Computer-Aided Search for Novel Anti-Hiv-1 Agents Presenting Peptidomimetics of Neutralizing Antibodies and Evaluation of their Potential Inhibitory Activity by Molecular Modeling

A. M. Andrianov ; I. A. Kashin ; A. V. Tuzikov

Matematičeskaâ biologiâ i bioinformatika, Tome 8 (2013) no. 1, pp. 119-134.

Résumé

Based on the analysis of the structural complexes between the HIV-1 V3 loop peptides from different viral modifications and the Fab-fragment of a broadly neutralizing monoclonal antibody (mAb) 3074, computer-aided search for chemical compounds able to imitate the pharmacophore properties of the antigen-binding site of this antibody was carried out. Evaluation of the binding efficacy of these compounds to the V3 loop peptides was performed by molecular docking followed by selection of the most probable peptidomimetics of mAb 3074. Using molecular dynamics and free energy calculations, it was shown that, similarly to mAb 3074, the selected compounds exhibit a high affinity to the immunogenic tip of the HIV-1 V3 loop forming conserved structural motif, which contains residues critical for cell tropism. In this context, these compounds are considered as the promising basic structures for the design of novel, potent and broad anti-HIV-1 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] Sirois S., Touaibia M., Chou K. C., Roy R., “Glycosylation of HIV-1 gp120 V3 loop: towards the rational design of a synthetic carbohydrate vaccine”, Curr. Med. Chem., 14 (2007), 3232–3242 | DOI

[4] Andrianov A. M., “HIV-1 gp120 V3 loop for anti-AIDS drug discovery: computer-aided approaches to the problem solving”, Expert Opin. Drug Discov., 6 (2011), 419–435 | DOI

[5] Kwong P. D., Doyle M. L., Casper D. J., Cicala C., Leavitt S. A., Majeed S., Steenbeke T. D., Venturi M., Chaiken I., Fung M., Katinger H., Parren P. W., Robinson J., Van Ryk D., Wang L., Burton D. R., Freire E., Wyatt R., Sodroski J., Hendrickson W. A., Arthos J., “HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites”, Nature, 420 (2002), 678–682 | DOI

[6] Chen B., Vogan E. M., Gong H., Skehel J. J., Wiley D. C., Harrison S. C., “Structure of an unliganded simian immunodeficiency virus gp120 core”, Nature, 433 (2005), 834–841 | DOI

[7] Kwong P. D., Wyatt R., Robinson J., Sweet R. W., Sodroski J., Hendrickson W. A., “Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody”, Nature, 393 (1998), 648–659 | DOI

[8] 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

[9] Trkola A., Dragic T., Arthos J., Binlay J. M., Olson W. C., Allaway G. P., Cheng-Meyer C., Robinson J., Maddon P. J., Moore J. P., “CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5”, Nature, 384 (1996), 184–187 | DOI

[10] Wu L., Gerard N. P., Wyatt R., Choe H., Parolin C., Ruffing N., Borsetti A., Cardoso A. A., Desjardin E., Newman W., Gerard C., Sodroski J., “CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5”, Nature, 384 (1996), 179–183 | DOI

[11] Dubay J. W., Roberts S. J., Brody B., Hunter E., “Mutations in the leucine zipper of the human immunodeficiency virus type 1 transmembrane glycoprotein affect fusion and infectivity”, J. Virol., 66 (1992), 4748–4756

[12] Wild C., Dubay J. W., Greenwell T., Baird Jr. T., Oas T. G., McDanal C., Hunter E., Matthews T., “Propensity for a leucine zipper-like domain of human immunodeficiency virus type 1 gp41 to form oligomers correlates with a role in virus-induced fusion rather than assembly of the glycoprotein complex”, Proc. Natl. Acad. Sci. U.S.A., 91 (1994), 12676–12680 | DOI

[13] Looney D. J., Fisher A. G., Putney S. D., Rusche J. R., Redfield R. R., Burke D. S., Gallo R. C., Wong-Staal F., “Type-restricted neutralization of molecular clones of human immunodeficiency virus”, Science, 241 (1988), 357–359 | DOI

[14] Meloen R. H., Liskamp R. M., Goudsmit J., “Specificity and function of the individual amino acids of an important determinant of human immunodeficiency virus type 1 that induces neutralizing activity”, J. Gen. Virol., 70 (1989), 1505–1512 | DOI

[15] Hoxie J. A., “Toward an Antibody-Based HIV-1”, Vaccine Annu. Rev. Med., 61 (2010), 135–152 | DOI

[16] Walker L. M., Burton D. R., “Rational antibody-based HIV-1 vaccine design: current approaches and future directions”, Curr. Opin. Immunol., 22 (2010), 358–366 | DOI

[17] Kwong P. D., Mascola J. R., Nabel G. J., “Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to HIV-1”, Cold Spring Harb. Perspect. Med., 2011 | DOI

[18] De Clercq E., “New Approaches toward Anti-HIV Chemotherapy”, J. Med. Chem., 48 (2005), 1297–1313 | DOI

[19] Este J. A., Telenti A., “HIV entry inhibitors”, Lancet, 370 (2007), 81–88 | DOI

[20] Rusconi S., Scozzafava A., Mastrolorenzo A., Supuran C. T., “An update in the development of HIV entry inhibitors”, Curr. Topics in Med. Chem., 7 (2007), 1273–1289 | DOI

[21] Ryser H. J.-P., Fluckiger R., “Progress in targeting HIV-1 entry”, Drug Discov. Today, 10 (2005), 1085–1094 | DOI

[22] Adamson C. S., Freed E. O., “Novel approaches to inhibiting HIV-1 replication”, Antiviral. Res., 85 (2010), 119–141 | DOI

[23] Tilton J. C., Doms R. W., “Entry inhibitors in the treatment of HIV-1 infection”, Antiviral Res., 85 (2010), 91–100 | DOI

[24] Orsega S., “Treatment of adult HIV infection: antiretroviral update and overview”, JNP, 10 (2007), 612–624

[25] Turpin J. A., “The next generation of HIV/AIDS drugs: novel and developmental antiHIV drugs and targets”, Expert Rev. Anti-infect. Ther., 1 (2003), 97–128 | DOI

[26] Vermeire K., Schols D., Bell T. W., “Inhibitors of HIV infection via the cellular CD4 receptor”, Curr. Med. Chem., 13 (2006), 731–743 | DOI

[27] Walker L. M., Phogat S. K., Chan-Hui P. Y., Wagner D., Phung P., Goss J. L., Wrin T., Simek M. D., Fling S., Mitcham J. L., Lehrman J. K., Priddy F. H., Olsen O. A., Frey S. M., Hammond P. W., Kaminsky S., Zamb T., Moyle M., Koff W. C., Poignard P., Burton D. R., “Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target”, Science, 326 (2009), 285–289 | DOI

[28] Wu X., Zhou T., Zhu J., Zhang B., Georgiev I., Wang C., Chen X., Longo N. S., Louder M., McKee K., O'Dell S., Perfetto S., Schmidt S. D., Shi W., Wu L., Yang Y., Yang Z.- Y., Yang Z., Zhang Z., Bonsignori M., Crump J. A., Kapiga S. H., Sam N. E., Haynes B. F., Simek M., Burton D. R., Koff W. C., Doria-Rose N. A., Connors M., Mullikin J. C., Nabel G. J., Roederer M., Shapiro L., Kwong P. D., Mascola J. R., “Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing”, Science, 333 (2011), 1593–1602 | DOI

[29] Klein F., Gaebler C., Mouquet H., Sather D. H., Lehmann C., Scheid J. F., Kraft Z., Liu Y., Pietzsch J., Hurley A., Poignard P., Feizi T., Morris L., Walker B. D., Fatkenheuer G., Seaman M. S., Stamatatos L., Nussenzweig M. C., “Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein”, J. Exp. Med., 209 (2012), 1469–1479 | DOI

[30] Hioe C. E., Wrin T., Seaman M. S., Yu X., Wood B., Self S., Williams C., Gorny M. K., Zolla-Pazner S., “Anti-V3 Monoclonal Antibodies Display Broad Neutralizing Activities against Multiple HIV-1 Subtypes”, PLoS ONE, 5:4 (2010), e10254 | DOI

[31] 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

[32] Floris M., Masciocchi J., Fanton M., Moro S., “Swimming Into Peptidomimetic Chemical Space Using pepMMsMIMIC”, Nucl. Acids Res., 39 (2011), 261–269 | DOI

[33] Bernstein F. C., Koetzle T. F., Williams G. J. B., Meyer E. F., Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M., “The protein data bank. A computer-based archival file for macromolecular structures”, J. Mol. Biol., 112 (1977), 535–542 | DOI

[34] 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

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

[36] Masciocchi J., Frau G., Fanton M., Sturlese M., Floris M., Pireddu L., Palla P., Cedrati F., Rodriguez-Tome P., Moro S., “MMsINC: a large-scale chemoinformatics database”, Nucl. Acids Res., 37 (2009), D284–D290 | DOI

[37] Ballester P. J., Richards W. G., “Ultrafast shape recognition to search compound databases for similar molecular shapes”, J. Comput. Chem., 28 (2007), 1711–1723 | DOI

[38] Mason J. S., Morize I., Menard P. R., Cheney D. L., Hulme C., Labaudiniere R. F., “New 4-point pharmacophore method for molecular similarity and diversity applications: overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures”, J. Med. Chem., 42 (1999), 3251–3264 | DOI

[39] Karnachi P., Kulkarni A., “Application of pharmacophore Engerprints to structure-based design and data mining”, Pharmacophores and Pharmacophore Searches, eds. Langer T., Hoffmannn R. D., Wiley-VCH, Germany, Weinheim, 2006, 193–206 | DOI

[40] 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

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

[42] 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

[43] 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

[44] 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

[45] 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, 170 pp.

[46] 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

[47] 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

[48] 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

[49] 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

[50] 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

[51] 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

[52] 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

[53] 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

[54] 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

[55] 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

[56] 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

[57] 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

[58] Grimaila R. J., Fuller B. A., Rennert P. D., Nelson M. B., Hammarskjöld 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

[59] 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

[60] 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