Current Landscape of Antiviral Drug Discovery

F1000Research

Volumn 5, Issue , 2016, Pages

  Blair, Wade ^a   Cox, Christopher ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AK 0529; AL 8176; ALX 0171; ANTIRETROVIRUS AGENT; ANTIVIRUS AGENT; ASVASIRAN; BAY 41 409; CABOTEGRAVIR; ESTERASE INHIBITOR; FAVIPIRAVIR; HETEROARYLDIHYDROPYRIMIDINE DERIVATIVE; INFLUENZA VACCINE; INTEGRASE INHIBITOR; INTERFERON; JNJ 872; MEDI 8897; NUCLEOSIDE ANALOG; OSELTAMIVIR; PALIVIZUMAB; PHENYLPROPENAMIDE; PRESATOVIR; REGN 2222; RIBAVIRIN; RILPIVIRINE; RNA DIRECTED RNA POLYMERASE INHIBITOR; S 033188; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; UNINDEXED DRUG; VIRUS PROTEIN; VX 787;

ANTIVIRAL ACTIVITY; DRUG EFFICACY; DRUG RESEARCH; DRUG TOLERABILITY; HEPATITIS B; HEPATITIS B VIRUS; HIGH RISK PATIENT; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HUMAN RESPIRATORY SYNCYTIAL VIRUS; INFLUENZA; INFLUENZA VIRUS; NONHUMAN; PATIENT COMPLIANCE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RESPIRATORY SYNCYTIAL VIRUS INFECTION; REVIEW; TREATMENT OUTCOME; VIRAL CLEARANCE; VIRUS LOAD;

EID: 84964447027     PISSN: 20461402     EISSN: 1759796X     Source Type: Journal    
DOI: 10.12688/f1000research.7665.1     Document Type: Review

References (57)

1. Ermis F Senocak Tasci E: New treatment strategies for hepatitis C infection. World J Hepatol. 2015;7(17):2100-9. 26301052 10.4254/wjh.v7.i17.2100 4539403
2. Kwon H Lok AS: Hepatitis B therapy. Nat Rev Gastroenterol Hepatol. 2011;8(5):275-84. 21423260 10.1038/nrgastro.2011.33
3. Archin NM Sung JM Garrido C: Eradicating HIV-1 infection: seeking to clear a persistent pathogen. Nat Rev Microbiol. 2014;12(11):750-64. 25402363 10.1038/nrmicro3352 4383747
4. Low-Beer S Yip B O'Shaughnessy MV: Adherence to triple therapy and viral load response. J Acquir Immune Defic Syndr. 2000;23(4):360-1. 10836763 10.1097/00126334-200004010-00014
5. Margolis DA Boffito M: Long-acting antiviral agents for HIV treatment. Curr Opin HIV AIDS. 2015;10(4):246-52. 26049949 10.1097/COH.0000000000000169 F1000 Recommendation
6. https://www.viivhealthcare.com/media/press-releases/2015/november/viiv-healthcare-announces-positive-headline-results-from-a-study-of-two-drug-injectable-regimen-for-hiv-maintenance-therapy.aspx.
7. Williams J Sayles HR Meza JL: Long-acting parenteral nanoformulated antiretroviral therapy: interest and attitudes of HIV-infected patients. Nanomedicine (Lond). 2013;8(11):1807-13. 23611617 10.2217/nnm.12.214 3987826
8. Klumpp K Crépin T: Capsid proteins of enveloped viruses as antiviral drug targets. Curr Opin Virol. 2014;5:63-71. 24607800 10.1016/j.coviro.2014.02.002
9. Bourne CR Finn MG Zlotnick A: Global structural changes in hepatitis B virus capsids induced by the assembly effector HAP1. J Virol. 2006;80(22):11055-61. 16943288 10.1128/JVI.00933-06 1642186 F1000 Recommendation
10. Stray SJ Bourne CR Punna S: A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly. Proc Natl Acad Sci U S A. 2005;102(23):8138-43. 15928089 10.1073/pnas.0409732102 1149411 F1000 Recommendation
11. Katen SP Chirapu SR Finn MG: Trapping of hepatitis B virus capsid assembly intermediates by phenylpropenamide assembly accelerators. ACS Chem Biol. 2010;5(12):1125-36. 20845949 10.1021/cb100275b 3003741 F1000 Recommendation
12. Weber O Schlemmer K Hartmann E: Inhibition of human hepatitis B virus (HBV) by a novel non-nucleosidic compound in a transgenic mouse model. Antiviral Res. 2002;54(2):69-78. 12062392 10.1016/S0166-3542(01)00216-9
13. Brezillon N Brunelle MN Massinet H: Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice. PLoS One. 2011;6(12):e25096. 22162746 10.1371/journal.pone.0025096 3230577 F1000 Recommendation
14. Katen SP Tan Z Chirapu SR: Assembly-directed antivirals differentially bind quasiequivalent pockets to modify hepatitis B virus capsid tertiary and quaternary structure. Structure. 2013;21(8):1406-16. 23871485 10.1016/j.str.2013.06.013 3756818 F1000 Recommendation
15. Wang YJ Lu D Xu YB: A novel pyridazinone derivative inhibits hepatitis B virus replication by inducing genome-free capsid formation. Antimicrob Agents Chemother. 2015;59(11):7061-72. 26349829 10.1128/AAC.01558-15 4604411
16. Klumpp K Shimada T Allweiss L: O115: High antiviral activity of the HBV core inhibitor NVR 3-778 in the humanized uPA/SCID mouse model. J Hepatol. 2015;62(Supplement 2):S250. 10.1016/s0168-8278(15)30134-3
17. De Palma AM Vliegen I De Clercq E: Selective inhibitors of picornavirus replication. Med Res Rev. 2008;28(6):823-84. 18381747 10.1002/med.20125
18. Byrd CM Dai D Grosenbach DW: A novel inhibitor of dengue virus replication that targets the capsid protein. Antimicrob Agents Chemother. 2013;57(1):15-25. 23070172 10.1128/AAC.01429-12 3535982
19. http://www.cdc.gov/flu/about/season/flu-season-2014-2015.htm.
20. Costello HM Ray WC Chaiwatpongsakorn S: Targeting RSV with vaccines and small molecule drugs. Infect Disord Drug Targets. 2012;12(2):110-28. 22335496 10.2174/187152612800100143 3835183
21. Swanson KA Settembre EC Shaw CA: Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers. Proc Natl Acad Sci U S A. 2011;108(23):9619-24. 21586636 10.1073/pnas.1106536108 3111287 F1000 Recommendation
22. Malykhina O Yednak MA Collins PL: A respiratory syncytial virus replicon that is noncytotoxic and capable of long-term foreign gene expression. J Virol. 2011;85(10):4792-801. 21389127 10.1128/JVI.02399-10 3126208 F1000 Recommendation
23. Plant H Stacey C Tiong-Yip CL: High-Throughput Hit Screening Cascade to Identify Respiratory Syncytial Virus (RSV) Inhibitors. J Biomol Screen. 2015;20(5):597-605. 25656237 10.1177/1087057115569428 F1000 Recommendation
24. Mackman RL Sangi M Sperandio D: Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study. J Med Chem. 2015;58(4):1630-43. 25574686 10.1021/jm5017768
25. Wang G Deval J Hong J: Discovery of 4'-chloromethyl-2'-deoxy-3',5'-di- O-isobutyryl-2'-fluorocytidine (ALS-8176), a first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection. J Med Chem. 2015;58(4):1862-78. 25667954 10.1021/jm5017279
26. DeVincenzo JP Whitley RJ Mackman RL: Oral GS-5806 activity in a respiratory syncytial virus challenge study. N Engl J Med. 2014;371(8):711-22. 25140957 10.1056/NEJMoa1401184 F1000 Recommendation
27. DeVincenzo JP McClure MW Symons JA: Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study. N Engl J Med. 2015;373(21):2048-58. 26580997 10.1056/NEJMoa1413275 F1000 Recommendation
28. http://www.aliosbiopharma.com/pipeline/overview/.
29. https://clinicaltrials.gov/ct2/show/NCT02460016.
30. Fodor E: The RNA polymerase of influenza a virus: mechanisms of viral transcription and replication. Acta Virol. 2013;57(2):113-22. 23600869
31. Pflug A Guilligay D Reich S: Structure of influenza A polymerase bound to the viral RNA promoter. Nature. 2014;516(7531):355-60. 25409142 10.1038/nature14008 F1000 Recommendation
32. Reich S Guilligay D Pflug A: Structural insight into cap-snatching and RNA synthesis by influenza polymerase. Nature. 2014;516(7531):361-6. 25409151 10.1038/nature14009 F1000 Recommendation
33. Hengrung N El Omari K Serna Martin I: Crystal structure of the RNA-dependent RNA polymerase from influenza C virus. Nature. 2015;527(7576):114-7. 26503046 10.1038/nature15525 F1000 Recommendation
34. Baranovich T Wong SS Armstrong J: T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J Virol. 2013;87(7):3741-51. 23325689 10.1128/JVI.02346-12 3624194 F1000 Recommendation
35. Oestereich L Lüdtke A Wurr S: Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res. 2014;105:17-21. 24583123 10.1016/j.antiviral.2014.02.014 F1000 Recommendation
36. Smither SJ Eastaugh LS Steward JA: Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model. Antiviral Res. 2014;104:153-5. 24462697 10.1016/j.antiviral.2014.01.012 F1000 Recommendation
37. http://www.msf.org/article/preliminary-results-jiki-clinical-trial-test-efficacy-favipiravir-reducing-mortality.
38. Smith M Klumpp KG: 4'-Difluoromethyl Substituted Nucleoside Derivatives as Inhibitors of Influenza RNA Replication. WO 2015/120237A2.2015. Reference Source
39. Clark MP Ledeboer MW Davies I: Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J Med Chem. 2014;57(15):6668-78. 25019388 10.1021/jm5007275 F1000 Recommendation
40. http://investors.vrtx.com/releasedetail.cfm?releaseid=744857.
41. Byrn RA Jones SM Bennett HB: Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit. Antimicrob Agents Chemother. 2015;59(3):1569-82. 25547360 10.1128/AAC.04623-14 4325764 F1000 Recommendation
42. Tomassini J Selnick H Davies ME: Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds. Antimicrob Agents Chemother. 1994;38(12):2827-37. 7695269 10.1128/AAC.38.12.2827 188292
43. DuBois RM Slavish PJ Baughman BM: Structural and biochemical basis for development of influenza virus inhibitors targeting the PA endonuclease. PLoS Pathog. 2012;8(8):e1002830. 22876176 10.1371/journal.ppat.1002830 3410894
44. Kowalinski E Zubieta C Wolkerstorfer A: Structural analysis of specific metal chelating inhibitor binding to the endonuclease domain of influenza pH1N1 (2009) polymerase. PLoS Pathog. 2012;8(8):e1002831. 22876177 10.1371/journal.ppat.1002831 3410856
45. http://www.shionogi.co.jp/en/ir/pdf/e_p151030.pdf.
46. https://clinicaltrials.gov/ct2/show/NCT02588521.
47. Throsby M van den Brink E Jongeneelen M: Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM + memory B cells. PLoS One. 2008;3(12):e3942. 19079604 10.1371/journal.pone.0003942 2596486 F1000 Recommendation
48. Ekiert DC Bhabha G Elsliger MA: Antibody recognition of a highly conserved influenza virus epitope. Science. 2009;324(5924):246-51. 19251591 10.1126/science.1171491 2758658 F1000 Recommendation
49. Ekiert DC Friesen RH Bhabha G: A highly conserved neutralizing epitope on group 2 influenza A viruses. Science. 2011;333(6044):843-50. 21737702 10.1126/science.1204839 3210727
50. Sui J Hwang WC Perez S: Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol. 2009;16(3):265-73. 19234466 10.1038/nsmb.1566 2692245 F1000 Recommendation
51. Corti D Voss J Gamblin SJ: A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science. 2011;333(6044):850-6. 21798894 10.1126/science.1205669 F1000 Recommendation
52. Wrammert J Koutsonanos D Li GM: Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med. 2011;208(1):181-93. 21220454 10.1084/jem.20101352 3023136 F1000 Recommendation
53. Dreyfus C Laursen NS Kwaks T: Highly conserved protective epitopes on influenza B viruses. Science. 2012;337(6100):1343-8. 22878502 10.1126/science.1222908 3538841 F1000 Recommendation
54. Nakamura G Chai N Park S: An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza A antibodies. Cell Host Microbe. 2013;14(1):93-103. 23870317 10.1016/j.chom.2013.06.004 F1000 Recommendation
55. DiLillo DJ Tan GS Palese P: Broadly neutralizing hemagglutinin stalk-specific antibodies require FcγR interactions for protection against influenza virus in vivo. Nat Med. 2014;20(2):143-51. 24412922 10.1038/nm.3443 3966466 F1000 Recommendation
56. http://www.visterrainc.com/pdfs/2015 1005 Visterra Phase 2a Challenge.pdf.
57. Bedard KM Wang ML Proll SC: Isoflavone agonists of IRF-3 dependent signaling have antiviral activity against RNA viruses. J Virol. 2012;86(13):7334-44. 22532686 10.1128/JVI.06867-11 3416323 F1000 Recommendation