Antivirals targeting the polymerase complex of influenza viruses

Antiviral Research

Volumn 169, Issue , 2019, Pages

  Mifsud, Edin J ^a   Hayden, Frederick G ^b   Hurt, Aeron C ^a,c  

^a VICTORIAN INFECTIOUS DISEASES REFERENCE LABORATORY   (Australia)

^b UNIVERSITY OF VIRGINIA   (United States)

^c UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AL 794; ANTIVIRUS AGENT; BALOXAVIR; BALOXAVIR MARBOXIL; ENZYME INHIBITOR; FAVIPIRAVIR; OSELTAMIVIR; PIMODIVIR; RIMANTADINE; SIALIDASE INHIBITOR; UNCLASSIFIED DRUG; AMIDE; DNA DIRECTED RNA POLYMERASE; OXAZINE DERIVATIVE; PYRAZINE DERIVATIVE; PYRIDINE DERIVATIVE; SERINE PROTEINASE; SFERICASE; SIALIDASE; THIEPIN DERIVATIVE; TRIAZINE DERIVATIVE;

AMINO ACID SUBSTITUTION; ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; CLINICAL EFFECTIVENESS; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; HUMAN; INFLUENZA; INFLUENZA VIRUS; NONHUMAN; PRIORITY JOURNAL; REVIEW; DRUG COMBINATION; DRUG EFFECT; INFLUENZA A VIRUS; INFLUENZA B VIRUS; ORTHOMYXOVIRIDAE;

AMIDES; ANTIVIRAL AGENTS; DNA-DIRECTED RNA POLYMERASES; DRUG COMBINATIONS; DRUG RESISTANCE, VIRAL; ENZYME INHIBITORS; HUMANS; INFLUENZA A VIRUS; INFLUENZA B VIRUS; NEURAMINIDASE; ORTHOMYXOVIRIDAE; OSELTAMIVIR; OXAZINES; PYRAZINES; PYRIDINES; SERINE ENDOPEPTIDASES; THIEPINS; TRIAZINES;

EID: 85067841826     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2019.104545     Document Type: Review

References (91)

1. Adisasmito, W., Chan, P.K.S., Lee, N., et al. Effectiveness of antiviral treatment in human influenza A(H5N1) infections: analysis of a global patient registry. J. Infect. Dis. 202:8 (2010), 1154–1160.
2. Allen, U.D., Aoki, F.Y., Stiver, H.G., The use of antiviral drugs for influenza: recommended guidelines for practitioners. Can. J. Infect Dis. Med. Microbiol. 17:5 (2006), 273–284.
3. Baranovich, T., Wong, S.-S., Armstrong, J., et al. T-705 (favipiravir) induces lethal mutagenesis in influenza a H1N1 viruses in vitro. J. Virol. 87:7 (2013), 3741–3751.
4. Baz, M., Carbonneau, J., Rhéaume, C., et al. Combination therapy with oseltamivir and favipiravir delays mortality but does not prevent oseltamivir resistance in immunodeficient mice infected with pandemic A(H1N1) influenza virus. Viruses, 10(11), 2018, 610.
5. Bloom, J.D., Gong, L.I., Baltimore, D., Permissive secondary mutations enable the evolution of influenza oseltamivir resistance. Science (New York, N.Y.) 328:5983 (2010), 1272–1275.
6. Byrn, R.A., Jones, S.M., Bennett, H.B., et al. Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit. Antimicrob. Agents Chemother. 59:3 (2015), 1569–1582.
7. Clark, M.P., Ledeboer, M.W., Davies, I., et al. Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J. Med. Chem. 57:15 (2014), 6668–6678.
8. Deleu, S., Kakuda, T.N., Spittaels, K., et al. Single- and multiple-dose pharmacokinetics and safety of pimodivir, a novel, non-nucleoside polymerase basic protein 2 subunit inhibitor of the influenza A virus polymerase complex, and interaction with oseltamivir: a Phase 1 open-label study in healthy volunteers. Br. J. Clin. Pharmacol. 84:11 (2018), 2663–2672.
9. Democratis, J., Pareek, M., Stephenson, I., Use of neuraminidase inhibitors to combat pandemic influenza. J. Antimicrob. Chemother. 58:5 (2006), 911–915.
10. Deyde, V.M., Xu, X., Bright, R.A., et al. Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide. J. Infect. Dis. 196:2 (2007), 249–257.
11. Dobson, J., Whitley, R.J., Pocock, S., et al. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. The Lancet 385:9979 (2015), 1729–1737.
12. Epstein, C., Experience with favipiravir in phase 3 and implications for future studies. 5th Isirv-AVG Conference; Prevention and Treatment of RVIs: Antivirals, Traditional Therapies and Host-Directed Interventions, 2017 (Shanghai, China).
13. Finberg, R.W., Lanno, R., Anderson, D., et al. Phase 2b study of pimodivir (JNJ-63623872) as monotherapy or in combination with oseltamivir for treatment of acute uncomplicated seasonal influenza A: TOPAZ trial. J. Infect. Dis 219:7 (2018), 1026–1034.
14. Fodor, E., Pritlove, D.C., Brownlee, G.G., The influenza virus panhandle is involved in the initiation of transcription. J. Virol. 68:6 (1994), 4092–4096.
15. Fry, A.M., Goswami, D., Nahar, K., et al. Efficacy of oseltamivir treatment started within 5 days of symptom onset to reduce influenza illness duration and virus shedding in an urban setting in Bangladesh: a randomised placebo-controlled trial. Lancet Infect. Dis. 14:2 (2014), 109–118.
16. Fukao, K., Noshi, T., Yamamoto, A., et al. Combination treatment with the cap-dependent endonuclease inhibitor baloxavir marboxil and a neuraminidase inhibitor in a mouse model of influenza A virus infection. J. Antimicrob. Chemother. 74:3 (2019), 654–662.
17. Furuta, Y., Komeno, T., Nakamura, T., Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc. Jpn. Acad. B 93:7 (2017), 449–463.
18. Furuta, Y., Takahashi, K., Kuno-Maekawa, M., et al. Mechanism of action of T-705 against influenza virus. Antimicrob. Agents Chemother. 49:3 (2005), 981–986.
19. Goldhill, D.H., Langat, P., Xie, H., et al. Determining the mutation bias of favipiravir in influenza using next-generation sequencing. J. Virol. 93:2 (2018), e01217–01218.
20. Goldhill, D.H., te Velthuis, A.J.W., Fletcher, R.A., et al. The mechanism of resistance to favipiravir in influenza. Proc. Natl. Acad. Sci. Unit. States Am. 115:45 (2018), 11613–11618.
21. Goto, H., Sakai-Tagawa, Y., Shiraishi, K., et al. High frequency of resistant viruses harboring different mutations in amantadine-treated children with influenza. J. Infect. Dis. 188:1 (2003), 57–61.
22. Gubareva, L.V., Mishin, V.P., Patel, M.C., et al. Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons. Euro Surveill., 24(3), 2019, 1800666.
23. Hall, C.B., Dolin, R., Gala, C.L., et al. Children with influenza a infection: treatment with rimantadine. Pediatrics 80:2 (1987), 275–282.
24. Hay, A.J., Sweet, C., Hayden, F.G., et al. Virulence of rimantadine-resistant human influenza a (H3N2) viruses in ferrets. J. Infect. Dis. 164:5 (1991), 969–972.
25. Hayden, F.G., Belshe, R.B., Clover, R.D., et al. Emergence and apparent transmission of rimantadine-resistant influenza a virus in families. N. Engl. J. Med. 321:25 (1989), 1696–1702.
26. Hayden, F.G., Shindo, N., Influenza virus polymerase inhibitors in clinical development. Curr. Opin. Infect. Dis. 32:2 (2019), 176–186.
27. Hayden, F.G., Sperber, S.J., Belshe, R.B., et al. Recovery of drug-resistant influenza A virus during therapeutic use of rimantadine. Antimicrob. Agents Chemother. 35:9 (1991), 1741–1747.
28. Hayden, F.G., Sugaya, N., Hirotsu, N., et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N. Engl. J. Med. 379:10 (2018), 913–923.
29. Hurt, A.C., Besselaar, T.G., Daniels, R.S., et al. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2014-2015. Antivir. Res. 132 (2016), 178–185.
30. Hurt, A.C., Ernest, J., Deng, Y.-M., et al. Emergence and spread of oseltamivir-resistant A(H1N1) influenza viruses in oceania, south east Asia and South Africa. Antivir. Res. 83:1 (2009), 90–93.
31. Ison, M.G., Portsmouth, S., Yoshida, Y., et al. Phase 3 Trial of Baloxavir Marboxil in High Risk Influenza Patients (CAPSTONE-2 Study). ID Week Advancing Science Week San Francisco. 2018.
32. Jekle, A., Stoycheva, A., Hendricks, R.T., et al. Preclinical antiviral activity and ADME characteristics of the novel influenza endonuclease inhibitor AL-794. Options IX meeting. Annual Scientific Conference for International Society for Influenza and Respiratory and Viral Disease, 2016 (Chicago).
33. Jones, J.C., Susceptibility of Influenza Viruses to the Novel Cap-dependent Endonuclease Inhibitor Baloxavir Marboxil 6th Advances in Respiratory Virus Therapeutics. 2018 (Washington).
34. Kawaguchi, N., Koshimichi, H., Ishibashi, T., et al. Evaluation of drug–drug interaction potential between baloxavir marboxil and oseltamivir in healthy subjects. Clin. Drug Investig. 38:11 (2018), 1053–1060.
35. Kawai, N., Ikematsu, H., Iwaki, N., et al. A comparison of the effectiveness of oseltamivir for the treatment of influenza a and influenza B: a Japanese multicenter study of the 2003–2004 and 2004–2005 influenza seasons. Clin. Infect. Dis. 43:4 (2006), 439–444.
36. Kawamura, K., Hirotsu, N., Iwaki, N., et al. Clinical effectiveness of oseltamivir and zanamivir for treatment of influenza a virus subtype H1N1 with the H274Y mutation: a Japanese, multicenter study of the 2007–2008 and 2008–2009 influenza seasons. Clin. Infect. Dis. 49:12 (2009), 1828–1835.
37. Kiso, M., Mitamura, K., Sakai-Tagawa, Y., et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. The Lancet 364:9436 (2004), 759–765.
38. Kiso, M., Yamashita, M., Ito, M., et al. Combination therapy with neuraminidase and polymerase inhibitors in nude mice infected with influenza virus. J. Infect. Dis. 217:6 (2017), 887–896.
39. Kobayashi, O., Noto, M., Sakurai, T., et al. T-705, a novel anti-influenza virus compound - the safety, tolerability and pharmacokinetics in human. Int. J. Infect. Dis., 12, 2008, e299.
40. Koshimichi, H., Ishibashi, T., Kawaguchi, N., et al. Safety, tolerability, and pharmacokinetics of the novel anti-influenza agent baloxavir marboxil in healthy adults: phase I study findings. Clin. Drug Investig. 38:12 (2018), 1189–1196.
41. Koszalka, P., Tilmanis, D., Roe, M., et al. Baloxavir marboxil susceptibility of influenza viruses from the Asia-Pacific, 2012–2018. Antivir. Res. 164 (2019), 91–96.
42. Krammer, F., Smith, G.J.D., Fouchier, R.A.M., et al. Influenza. Nat. Rev. Dis. Prim., 4(1), 2018, 3.
43. Krug, R.M., Broni, B.A., Bouloy, M., Are the 5′ ends of influenza viral mrnas synthesized in vivo donated by host mRNAs?. Cell 18:2 (1979), 329–334.
44. Lackenby, A., Besselaar, T.G., Daniels, R.S., et al. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors and status of novel antivirals, 2016–2017. Antivir. Res. 157 (2018), 38–46.
45. Lamb, R.A., Choppin, P.W., The gene structure and replication of influenza virus. Annu. Rev. Biochem. 52:1 (1983), 467–506.
46. Leopold, L., Hospital Recovery Scale- the Pimodivir Experience with an Ordinal Scale 6th ISIRV AVS Conference. 2018 (Washington, USA).
47. Lina, B., Boucher, C., Osterhaus, A., et al. Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study. Influenza and Other Respir. Viruses 12:2 (2018), 267–278.
48. Makau, J.N., Watanabe, K., Ishikawa, T., et al. Identification of small molecule inhibitors for influenza a virus using in silico and in vitro approaches. PLoS One, 12(3), 2017, e0173582.
49. Marathe, B.M., Wong, S.-S., Vogel, P., et al. Combinations of oseltamivir and T-705 extend the treatment window for highly pathogenic influenza A(H5N1) virus infection in mice. Sci. Rep., 6, 2016, 26742.
50. Massari, S., Nannetti, G., Desantis, J., et al. A broad anti-influenza hybrid small molecule that potently disrupts the interaction of polymerase acidic protein–basic protein 1 (PA-PB1) subunits. J. Med. Chem. 58:9 (2015), 3830–3842.
51. McKimm-Breschkin, J.L., “Influenza Neuraminidase Inhibitors: Antiviral Action and Mechanisms of resistance.” Influenza and Other Respiratory Viruses 7 Suppl 1(Suppl Suppl 1). 2013, 25–36.
52. McKimm-Breschkin, J.L., Jiang, S., Hui, D.S., et al. Prevention and treatment of respiratory viral infections: presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference. Antivir. Res. 149 (2018), 118–142.
53. Memoli, M.J., Hrabal, R.J., Hassantoufighi, A., et al. Rapid selection of oseltamivir- and peramivir-resistant pandemic H1N1 virus during therapy in 2 immunocompromised hosts. Clin. Infect. Dis.: Off. Publ. Infect. Dis. Soc. Am. 50:9 (2010), 1252–1255.
54. Ministry of Health, L. a. W., Report on the Deliberation Results., 2018 Retrieved 21/1/2019, 2019.
55. Ministry of Health, L. a. W., Revisions of Precautions Baloxavir Marboxil. 2019, PMDA.
56. Moscona, A., Neuraminidase inhibitors for influenza. N. Engl. J. Med. 353:13 (2005), 1363–1373.
57. Muratore, G., Goracci, L., Mercorelli, B., et al. Small molecule inhibitors of influenza A and B viruses that act by disrupting subunit interactions of the viral polymerase. Proc. Natl. Acad. Sci. Unit. States Am. 109:16 (2012), 6247–6252.
58. Muthuri, S.G., Venkatesan, S., Myles, P.R., et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. The Lancet Respir. Med. 2:5 (2014), 395–404.
59. National Institute of Infectious Diseases, Antiviral Resistance Surveillance in Japan (As of March 4 2019). 2019 Retrieved 12/03/2019, 2019.
60. Nguyen-Van-Tam, J.S., Venkatesan, S., Muthuri, S.G., et al. Neuraminidase inhibitors: who, when, where?. Clin. Microbiol. Infect. 21:3 (2015), 222–225.
61. Okoli, G.N., Otete, H.E., Beck, C.R., et al. Use of neuraminidase inhibitors for rapid containment of influenza: a systematic review and meta-analysis of individual and household transmission studies. PLoS One, 9(12), 2014, e113633.
62. Omoto, S., Speranzini, V., Hashimoto, T., et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci. Rep., 8(1), 2018, 9633.
63. Patel, T.S., Cinti, S., Sun, D., et al. Oseltamivir for pandemic influenza preparation: maximizing the use of an existing stockpile. Am. J. Infect. Contr. 45:3 (2017), 303–305.
64. Poon, L.L.M., Pritlove, D.C., Fodor, E., et al. Direct evidence that the poly(A) tail of influenza a virus mRNA is synthesized by reiterative copying of a U track in the virion RNA template. J. Virol. 73:4 (1999), 3473–3476.
65. Rocha-Pereira, J., Jochmans, D., Dallmeier, K., et al. Favipiravir (T-705) inhibits in vitro norovirus replication. Biochem. Biophys. Res. Commun. 424:4 (2012), 777–780.
66. Saito, R., Sato, I., Suzuki, Y., et al. Reduced effectiveness of oseltamivir in children infected with oseltamivir-resistant influenza a (H1N1) viruses with His275Tyr mutation. Pediatr. Infect. Dis. J. 29:10 (2010), 898–904.
67. Shionogi, XOFLUZATM (Baloxavir Marboxil) Tablets 10mg/20mg for the Treatment of Influenza Types A and B Launched in Japan. 2018 Retrieved March 14, 2018, from http://www.shionogi.co.jp/en/company/news/2018/pmrltj0000003oid-att/e180314.pdf.
68. Shobugawa, Y., Saito, R., Sato, I., et al. Recurrence and persistence of fever in children who developed amantadine-resistant influenza viruses after treatment. Tohoku J. Exp. Med. 214:2 (2008), 129–138.
69. Silvennoinen, H., Lehtinen, P., Heinonen, S., et al. Early oseltamivir treatment of influenza in children 1–3 Years of age: a randomized controlled trial. Clin. Infect. Dis. 51:8 (2010), 887–894.
70. Smither, S.J., Eastaugh, L.S., Steward, J.A., et al. Post-exposure efficacy of Oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model. Antivir. Res. 104 (2014), 153–155.
71. Stevaert, A., Naesens, L., The influenza virus polymerase complex: an update on its structure, functions, and significance for antiviral drug design. Med. Res. Rev. 36:6 (2016), 1127–1173.
72. Su, C.-Y., Cheng, T.-J.R., Lin, M.-I., et al. High-throughput identification of compounds targeting influenza RNA-dependent RNA polymerase activity. Proc. Natl. Acad. Sci. Unit. States Am. 107:45 (2010), 19151–19156.
73. Sugaya, N., Widespread use of neuraminidase inhibitors in Japan. J. Infect. Chemother. 17:5 (2011), 595–601.
74. Takashita, E., Ejima, M., Ogawa, R., et al. Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir. Antivir. Res. 132 (2016), 170–177.
75. Takashita, E., Kawakami, C., Morita, H., et al. Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018. Euro Surveill., 24(3), 2019, 1800698.
76. Takashita, E., Kawakami, C., Ogawa, R., et al. Influenza A(H3N2) virus exhibiting reduced susceptibility to baloxavir due to a polymerase acidic subunit I38T substitution detected from a hospitalised child without prior baloxavir treatment, Japan, January 2019. Euro Surveill., 24(12), 2019, 1900170.
77. Takashita, E., Meijer, A., Lackenby, A., et al. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2013–2014. Antivir. Res. 117 (2015), 27–38.
78. Toyama Chemical, AVIGAN Tablets. 2018.
79. Treanor, J.J., Hayden, F.G., Vrooman, P.S., et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. J. Am. Med. Assoc. 283:8 (2000), 1016–1024.
80. Trevejo, J.M., Asmal, M., Vingerhoets, J., et al. Pimodivir treatment in adult volunteers experimentally inoculated with live influenza virus: a Phase IIa, randomized, double-blind, placebo-controlled study. Antivir. Ther., 23, 2017.
81. Uehara, T., Hayden, F.G., Kawaguchi, K., et al. Treatment emergent influenza virus variants with reduced baloxavir susceptibility: impact on clinical and virologic outcomes in uncomplicated influenza. JID (J. Infect. Dis.), 2019 (submitted for publication).
82. Uehara, T., Shishido, T., Ishibashi, T., et al. Inhibitor of Cap‐dependent Endonuclease of Influenza A and B Virus, Leads to Rapid and Profound Viral Load Reduction. Options for the Control of Influenza. 2016 (Chicago, USA).
83. US Food and Drug Administration, FDA approves new drug to treat influenza. Retrieved October 24, 2018, from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624226.htm, 2018.
84. Uyeki, T.M., Bernstein, H.H., Bradley, J.S., et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. 2018.
85. Venkatesan, S., Myles, P.R., Leonardi-Bee, J., et al. Impact of outpatient neuraminidase inhibitor treatment in patients infected with influenza A(H1N1)pdm09 at high risk of hospitalization: an individual participant data metaanalysis. Clin. Infect. Dis. 64:10 (2017), 1328–1334.
86. Whitley, R., Hayden, F.G., Reisinger, K., et al. Oral oseltamivir treatment of influenza in children. Pediatr. Infect. Dis. J. 20:2 (2001), 127–133.
87. Whitley, R.J., Boucher, C.A., Lina, B., et al. Global assessment of resistance to neuraminidase inhibitors, 2008–2011: the influenza resistance information study (IRIS). Clin. Infect. Dis. 56:9 (2013), 1197–1205.
88. Witek, J., Overview of RSV and Influenza Programmes. International Society for Influenza and Other Respiratory Virus Diseases -Advances in Respiratory Viral Therapeutics. 2018 (Washington).
89. World Health Organisation, Standard Guidelines for the Clinical Management of Severe Influenza Virus Infections Initial Guideline Development Group (GDG) Meeting. 2018 Retrieved 11/2/2019, 2019.
90. Yogaratnam, J., Rito, J., Kakuda, T.N., et al. Antiviral activity, safety, and pharmacokinetics of AL-794, a novel oral influenza endonuclease inhibitor: results of an influenza human challenge study. J. Infect. Dis. 219:2 (2019), 177–185.
91. Zheng, B., Lau, C.C.Y., Tse, H., et al. Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin. Infect. Dis. 50:6 (2010), 850–859.