Characterization of the mode of action of a potent dengue virus capsid inhibitor

Journal of Virology

Volumn 88, Issue 19, 2014, Pages 11540-11555

  Scaturro, Pietro ^a   Trist, Iuni Margaret Laura ^b   Paul, David ^a   Kumar, Anil ^a,e   Acosta, Eliana G ^a   Byrd, Chelsea M ^c,f   Jordan, Robert ^c,g   Brancale, Andrea ^b   Bartenschlager, Ralf ^a,d  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b CARDIFF UNIVERSITY   (United Kingdom)

^c SIGA Technologies Incorporated   (United States)

^d German Centre for Infection Research   (Germany)

^e UNIVERSITY OF ALBERTA   (Canada)

^f Kineta Inc   (United States)

^g GILEAD SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; CAPSID PROTEIN; ST 148; UNCLASSIFIED DRUG; FUSED HETEROCYCLIC RINGS; ST-148; THIADIAZOLE DERIVATIVE;

ANIMAL CELL; ANTIVIRAL ACTIVITY; ARTICLE; BIOLUMINESCENCE RESONANCE ENERGY TRANSFER; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENGUE VIRUS; DRUG EFFICACY; DRUG POTENCY; DRUG STRUCTURE; FLUORESCENCE MICROSCOPY; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; IMAGING; IMMUNOFLUORESCENCE; IN VITRO STUDY; MOLECULAR DOCKING; MOLECULAR DYNAMICS; NONHUMAN; NUCLEOTIDE SEQUENCE; PROTEIN ASSEMBLY; PROTEIN INTERACTION; PROTEIN STRUCTURE; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA TRANSCRIPTION; SEQUENCE ALIGNMENT; SITE DIRECTED MUTAGENESIS; TRANSMISSION ELECTRON MICROSCOPY; VIRUS CAPSID; VIRUS INFECTIVITY; VIRUS REPLICATION; VIRUS TITRATION; AMINO ACID SEQUENCE; ANIMAL; CHEMISTRY; CHLOROCEBUS AETHIOPS; DRUG ANTAGONISM; DRUG EFFECT; HAMSTER; HEK293 CELL LINE; LIVER CELL; MOLECULAR GENETICS; PHYSIOLOGY; TUMOR CELL LINE; VERO CELL LINE; VIRION; VIROLOGY; VIRUS ASSEMBLY; VIRUS ENTRY; VIRUS RELEASE; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANIMALS; ANTIVIRAL AGENTS; CAPSID; CAPSID PROTEINS; CELL LINE, TUMOR; CERCOPITHECUS AETHIOPS; CRICETINAE; CRYSTALLOGRAPHY, X-RAY; DENGUE VIRUS; HEK293 CELLS; HEPATOCYTES; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; MOLECULAR DOCKING SIMULATION; MOLECULAR SEQUENCE DATA; SEQUENCE ALIGNMENT; THIADIAZOLES; VERO CELLS; VIRION; VIRUS ASSEMBLY; VIRUS INTERNALIZATION; VIRUS RELEASE;

EID: 84906971635     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01745-14     Document Type: Article

References (66)

1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI. 2013. The global distribution and burden of dengue. Nature 496:504-507. http: //dx.doi.org/10.1038/nature12060.
2. Sabchareon A, Wallace D, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S, Jiwariyavej V, Dulyachai W, Pengsaa K, Wartel TA, Moureau A, Saville M, Bouckenooghe A, Viviani S, Tornieporth NG, Lang J. 2012. Protective efficacy of the recombinant, liveattenuated, CYDtetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet 380:1559-1567. http://dx.doi .org/10.1016/S0140-6736(12)61428-7.
3. Nowak T, Farber PM, Wengler G, Wengler G. 1989. Analyses of the terminal sequences of West Nile virus structural proteins and of the in vitro translation of these proteins allow the proposal of a complete scheme of the proteolytic cleavages involved in their synthesis. Virology 169:365-376. http://dx.doi.org/10.1016/0042-6822(89)90162-1.
4. Gollins SW, Porterfield JS. 1986. The uncoating and infectivity of the flavivirus West Nile on interaction with cells: effects of pH and ammonium chloride. J. Gen. Virol. 67(Part 9):1941-1950. http://dx.doi.org/10 .1099/0022-1317-67-9-1941.
5. Heinz FX, Stiasny K, Puschner-Auer G, Holzmann H, Allison SL, Mandl CW, Kunz C. 1994. Structural changes and functional control of the tick-borne encephalitis virus glycoprotein E by the heterodimeric association with protein prM. Virology 198:109-117. http://dx.doi.org/10 .1006/viro.1994.1013.
6. Paul D, Bartenschlager R. 2013. Architecture and biogenesis of plusstrand RNA virus replication factories. World J. Virol. 2:32-48. http://dx .doi.org/10.5501/wjv.v2.i2.32.
7. Belov GA, van Kuppeveld FJ. 2012. (+)RNA viruses rewire cellular pathways to build replication organelles. Curr. Opin. Virol. 2:740-747. http://dx.doi.org/10.1016/j.coviro.2012.09.006.
8. Junjhon J, Pennington JG, Edwards TJ, Perera R, Lanman J, Kuhn RJ. 2014. Ultrastructural characterization and three-dimensional architecture of replication sites in dengue virus-infected mosquito cells. J. Virol. 88: 4687-4697. http://dx.doi.org/10.1128/JVI.00118-14.
9. Welsch S, Miller S, Romero-Brey I, Merz A, Bleck CK, Walther P, Fuller SD, Antony C, Krijnse-Locker J, Bartenschlager R. 2009. Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5:365-375. http://dx.doi.org/10.1016/j .chom.2009.03.007.
10. Jones CT, Ma L, Burgner JW, Groesch TD, Post CB, Kuhn RJ. 2003. Flavivirus capsid is a dimeric alpha-helical protein. J. Virol. 77:7143-7149. http://dx.doi.org/10.1128/JVI.77.12.7143-7149.2003.
11. Wang SH, Syu WJ, Hu ST. 2004. Identification of the homotypic interaction domain of the core protein of dengue virus type 2. J. Gen. Virol. 85:2307-2314. http://dx.doi.org/10.1099/vir.0.80067-0.
12. Ma L, Jones CT, Groesch TD, Kuhn RJ, Post CB. 2004. Solution structure of dengue virus capsid protein reveals another fold. Proc. Natl. Acad. Sci. U. S. A. 101:3414-3419. http://dx.doi.org/10.1073/pnas .0305892101.
13. Byrd CM, Dai D, Grosenbach DW, Berhanu A, Jones KF, Cardwell KB, Schneider C, Wineinger KA, Page JM, Harver C, Stavale E, Tyavanagimatt S, Stone MA, Bartenschlager R, Scaturro P, Hruby DE, Jordan R. 2013. A novel inhibitor of dengue virus replication that targets the capsid protein. Antimicrob. Agents Chemother. 57:15-25. http://dx.doi.org/10 .1128/AAC.01429-12.
14. Angers S, Salahpour A, Joly E, Hilairet S, Chelsky D, Dennis M, Bouvier M. 2000. Detection of beta 2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET). Proc. Natl. Acad. Sci. U. S. A. 97:3684-3689. http://dx.doi.org/10.1073/pnas.97.7 .3684.
15. Samsa MM, Mondotte JA, Iglesias NG, Assuncao-Miranda I, Barbosa-Lima G, Da Poian AT, Bozza PT, Gamarnik AV. 2009. Dengue virus capsid protein usurps lipid droplets for viral particle formation. PLoS Pathog. 5:e1000632. http://dx.doi.org/10.1371/journal.ppat.1000632.
16. Steinmann E, Brohm C, Kallis S, Bartenschlager R, Pietschmann T. 2008. Efficient trans-encapsidation of hepatitis C virus RNAs into infectious virus-like particles. J. Virol. 82:7034-7046. http://dx.doi.org/10 .1128/JVI.00118-08.
17. Fischl W, Bartenschlager R. 2013. High-throughput screening using dengue virus reporter genomes. Methods Mol. Biol. 1030:205-219. http: //dx.doi.org/10.1007/978-1-62703-484-5_17.
18. Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ. 2005. GROMACS: fast, flexible, and free. J. Comput. Chem. 26:1701-1718. http://dx.doi.org/10.1002/jcc.20291.
19. Kumar A, Buhler S, Selisko B, Davidson A, Mulder K, Canard B, Miller S, Bartenschlager R. 2013. Nuclear localization of dengue virus nonstructural protein 5 does not strictly correlate with efficient viral RNA replication and inhibition of type I interferon signaling. J. Virol. 87:4545-4557. http://dx.doi.org/10.1128/JVI.03083-12.
20. Paul D, Romero-Brey I, Gouttenoire J, Stoitsova S, Krijnse-Locker J, Moradpour D, Bartenschlager R. 2011. NS4B self-interaction through conserved C-terminal elements is required for the establishment of functional hepatitis C virus replication complexes. J. Virol. 85:6963-6976. http://dx.doi.org/10.1128/JVI.00502-11.
21. Westaway EG. 1973. Proteins specified by group B togaviruses in mammalian cells during productive infections. Virology 51:454-465. http://dx .doi.org/10.1016/0042-6822(73)90444-3.
22. Kudelko M, Brault JB, Kwok K, Li MY, Pardigon N, Peiris JS, Bruzzone R, Despres P, Nal B, Wang PG. 2012. Class II ADP-ribosylation factors are required for efficient secretion of dengue viruses. J. Biol. Chem. 287: 767-777. http://dx.doi.org/10.1074/jbc.M111.270579.
23. Harvey TJ, Liu WJ, Wang XJ, Linedale R, Jacobs M, Davidson A, Le TT, Anraku I, Suhrbier A, Shi PY, Khromykh AA. 2004. Tetracyclineinducible packaging cell line for production of flavivirus replicon particles. J. Virol. 78:531-538. http://dx.doi.org/10.1128/JVI.78.1.531-538 .2004.
24. Khromykh AA, Kenney MT, Westaway EG. 1998. Transcomplementation of flavivirusRNApolymerase gene NS5 by using Kunjin virus replicon-expressing BHK cells. J. Virol. 72:7270-7279.
25. Gehrke R, Ecker M, Aberle SW, Allison SL, Heinz FX, Mandl CW. 2003. Incorporation of tick-borne encephalitis virus replicons into virus-like particles by a packaging cell line. J. Virol. 77:8924-8933. http://dx.doi.org /10.1128/JVI.77.16.8924-8933.2003.
26. Ansarah-Sobrinho C, Nelson S, Jost CA, Whitehead SS, Pierson TC. 2008. Temperature-dependent production of pseudoinfectious dengue reporter virus particles by complementation. Virology 381:67-74. http: //dx.doi.org/10.1016/j.virol.2008.08.021.
27. Scholle F, Girard YA, Zhao Q, Higgs S, Mason PW. 2004. Transpackaged West Nile virus-like particles: infectious properties in vitro and in infected mosquito vectors. J. Virol. 78:11605-11614. http://dx.doi.org /10.1128/JVI.78.21.11605-11614.2004.
28. Sangiambut S, Keelapang P, Aaskov J, Puttikhunt C, Kasinrerk W, Malasit P, Sittisombut N. 2008. Multiple regions in dengue virus capsid protein contribute to nuclear localization during virus infection. J. Gen. Virol. 89:1254-1264. http://dx.doi.org/10.1099/vir.0.83264-0.
29. Wang SH, Syu WJ, Huang KJ, Lei HY, Yao CW, King CC, Hu ST. 2002. Intracellular localization and determination of a nuclear localization signal of the core protein of dengue virus. J. Gen. Virol. 83:3093-3102.
30. Westaway EG, Khromykh AA, Kenney MT, Mackenzie JM, Jones MK. 1997. Proteins C and NS4B of the flavivirus Kunjin translocate independently into the nucleus. Virology 234:31-41. http://dx.doi.org/10.1006 /viro.1997.8629.
31. Westaway EG, Mackenzie JM, Khromykh AA. 2002. Replication and gene function in Kunjin virus. Curr. Top. Microbiol. Immunol. 267:323-351. http://dx.doi.org/10.1007/978-3-642-59403-8_16.
32. Mackenzie JM, Westaway EG. 2001. Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. J. Virol. 75:10787-10799. http://dx.doi.org/10.1128/JVI.75.22.10787-10799.2001.
33. Bhuvanakantham R, Cheong YK, Ng ML. 2010. West Nile virus capsid protein interaction with importin and HDM2 protein is regulated by protein kinase C-mediated phosphorylation. Microbes Infect. 12:615-625. http://dx.doi.org/10.1016/j.micinf.2010.04.005.
34. Balinsky CA, Schmeisser H, Ganesan S, Singh K, Pierson TC, Zoon KC.2013. Nucleolin interacts with the dengue virus capsid protein and plays a role in formation of infectious virus particles. J. Virol. 87:13094-13106. http://dx.doi.org/10.1128/JVI.00704-13.
35. Xu Z, Anderson R, Hobman TC. 2011. The capsid-binding nucleolar helicase DDX56 is important for infectivity of West Nile virus. J. Virol. 85:5571-5580. http://dx.doi.org/10.1128/JVI.01933-10.
36. Cheong YK, Ng ML. 2011. Dephosphorylation of West Nile virus capsid protein enhances the processes of nucleocapsid assembly. Microbes Infect. 13:76-84. http://dx.doi.org/10.1016/j.micinf.2010.10.014.
37. Mori Y, Okabayashi T, Yamashita T, Zhao Z, Wakita T, Yasui K, Hasebe F, Tadano M, Konishi E, Moriishi K, Matsuura Y. 2005. Nuclear localization of Japanese encephalitis virus core protein enhances viral replication. J. Virol. 79:3448-3458. http://dx.doi.org/10.1128/JVI.79.6.3448 -3458.2005.
38. Bulich R, Aaskov JG. 1992. Nuclear localization of dengue 2 virus core protein detected with monoclonal antibodies. J. Gen. Virol. 73(Part 11): 2999-3003. http://dx.doi.org/10.1099/0022-1317-73-11-2999.
39. Netsawang J, Noisakran S, Puttikhunt C, Kasinrerk W, Wongwiwat W, Malasit P, Yenchitsomanus PT, Limjindaporn T. 2010. Nuclear localization of dengue virus capsid protein is required for DAXX interaction and apoptosis. Virus Res. 147:275-283. http://dx.doi.org/10.1016/j .virusres.2009.11.012.
40. Chang CJ, Luh HW, Wang SH, Lin HJ, Lee SC, Hu ST. 2001. The heterogeneous nuclear ribonucleoprotein K (hnRNP K) interacts with dengue virus core protein. DNA Cell Biol. 20:569-577. http://dx.doi.org /10.1089/104454901317094981.
41. Colpitts TM, Barthel S, Wang P, Fikrig E. 2011. Dengue virus capsid protein binds core histones and inhibits nucleosome formation in human liver cells. PLoS One 6:e24365. http://dx.doi.org/10.1371/journal.pone .0024365.
42. Pfleger KD, Seeber RM, Eidne KA. 2006. Bioluminescence resonance energy transfer (BRET) for the real-time detection of protein-protein interactions. Nat. Protoc. 1:337-345. http://dx.doi.org/10.1038/nprot.2006.52.
43. Baril M, Racine ME, Penin F, Lamarre D. 2009. MAVS dimer is a crucial signaling component of innate immunity and the target of hepatitis C virus NS3/4A protease. J. Virol. 83:1299-1311. http://dx.doi.org/10.1128 /JVI.01659-08.
44. Mercier JF, Salahpour A, Angers S, Breit A, Bouvier M. 2002. Quantitative assessment of beta 1-and beta 2-adrenergic receptor homo-and heterodimerization by bioluminescence resonance energy transfer. J. Biol. Chem. 277:44925-44931. http://dx.doi.org/10.1074/jbc.M205767200.
45. Markoff L, Falgout B, Chang A. 1997. A conserved internal hydrophobic domain mediates the stable membrane integration of the dengue virus capsid protein. Virology 233:105-117. http://dx.doi.org/10.1006/viro .1997.8608.
46. Martins IC, Gomes-Neto F, Faustino AF, Carvalho FA, Carneiro FA, Bozza PT, Mohana-Borges R, Castanho MA, Almeida FC, Santos NC, Da Poian AT. 2012. The disordered N-terminal region of dengue virus capsid protein contains a lipid-droplet-binding motif. Biochem. J. 444: 405-415. http://dx.doi.org/10.1042/BJ20112219.
47. Kuhn RJ, Zhang W, Rossmann MG, Pletnev SV, Corver J, Lenches E, Jones CT, Mukhopadhyay S, Chipman PR, Strauss EG, Baker TS, Strauss JH. 2002. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108:717-725. http://dx.doi.org /10.1016/S0092-8674(02)00660-8.
48. Zhang W, Chipman PR, Corver J, Johnson PR, Zhang Y, Mukhopadhyay S, Baker TS, Strauss JH, Rossmann MG, Kuhn RJ. 2003. Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. Nat. Struct. Biol. 10:907-912. http://dx.doi.org/10.1038 /nsb990.
49. Zhang X, Ge P, Yu X, Brannan JM, Bi G, Zhang Q, Schein S, Zhou ZH. 2013. Cryo-EM structure of the mature dengue virus at 3.5-A resolution. Nat. Struct. Mol. Biol. 20:105-110. http://dx.doi.org/10.1038/nsmb.2463.
50. Klumpp K, Crepin T. 2014. Capsid proteins of enveloped viruses as antiviral drug targets. Curr. Opin. Virol. 5C:63-71. http://dx.doi.org/10 .1016/j.coviro.2014.02.002.
51. Acosta EG, Castilla V, Damonte EB. 2012. Differential requirements in endocytic trafficking for penetration of dengue virus. PLoS One 7:e44835. http://dx.doi.org/10.1371/journal.pone.0044835.
52. van der Schaar HM, Rust MJ, Chen C, Ende-Metselaar H, Wilschut J, Zhuang X, Smit JM. 2008. Dissecting the cell entry pathway of dengue virus by single-particle tracking in living cells. PLoS Pathog. 4:e1000244. http://dx.doi.org/10.1371/journal.ppat.1000244.
53. Delaney WE, Edwards R, Colledge D, Shaw T, Furman P, Painter G, Locarnini S. 2002. Phenylpropenamide derivatives AT-61 and AT-130 inhibit replication of wild-type and lamivudine-resistant strains of hepatitis B virus in vitro. Antimicrob. Agents Chemother. 46:3057-3060. http: //dx.doi.org/10.1128/AAC.46.9.3057-3060.2002.
54. Deres K, Schroder CH, Paessens A, Goldmann S, Hacker HJ, Weber O, Kramer T, Niewohner U, Pleiss U, Stoltefuss J, Graef E, Koletzki D, Masantschek RN, Reimann A, Jaeger R, Gross R, Beckermann B, Schlemmer KH, Haebich D, Rubsamen-Waigmann H. 2003. Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science 299:893-896. http://dx.doi.org/10.1126/science.1077215.
55. King RW, Ladner SK, Miller TJ, Zaifert K, Perni RB, Conway SC, Otto MJ. 1998. Inhibition of human hepatitis B virus replication by AT-61, a phenylpropenamide derivative, alone and in combination with (-)beta-L-2=,3=-dideoxy-3=-thiacytidine. Antimicrob. Agents Chemother. 42: 3179-3186.
56. Perni RB, Conway SC, Ladner SK, Zaifert K, Otto MJ, King RW. 2000. Phenylpropenamide derivatives as inhibitors of hepatitis B virus replication. Bioorg. Med. Chem. Lett. 10:2687-2690. http://dx.doi.org/10.1016 /S0960-894X(00)00544-8.
57. Stray SJ, Bourne CR, Punna S, Lewis WG, Finn MG, Zlotnick A. 2005. A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly. Proc. Natl. Acad. Sci. U. S. A. 102:8138-8143. http: //dx.doi.org/10.1073/pnas.0409732102.
58. Zlotnick A, Ceres P, Singh S, Johnson JM. 2002. A small molecule inhibits and misdirects assembly of hepatitis B virus capsids. J. Virol. 76: 4848-4854. http://dx.doi.org/10.1128/JVI.76.10.4848-4854.2002.
59. Feld JJ, Colledge D, Sozzi V, Edwards R, Littlejohn M, Locarnini SA. 2007. The phenylpropenamide derivative AT-130 blocks HBV replication at the level of viral RNA packaging. Antiviral Res. 76:168-177. http://dx .doi.org/10.1016/j.antiviral.2007.06.014.
60. Katen SP, Chirapu SR, Finn MG, Zlotnick A. 2010. Trapping of hepatitis B virus capsid assembly intermediates by phenylpropenamide assembly accelerators. ACS Chem. Biol. 5:1125-1136. http://dx.doi.org/10.1021 /cb100275b.
61. Fader LD, Bethell R, Bonneau P, Bos M, Bousquet Y, Cordingley MG, Coulombe R, Deroy P, Faucher AM, Gagnon A, Goudreau N, Grand-Maitre C, Guse I, Hucke O, Kawai SH, Lacoste JE, Landry S, Lemke CT, Malenfant E, Mason S, Morin S, O'Meara J, Simoneau B, Titolo S, Yoakim C. 2011. Discovery of a 1,5-dihydrobenzo[1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly. Bioorg. Med. Chem. Lett. 21:398-404. http://dx.doi.org/10.1016/j.bmcl.2010.10.131.
62. Tremblay M, Bonneau P, Bousquet Y, Deroy P, Duan J, Duplessis M, Gagnon A, Garneau M, Goudreau N, Guse I, Hucke O, Kawai SH, Lemke CT, Mason SW, Simoneau B, Surprenant S, Titolo S, Yoakim C. 2012. Inhibition of HIV-1 capsid assembly: optimization of the antiviral potency by site selective modifications at N1, C2 and C16 of a 5-(5-furan-2-yl-pyrazol-1-yl)-1H-benzimidazole scaffold. Bioorg. Med. Chem. Lett. 22:7512-7517. http://dx.doi.org/10.1016/j.bmcl.2012.10.034.
63. Goudreau N, Lemke CT, Faucher AM, Grand-Maitre C, Goulet S, Lacoste JE, Rancourt J, Malenfant E, Mercier JF, Titolo S, Mason SW. 2013. Novel inhibitor binding site discovery on HIV-1 capsid N-terminal domain by NMR and X-ray crystallography. ACS Chem. Biol. 8:1074-1082. http://dx.doi.org/10.1021/cb400075f.
64. Lemke CT, Titolo S, von Schwedler U, Goudreau N, Mercier JF, Wardrop E, Faucher AM, Coulombe R, Banik SS, Fader L, Gagnon A, Kawai SH, Rancourt J, Tremblay M, Yoakim C, Simoneau B, Archambault J, Sundquist WI, Mason SW. 2012. Distinct effects of two HIV-1 capsid assembly inhibitor families that bind the same site within the Nterminal domain of the viral CA protein. J. Virol. 86:6643-6655. http://dx .doi.org/10.1128/JVI.00493-12.
65. Blair WS, Pickford C, Irving SL, Brown DG, Anderson M, Bazin R, Cao J, Ciaramella G, Isaacson J, Jackson L, Hunt R, Kjerrstrom A, Nieman JA, Patick AK, Perros M, Scott AD, Whitby K, Wu H, Butler SL. 2010. HIV capsid is a tractable target for small molecule therapeutic intervention. PLoS Pathog. 6:e1001220. http://dx.doi.org/10.1371/journal.ppat .1001220.
66. Lamorte L, Titolo S, Lemke CT, Goudreau N, Mercier JF, Wardrop E, Shah VB, von Schwedler UK, Langelier C, Banik SS, Aiken C, Sundquist WI, Mason SW. 2013. Discovery of novel small-molecule HIV-1 replication inhibitors that stabilize capsid complexes. Antimicrob. Agents Chemother. 57:4622-4631. http://dx.doi.org/10.1128/AAC.00985-13.