Virtual Screening of Novel Hiv-1 Entry Inhibitors Blocking Cd4-Binding Site of the Virus Envelope Gp120 Protein

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

Matematičeskaâ biologiâ i bioinformatika, Tome 9 (2014) no. 2, pp. 359-372.

Résumé

Virtual screening of novel anti-HIV agents presenting potential peptidomimetics of cellular receptor CD4 was carried out and evaluation of their inhibitory activity was performed by molecular modeling tools. As a result, five chemical compounds exhibiting, with the designed data, a high affinity to the CD4-binding site of the HIV-1 gp120 protein, which is a functionally conserved epitope of the viral envelope, were identified. In this context, the selected compounds are considered as potential broad-spectrum HIV-1 entry inhibitors.

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] Hu W. S., Hughes S. H., “HIV-1 reverse transcription”, Cold Spring Harb. Perspect. Med., 2:10 (2012), a006882

[6] Miller M. D., Farnet C. M., Bushman F. D., “Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition”, J. Virol., 71:7 (1997), 5382–5390

[7] Engelman A., Cherepanov P., “The structural biology of HIV-1: mechanistic and therapeutic insights”, Nat. Rev. Microbiol., 10:4 (2012), 279–290 | DOI

[8] Wei P., Garber M. E., Fang S. M., Fischer W. H., Jones K. A., “A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA”, Cell, 92:4 (1998), 451–462 | DOI

[9] Zimmerman C., Klein K. C., Kiser P. K., Singh A. R., Firestein B. L., Riba S. C., Lingappa J. R., “Identification of a host protein essential for assembly of immature HIV-1 capsids”, Nature, 415:6867 (2002), 88–92 | DOI

[10] De Clercq E., “New approaches toward anti-HIV chemotherapy”, J. Med. Chem., 48 (2005), 1297–1313 | DOI

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

[12] 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

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

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

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

[16] Arts E. J., Hazuda D. J., “HIV-1 antiretroviral drug therapy”, Cold Spring Harb. Perspect. Med., 2:4 (2012), a007161 | DOI

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

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

[19] Este J. A., Telenti A., “HIV entry inhibitors”, Lancet, 370:9581 (2007), 81–88 | DOI

[20] Lin P.-F., Blair W., Wang T., Spicer T., Guo Q., Zhou N., Gong Y.-F., Wang H.-G. H., Rose R., Yamanaka G., Robinson B., Li C.-B., Fridell R., Deminie C., Demers G., Yang Z., Zadjura L., Meanwell N., Colonno R., “A small molecule HIV-1 inhibitor that targets the HIV-1 envelope and inhibits CD4 receptor binding”, Proc. Natl. Acad. Sci. USA, 100:19 (2003), 11013–11018 | DOI

[21] Reimann K. A., Lin W., Bixler S., Browning B., Ehrenfels B. N., Lucci J., Miatkowski K., Olson D., Parish T. H., Rosa M. D., Oleson F. B., Hsu Y. M., Padlan E. A., Letvin N. L., Burkly L. C., “A humanized form of a CD4-specific monoclonal antibody exhibits decreased antigenicity and prolonged plasma half-life in rhesus monkeys while retaining its unique biological and antiviral properties”, AIDS Res. Hum. Retroviruses, 13:11 (1997), 933–943 | DOI

[22] Lalezari J. P., Henry K., O'Hearn M., Montaner J. S. G., Piliero P. J., Trottier B., Walmsley S., Cohen C., Kuritzkes D. R., Eron J. J., Chung J., DeMasi R., Donatacci L., Drobnes C., Delehanty J., Salgo M., “Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America”, N. Engl. J. Med., 348:22 (2003), 2175–2185 | DOI

[23] Duffalo M. L., James C. W., “Enfuvirtide: a novel agent for the treatment of HIV-1 infection”, Ann. Pharmacother., 37 (2003), 1448–1456 | DOI

[24] Hardy H., Skolnik P. R., “Enfuvirtide, a new fusion inhibitor for therapy of human immunodeficiency virus infection”, Pharmacotherapy, 24 (2004), 198–211 | DOI

[25] Dragic T., Trkola A., Thompson D. A. D., Cormier E. G., Kajumo F. A., Maxwell E., Lin S. W., Ying W., Smith S. O., Sakmar T. P., Moore J. P., “A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5”, Proc. Natl. Acad. Sci. USA, 97:10 (2000), 5639–5644 | DOI

[26] Tsamis F., Gavrilov S., Kajumo F., Seibert C., Kuhmann S., Ketas T., Trkola A., Palani A., Clader J. W., Tagat J. R., McCombie S., Baroudy B., Moore J. P., Sakmar T. P., Dragic T., “Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH-351125 and SCH-350581 inhibit human immunodeficiency virus type 1 entry”, J. Virol., 77:9 (2003), 5201–5208 | DOI

[27] Meanwell N. A., Kadow J. F., “Maraviroc, a chemokine CCR5 receptor antagonist for the treatment of HIV infection and AIDS”, Curr. Opin. Investig. Drugs., 8 (2007), 669–681

[28] Briz V., Poveda E., Soriano V., “HIV entry inhibitors: mechanisms of action and resistance pathways”, J. Antimicrob. Chemother., 57 (2006), 619–627 | DOI

[29] Haim H., Si Z., Madani N., Wang L., Courter J. R., Princiotto A., Kassa A., DeGrace M., McGee-Estrada K., Mefford M., Dana Gabuzda D., Smith A. B., Sodroski1 J., “Soluble CD4 and CD4-mimetic compounds inhibit HIV-1 infection by induction of a short-lived activated state”, PLoS Pathog., 5:4 (2009), e1000360 | DOI

[30] Curreli F., Choudhury S., Pyatkin I,, Zagorodnikov V. P., Bulay A. K., Altieri A., Do Kwon Y., Kwong P. D., Debnath A. K., “Design, synthesis and antiviral activity of entry inhibitors that target the CD4-binding site of HIV-1”, J. Med. Chem., 55 (2012), 4764–4775 | DOI

[31] 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

[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] 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

[34] 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

[35] 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

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

[37] 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

[38] 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

[39] 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

[40] 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. K., 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

[41] 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

[42] 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

[43] Ryckaert J. P., Ciccotti G., Berendsen H. J. C., “Numerical integration of the Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes”, J. Comput. Phys., 23 (1977), 327–341 | 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] Durranta J. D., McCammon J. A., “BINANA: A novel algorithm for ligand-binding characterization”, J. Mol. Graph. Model., 29 (2011), 888–893 | DOI

[46] McDonald I. K., Thornton J. M., “Satisfying hydrogen bonding potential in proteins”, J. Mol. Biol., 238 (1994), 777–793 | DOI

[47] 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.

[48] Myszka D. G., Sweet R. W., Hensley P., Brigham-Burke M., Kwong P. D., Hendrickson W. A., Wyatt R., Sodroski J., Doyle M. L., “Energetics of the HIV gp120-CD4 binding reaction”, Proc. Natl. Acad. Sci. USA, 97 (2000), 9026–9031 | DOI

[49] Lipinski C. A., Lombardo F., Dominy B. W., Feeney P. J., “Lead- and drug-like compounds: the rule-of-five revolution”, Adv. Drug Delivery Rev., 46 (2001), 3–26 | DOI