (2012) Computer tools in the discovery of HIV-1 integrase inhibitors. Future Med Chem 2 (7): 1123-1140.
[41]
An de Waterbeemd, H., Gifford, E. (2003) ADMET in silico modeling; towards prediction paradise? Nature Reviews Drug Discovery 2: 192-204.
[42]
Raies, A. B., Bajic, V. B. (2016) In silico toxicology: computational for the prediction of chemical toxicity. Wiley interdiscip Rev Computer Mol Sci 6 (2): 147-172.
