Computer-Aided Design of Novel HIV-1 Entry Inhibitors Based on Glycosphingolipids

A. M. Andrianov ; Yu. V. Kornoushenko ; I. A. Kashyn ; A. V. Tuzikov

Matematičeskaâ biologiâ i bioinformatika, Tome 8 (2013) no. 1, pp. 258-275.

Résumé

Twelve water-soluble analogs of glycosphingolipid $\beta$-galactosylceramide, which present potential anti-HIV agents able to specifically and effectively interact with the conserved structural motifs of the HIV-1 V3 loop containing the envelope gp120 residues critical for cell tropism, were designed by computer modeling. The compounds obtained were shown to exhibit the promising basic structures for the development of novel, potent and broad antiviral drugs.

Bibliographie

[1] Hartley O., Klasse P. J., Sattentau Q. J., Moore J. P., “V3: HIV's Switch-Hitter”, AIDS Res. Hum. Retroviruses, 21 (2005), 171–189 | DOI

[2] Sirois S., Sing T., Chou K. C., “HIV-1 gp120 V3 loop for structure-based drug design”, Curr. Protein Pept. Sci., 6 (2005), 413–422 | DOI

[3] Andrianov A. M., “Human immunodeficiency virus-1 gp120 V3 loop for anti-acquired immune deficiency syndrome drug discovery: computer-aided approaches to the problem solving”, Expert Opin. Drug. Discov., 6 (2011), 419–435 | DOI

[4] LaRosa G. J., Davide J. P., Weinhold K., Waterbury J. A., Profy A. T., Lewis J. A., Langlois A. J., Dressman G. R., Boswell R. N., Shadduk P., Holley L. H., Karplus M., Bolognesi D. P., Matthews T. J., Emini E. A., Putney S. D., “Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant”, Science, 249 (1990), 932–935 | DOI

[5] Tian H., Lan C., Chen Y. H., “Sequence variation and consensus sequence of V3 loop on HIV-1 gp120”, Immunol. Lett., 83 (2002), 231–233 | DOI

[6] Andrianov A. M., Anishchenko I. V., Tuzikov A. V., “Discovery of novel promising targets for anti-AIDS drug developments by computer modeling: application to the HIV-1 gp120 V3 loop”, J. Chem. Inf. Model., 51 (2011), 2760–2767 | DOI

[7] Andrianov A. M., Kornoushenko Yu. V., Anishchenko I. V., Eremin V. F., Tuzikov A. V., “Structural analysis of the envelope gp120 V3 loop for some HIV-1 variants circulating in the countries of Eastern Europe”, J. Biomol. Struct. Dynam., 2012, 1–19 | DOI

[8] Jiang X., Burke V., Totrov M., Williams C., Cardozo T., Gorny M. K., Zolla-Pazner S., Kong X. P., “Conserved structural elements in the V3 crown of HIV-1 gp120”, Nat. Struct. Mol. Biol., 17 (2010), 955–961 | DOI

[9] Bhat S., Spitalnik S. L., Gonzalez-Scarano F., Silberberg D. H., “Galactosylceramide or a derivative is an essential component of the neural receptor for human immunodeficiency virus type 1 envelope glycoprotein gp120”, Proc. Natl. Acad. Sci. USA, 88 (1991), 7131–7134 | DOI

[10] Fantini J., Cook D. G., Nathanson N., Spitalnik S. L., Gonzalez-Scarano F., “Infection of colonic epithelial cell lines by type 1 human immunodeficiency virus is associated with cell surface expression of galactosylceramide, a potential alternative gp120 receptor”, Proc. Natl. Acad. Sci. USA, 90 (1993), 2700–2704 | DOI

[11] Fantini J., Hammache D., Delézay O., Yahi N., André-Barrès C., Rico-Lattes I., Lattes A., “Synthetic soluble analogs of galactosylceramide (GalCer) bind to the V3 domain of HIV-1 gp120 and inhibit HIV-1-induced fusion and entry”, J. Biol. Chem., 272 (1997), 7245–7252 | DOI

[12] Yahi N., Sabatier J. M., Nickel P., Mabrouk K., Gonzalez-Scarano F., Fantini J., “Suramin inhibits binding of the V3 region of HIV-1 envelope glycoprotein gp120 to galactosylceramide, the receptor for HIV-1 gp120 on human colon epithelial cells”, J. Biol. Chem., 269 (1994), 24349–24353

[13] Cook D. G., Fantini J., Spitalnik S. L., Gonzalez-Scarano F., “Binding of human immunodeficiency virus type I (HIV-1) gp120 to galactosylceramide (GalCer): relationship to the V3 loop”, Virology, 201 (1994), 206–214 | DOI

[14] Garg H., Francella N., Tony K. A., Augustine L. A., Barchi J. J. Jr., Fantini J., Puri A., Mootoo D. R., Blumenthal R., “Glycoside analogs of beta-galactosylceramide, a novel class of small molecule antiviral agents that inhibit HIV-1 entry”, Antiviral Res., 80 (2008), 54–61 | DOI

[15] LaBell R. Y., Jacobsen N. E., Gervay-Hague J., O'Brien D. F., “Synthesis of novel glycolipids that bind HIV-1 Gp120”, Bioconjug. Chem., 13 (2002), 143–149 | DOI

[16] Augustin L. A., Fantini J., Mootoo D. R., “C-Glycoside analogues of beta-galactosylceramide with a simple ceramide substitute: synthesis and binding to HIV-1 gp120”, Bioorg. Med. Chem., 14 (2006), 1182–1188 | DOI

[17] Berman H. M., Westbrook J., Feng Z., Gilliland G., Bhat T. N., Weissig H., Shindyalov I. N., Bourne P. E., “The Protein Data Bank”, Nucl. Acids Res., 28 (2000), 235–242 | DOI

[18] Andrianov A. M., Anishchenko I. V., Kisel M. A., Kornoushenko Yu. V., Nikolayevich V. A., Eremin V. F., Kucherov I. I., Tuzikov A. V., “Computer-Aided Design of Novel HIV-1 Entry Inhibitors Targeting the Envelope gp120 V3 Loop”, Biopolym. Cell, 28 (2012), 468–476 | DOI

[19] Curtiss L. A., Raghavachari K., Redfern P. C., Pople J. A., “Assessment of Gaussian-3 and density functional theories for a larger experimental test set”, J. Chem. Phys., 112 (2000), 7374–7383 | DOI

[20] Curtiss L. A., Raghavachari K., “Gaussian-3 and related methods for accurate thermochemistry”, Theor. Chem. Acc., 108 (2002), 61–70 | DOI

[21] Wang J., Wolf R. M., Caldwell J. W., Kollman P. A., Case D. A., “Development and testing of a general Amber force field”, J. Comput. Chem., 25 (2004), 1157–1174 | DOI

[22] Ben-Israel A., “A modified Newton–Rafson method for the solution of systems of equations”, Israel J. Math., 3 (1965), 94–98 | DOI | MR | Zbl

[23] Bayly C. I., Cieplak P., Cornell W., Kollman P. A., “Well-behaved electrostatic potential based method using charge restraints for determining atom-centered charges: the RESP model”, J. Phys. Chem., 97 (1993), 10269–10280 | DOI

[24] Cornell W. D., Cieplak P., Bayly C. I., Kollmann P. A., “Application of the RESP charges to calculate conformational energies, hydrogen bond energies, and free energies of solvation”, J. Am. Chem. Soc., 115 (1993), 9620–9631 | DOI

[25] Andrianov A. M., Kornoushenko Yu. V., Anishchenko I. V., Eremin V. F., Tuzikov A. V., “Structural analysis of the envelope gp120 V3 loop for some HIV-1 variants circulating in the countries of Eastern Europe”, J. Biomol. Struct. Dynam., 2012, 1–19

[26] Huang C. C., Tang M., Zhang M. Y., Majeed S., Montabana E., Stanfield R. L., Dimitrov D. S., Korber B., Sodroski J., Wilson I. A., Wyatt R., Kwong P. D., “Structure of a V3-containing HIV-1 gp120 core”, Science, 310 (2005), 1025–1028 | DOI

[27] Trott O., Olson A. J., “AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading”, J. Comput. Chem., 31 (2010), 455–461

[28] Kirkpatrick K. S., Gelatt C. D., Vecchi M. P., “Optimization by simulated annealing”, Science, 220 (1983), 671–680 | DOI | MR | Zbl

[29] Case D. A., Darden T. A., Cheatham T. E., Simmerling C. L., Wang J., Duke R. E., Luo R., Crowley M., Walker R. C., Zhang W., Merz K. M., Wang B., Hayik S., Roitberg A., Seabra G., Kolossvary I., Wong K. F., Paesani F., Vanicek J., Wu X., Brozell S. R., Steinbrecher T., Gohlke H., Yang L., Tan C., Mongan J., Hornak V., Cui G., Mathews D. H., Seetin M. G., Sagui C., Babin V., Kollman P. A., AMBER 11, University of California, San Francisco, 2010 | Zbl

[30] Jorgensen W. L., Chandrasekhar J., Madura J. D., Impey R. W., Klein M. L., “Comparison of simple potential functions for simulating liquid water”, J. Chem. Phys., 79 (1983), 926–935 | DOI

[31] Massova I., Kollman P. A., “Computational alanine scanning to probe protein-protein interactions: a novel approach to evaluate binding free energies”, J. Am. Chem. Soc., 121 (1999), 8133–8143 | DOI

[32] Ablameiko S. V., Abramov S. M., Anischenko V. V., Medvedev S. V., Paramonov N. N., Chizh O. P., Superkompyuternye konfiguratsii SKIF, Ob'edinennyi institut problem informatiki NAN Belarusi, Minsk, 2005

[33] Durranta J. D., McCammon J. A., “BINANA: A novel algorithm for ligand-binding characterization”, J. Mol. Graph. Model., 29 (2011), 888–893 | DOI

[34] Anischenko I. V., Kashin I. A., Tuzikov A. V., Andrianov A. M., “Analiz energii spetsificheskikh vzaimodeistvii glikolipidov — potentsialnykh anti-VICh agentov — s petlei V3 belka gp120 obolochki virusa”, Doklady NAN Belarusi, 56:4 (2012), 63–69

[35] Fantini J., Yahi N., “Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: common mechanisms in neurodegenerative diseases”, Expert Rev. Mol. Med., 12:e27 (2010), 1–22

[36] Mahfoud R., Garmy N., Maresca M., Yahi N., Puigserver A., Fantini J., “Identification of a common sphingolipid-binding domain in Alzheimer, prion, and HIV-1 proteins”, J. Biol. Chem., 277 (2002), 11292–11296 | DOI

[37] Yahi N., Aulas A., Fantini J., “How Cholesterol Constrains Glycolipid Conformation for Optimal Recognition of Alzheimer's $\beta$ Amyloid Peptide (Abeta1-40)”, PLoS One, 5:2 (2010), e9079 | DOI

[38] de Parseval A., Bobardt M. D., Chatterji A., Chatterji U., Elder J. H., David G., Zolla-Pazner S., Farzan M., Lee T. H., Gallay P. A., “A highly conserved arginine in gp120 governs HIV-1 binding to both syndecans and CCR5 via sulfated motifs”, J. Biol. Chem., 280 (2005), 39493–39504 | DOI

[39] Wang W. K., Dudek T., Zhao Y. J., Brumblay H. G., Essex M., Lee T. H., “CCR5 coreceptor utilization involves a highly conserved arginine residue of HIV type 1 gp120”, Proc. Natl. Acad. Sci. USA, 95 (1998), 5740–5745 | DOI

[40] Ogert R. A., Lee M. K., Ross W., Buckler-White A., Martin M. A., Cho M. W., “N-linked glycosylation sites adjacent to and within the V1/V2 and the V3 loops of dualtropic human immunodeficiency virus type 1 isolate DH12 gp120 affect coreceptor usage andcellular tropism”, J. Virol., 75 (2001), 5998–6006 | DOI

[41] McCaffrey R. A., Saunders C., Hensel M., Stamatatos L., “N-linked glycosylation of the V3 loop and the immunologically silent face of gp120 protects human immunodeficiency virus type 1 SF162 from neutralization by anti-gp120 and anti-gp41 antibodies”, J. Virol., 78 (2004), 3279–3295 | DOI

[42] Teeraputon S., Louisirirojchanakul S., Auewarakul P., “N-linked glycosylation in C2 region of HIV-1 envelope reduces sensitivity to neutralizing antibodies”, Viral Immunol., 18 (2005), 343–353 | DOI

[43] Li Y., Rey-Cuille M. A., Hu S. L., “N-linked glycosylation in the V3 region of HIV type 1 surface antigen modulates coreceptor usage in viral infection”, AIDS Res. Hum. Retroviruses, 17 (2001), 1473–1479 | DOI

[44] Malenbaum S. E., Yang D., Cavacini L., Posner M., Robinson J., Cheng-Mayer C., “The N-terminal V3 loop glycan modulates the interaction of clade A and B human immunodeficiency virus type 1 envelopes with CD4 and chemokine receptors”, J. Virol., 74 (2000), 11008–11016 | DOI

[45] Pollakis G., Kang S., Kliphuis A., Chalaby M. I., Goudsmit J., Paxton W. A., “N-linked glycosylation of the HIV type-1 gp120 envelope glycoprotein as a major determinant of CCR5 and CXCR4 coreceptor utilization”, J. Biol. Chem., 276 (2001), 13433–13441 | DOI

[46] Polzer S., Dittmar M. T., Schmitz H., Meyer B., Muller H., Krausslich H. G., Schreiber M., “Loss of N-linked glycans in the V3-loop region of gp120 is correlated to an enhanced infectivity of HIV-1”, Glycobiology, 11 (2001), 11–19 | DOI

[47] Basmaciogullari S., Babcock G. J., Van Ryk D., Wojtowicz W., Sodroski J., “Identification of conserved and variable structures in the human immunodeficiency virus gp120 glycoprotein of importance for CXCR4 binding”, J. Virol., 76 (2002), 10791–10800 | DOI

[48] Cormier E. G., Dragic T., “The crown and stem of the V3 loop play distinct roles in human immunodeficiency virus type 1 envelope glycoprotein interactions with the CCR5 coreceptor”, J. Virol., 76 (2002), 8953–8957 | DOI

[49] Cormier E. G., Tran D. N., Yukhayeva L., Olson W. C., Dragic T., “Mapping the determinants of the CCR5 amino-terminal sulfopeptide interaction with soluble human immunodeficiency virus type 1 gp120-CD4 complexes”, J. Virol., 75 (2001), 5541–5549 | DOI

[50] Hoffman T. L., LaBranche C. C., Zhang W., Canziani G., Robinson J., Chaiken I., Hoxie J. A., Doms R. W., “Stable exposure of the coreceptor-binding site in a CD4-independent HIV-1 envelope protein”, Proc. Natl. Acad. Sci. U.S.A, 96 (1999), 6359–6364 | DOI

[51] Huang C. C., Lam S. N., Acharya P., Tang M., Xiang S. H., Hussan S. S., Stanfield R. L., Robinson J., Sodroski J., Wilson I. A., Wyatt R., Bewley C. A., Kwong P. D., “Structures of the CCR5N terminus and of a tyrosine-sulfatedantibody with HIV-1 gp120 and CD4”, Science, 317 (2007), 1930–1934 | DOI

[52] Hu Q., Trent J. O., Tomaras G. D., Wang Z., Murray J. L., Conolly S. M., Navenot J. M., Barry A. P., Greenberg M. L., Peiper S. C., “Identification of Env determinants in V3 that influence the molecular anatomy of CCR5 utilization”, J. Mol. Biol., 302 (2000), 359–375 | DOI

[53] Shimizu N., Haraguchi Y., Takeuchi Y., Soda Y., Kanbe K., Hoshino H., “Changes in and discrepancies between cell tropisms and coreceptor uses of human immunodeficiency virus type 1 induced by single point mutations at the V3 tip of the env protein”, Virology, 259 (1999), 324–333 | DOI

[54] Ivanoff L. A., Looney D. J., McDanal C., Morris J. F., Wong-Staal F., Langlois A. J., Petteway S. R. Jr., Matthews T. J., “Alteration of HIV-1 infectivity and neutralization by a single amino acid replacement in the V3 loop domain”, AIDS Res. Hum. Retroviruses, 7 (1991), 595–603 | DOI

[55] Takeuchi Y., Akutsu M., Murayama K., Shimizu N., Hoshino H., “Host range mutant of human immunodeficiency virus type 1: modification of cell tropism by a single point mutation at the neutralization epitope in the env gene”, J. Virol., 65 (1991), 1710–1718

[56] Ivanoff L. A., Dubay J. W., Morris J. F., Roberts S. J., Gutshall L., Sternberg E. J., Hunter E., Matthews T. J., Petteway S. R. Jr., “V3 loop region of the HIV-1 gp120 envelope protein is essential for virus infectivity”, Virology, 187 (1992), 423–432 | DOI

[57] Grimaila R. J., Fuller B. A., Rennert P. D., Nelson M. B., Hammarskjold M. L., Potts B., Murray M., Putney S. D., Gray G., “Mutations in the principal neutralization determinant of human immunodeficiency virus type 1 affect syncytium formation, virus infectivity, growth kinetics, and neutralization”, J. Virol., 66 (1992), 1875–1883

[58] Nehete P. N., Vela E. M., Hossain M. M., Sarkar A. K., Yahi N., Fantini J., Sastry K. J., “A post-CD4-binding step involving interaction of the V3 region of viral gp120 with host cell surface glycosphingolipids is common to entry and infection by diverse HIV-1 strains”, Antiviral Res., 56 (2002), 233–251 | DOI

[59] Harouse J. M., Bhat S., Spitalnik S. I., Laughlin M., Stefano K., Silberberg D. H., Gonzalez-Scarano F., “Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide”, Science, 253 (1991), 320–323 | DOI

[60] Anischenko I. V., Tuzikov A. V., Andrianov A. M., “Kompyuternyi dizain potentsialnykh lekarstvennykh preparatov dlya terapii SPIDa: $\beta$-galaktoziltseramid i petlya V3 belka gp120 VICh-1”, Matematicheskaya biologiya i bioinformatika, 6:2 (2011), 161–172