Susceptibility of paramyxoviruses and filoviruses to inhibition by 2′-monofluoro- and 2′-difluoro-4′-azidocytidine analogs

Antiviral Research

Volumn 153, Issue , 2018, Pages 101-113

  Lo, Michael K ^a   Jordan, Paul C ^b   Stevens, Sarah ^b   Tam, Yuen ^b   Deval, Jerome ^b   Nichol, Stuart T ^a   Spiropoulou, Christina F ^a  

^a CENTERS FOR DISEASE CONTROL AND PREVENTION   (United States)

^b a Janssen Pharmaceutical Company of Johnson Johnson Inc   (United States)

Author keywords

Antiviral; Ebola virus; Filovirus; Henipavirus; Nipah virus; Nucleoside analog; Paramyxovirus; R1479

Indexed keywords

2' DIFLUORO 4' AZIDOCYTIDINE DERIVATIVE; 2' MONOFLUORO 4' AZIDOCYTIDINE DERIVATIVE; 4' AZIDOCYTIDINE; ANTIVIRUS AGENT; CYTIDINE DERIVATIVE; NUCLEOSIDE DERIVATIVE; RNA DIRECTED RNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG; 4'-AZIDOCYTIDINE; CYTIDINE;

ANTIVIRAL ACTIVITY; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CELL VIABILITY; COMPARATIVE STUDY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG SYNTHESIS; EBOLAVIRUS; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; FEMALE; FILOVIRUS; HENDRA VIRUS; HUMAN; HUMAN CELL; MEASLES VIRUS; NEGATIVE-STRAND RNA VIRUS; NIPAH VIRUS; NONHUMAN; PARAMYXOVIRIDAE; PARAMYXOVIRINAE; PRIORITY JOURNAL; RAVN VIRUS; SUDAN VIRUS; ANALOGS AND DERIVATIVES; DRUG EFFECT; HENIPAVIRUS; MARBURGVIRUS; MICROBIAL SENSITIVITY TEST;

ANTIVIRAL AGENTS; CYTIDINE; EBOLAVIRUS; HENIPAVIRUS; MARBURGVIRUS; MICROBIAL SENSITIVITY TESTS;

EID: 85044737036     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2018.03.009     Document Type: Article

References (49)

1. Albarino, C.G., Wiggleton Guerrero, L., Lo, M.K., Nichol, S.T., Towner, J.S., Development of a reverse genetics system to generate a recombinant Ebola virus Makona expressing a green fluorescent protein. Virology 484 (2015), 259–264.
2. Arnold, J.J., Sharma, S.D., Feng, J.Y., Ray, A.S., Smidansky, E.D., Kireeva, M.L., Cho, A., Perry, J., Vela, J.E., Park, Y., Xu, Y., Tian, Y., Babusis, D., Barauskus, O., Peterson, B.R., Gnatt, A., Kashlev, M., Zhong, W., Cameron, C.E., Sensitivity of mitochondrial transcription and resistance of RNA polymerase II dependent nuclear transcription to antiviral ribonucleosides. PLoS Pathog., 8, 2012, e1003030.
3. Baranovich, T., Wong, S.S., Armstrong, J., Marjuki, H., Webby, R.J., Webster, R.G., Govorkova, E.A., T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J. Virol. 87 (2013), 3741–3751.
4. Bird, B.H., Albarino, C.G., Nichol, S.T., Rift Valley fever virus lacking NSm proteins retains high virulence in vivo and may provide a model of human delayed onset neurologic disease. Virology 362 (2007), 10–15.
5. Broder, C.C., Weir, D.L., Reid, P.A., Hendra virus and Nipah virus animal vaccines. Vaccine 34 (2016), 3525–3534.
6. CDC, Outbreaks Chronology: Ebola Virus Disease. 2017.
7. Chen, P., Liu, Z., Liu, S., Xie, Z., Aimiuwu, J., Pang, J., Klisovic, R., Blum, W., Grever, M.R., Marcucci, G., Chan, K.K., A LC-MS/MS method for the analysis of intracellular nucleoside triphosphate levels. Pharm. Res. 26 (2009), 1504–1515.
8. Chen, Y.L., Abdul Ghafar, N., Karuna, R., Fu, Y., Lim, S.P., Schul, W., Gu, F., Herve, M., Yokohama, F., Wang, G., Cerny, D., Fink, K., Blasco, F., Shi, P.Y., Activation of peripheral blood mononuclear cells by dengue virus infection depotentiates balapiravir. J. Virol. 88 (2014), 1740–1747.
9. Clarke, M.O., Mackman, R., Byun, D., Hui, H., Barauskas, O., Birkus, G., Chun, B.K., Doerffler, E., Feng, J., Karki, K., Lee, G., Perron, M., Siegel, D., Swaminathan, S., Lee, W., Discovery of beta-D-2’-deoxy-2’-alpha-fluoro-4’-alpha-cyano-5-aza-7,9-dideaza adenosine as a potent nucleoside inhibitor of respiratory syncytial virus with excellent selectivity over mitochondrial RNA and DNA polymerases. Bioorg Med. Chem. Lett. 25 (2015), 2484–2487.
10. Deval, J., Hong, J., Wang, G., Taylor, J., Smith, L.K., Fung, A., Stevens, S.K., Liu, H., Jin, Z., Dyatkina, N., Prhavc, M., Stoycheva, A.D., Serebryany, V., Liu, J., Smith, D.B., Tam, Y., Zhang, Q., Moore, M.L., Fearns, R., Chanda, S.M., Blatt, L.M., Symons, J.A., Beigelman, L., Molecular basis for the selective inhibition of respiratory syncytial virus RNA polymerase by 2’-fluoro-4’-chloromethyl-cytidine triphosphate. PLoS Pathog., 11, 2015, e1004995.
11. Escaffre, O., Borisevich, V., Carmical, J.R., Prusak, D., Prescott, J., Feldmann, H., Rockx, B., Henipavirus pathogenesis in human respiratory epithelial cells. J. Virol. 87 (2013), 3284–3294.
12. Eyer, L., Smidkova, M., Nencka, R., Neca, J., Kastl, T., Palus, M., De Clercq, E., Ruzek, D., Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus. Antivir. Res. 133 (2016), 119–129.
13. Geisbert, T.W., Mire, C.E., Geisbert, J.B., Chan, Y.P., Agans, K.N., Feldmann, F., Fenton, K.A., Zhu, Z., Dimitrov, D.S., Scott, D.P., Bossart, K.N., Feldmann, H., Broder, C.C., Therapeutic treatment of Nipah virus infection in nonhuman primates with a neutralizing human monoclonal antibody. Sci. Transl. Med., 6, 2014 242ra282.
14. Hallak, L.K., Spillmann, D., Collins, P.L., Peeples, M.E., Glycosaminoglycan sulfation requirements for respiratory syncytial virus infection. J. Virol. 74 (2000), 10508–10513.
15. Hotard, A.L., He, B., Nichol, S.T., Spiropoulou, C.F., Lo, M.K., 4’-Azidocytidine (R1479) inhibits henipaviruses and other paramyxoviruses with high potency. Antivir. Res. 144 (2017), 147–152.
16. Johnson, E.D., Johnson, B.K., Silverstein, D., Tukei, P., Geisbert, T.W., Sanchez, A.N., Jahrling, P.B., Characterization of a new Marburg virus isolated from a 1987 fatal case in Kenya. Arch. Virol. Suppl. 11 (1996), 101–114.
17. Jordan, P.C., Liu, C., Raynaud, P., Lo, M.K., Spiropoulou, C.F., Symons, J.A., Beigelman, L., Deval, J., Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase. PLOS Pathog., 14, 2018, e1006889.
18. Klumpp, K., Kalayanov, G., Ma, H., Le Pogam, S., Leveque, V., Jiang, W.R., Inocencio, N., De Witte, A., Rajyaguru, S., Tai, E., Chanda, S., Irwin, M.R., Sund, C., Winqist, A., Maltseva, T., Eriksson, S., Usova, E., Smith, M., Alker, A., Najera, I., Cammack, N., Martin, J.A., Johansson, N.G., Smith, D.B., 2’-deoxy-4’-azido nucleoside analogs are highly potent inhibitors of hepatitis C virus replication despite the lack of 2’-alpha-hydroxyl groups. J. Biol. Chem. 283 (2008), 2167–2175.
19. Klumpp, K., Leveque, V., Le Pogam, S., Ma, H., Jiang, W.R., Kang, H., Granycome, C., Singer, M., Laxton, C., Hang, J.Q., Sarma, K., Smith, D.B., Heindl, D., Hobbs, C.J., Merrett, J.H., Symons, J., Cammack, N., Martin, J.A., Devos, R., Najera, I., The novel nucleoside analog R1479 (4’-azidocytidine) is a potent inhibitor of NS5B-dependent RNA synthesis and hepatitis C virus replication in cell culture. J. Biol. Chem. 281 (2006), 3793–3799.
20. Kobinger, G.P., Weiner, D.J., Yu, Q.C., Wilson, J.M., Filovirus-pseudotyped lentiviral vector can efficiently and stably transduce airway epithelia in vivo. Nat. Biotechnol. 19 (2001), 225–230.
21. Lamunu, M., Lutwama, J.J., Kamugisha, J., Opio, A., Nambooze, J., Ndayimirije, N., Okware, S., Containing a haemorrhagic fever epidemic: the Ebola experience in Uganda (October 2000-January 2001). Int. J. Infect. Dis. 8 (2004), 27–37.
22. Lo, M.K., Jordan, R., Arvey, A., Sudhamsu, J., Shrivastava-Ranjan, P., Hotard, A.L., Flint, M., McMullan, L.K., Siegel, D., Clarke, M.O., Mackman, R.L., Hui, H.C., Perron, M., Ray, A.S., Cihlar, T., Nichol, S.T., Spiropoulou, C.F., GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses. Sci. Rep., 7, 2017, 43395.
23. Lo, M.K., Nichol, S.T., Spiropoulou, C.F., Evaluation of luciferase and GFP-expressing Nipah viruses for rapid quantitative antiviral screening. Antivir. Res. 106 (2014), 53–60.
24. Luby, S.P., Gurley, E.S., Epidemiology of henipavirus disease in humans. Curr. Top. Microbiol. Immunol. 359 (2012), 25–40.
25. Madrid, P.B., Panchal, R.G., Warren, T.K., Shurtleff, A.C., Endsley, A.N., Green, C.E., Kolokoltsov, A., Davey, R., Manger, I.D., Gilfillan, L., Bavari, S., Tanga, M.J., Evaluation of Ebola virus inhibitors for drug repurposing. ACS Infect. Dis. 1 (2015), 317–326.
26. Mendoza, E.J., Racine, T., Kobinger, G.P., The ongoing evolution of antibody-based treatments for Ebola virus infection. Immunotherapy 9 (2017), 435–450.
27. Mire, C.E., Geisbert, T.W., Feldmann, H., Marzi, A., Ebola virus vaccines - reality or fiction?. Expert Rev. Vaccines 15 (2016), 1421–1430.
28. Nelson, D.R., Zeuzem, S., Andreone, P., Ferenci, P., Herring, R., Jensen, D.M., Marcellin, P., Pockros, P.J., Rodriguez-Torres, M., Rossaro, L., Rustgi, V.K., Sepe, T., Sulkowski, M., Thomason, I.R., Yoshida, E.M., Chan, A., Hill, G., Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients. Ann. Hepatol. 11 (2012), 15–31.
29. Nguyen, N.M., Tran, C.N., Phung, L.K., Duong, K.T., Huynh Hle, A., Farrar, J., Nguyen, Q.T., Tran, H.T., Nguyen, C.V., Merson, L., Hoang, L.T., Hibberd, M.L., Aw, P.P., Wilm, A., Nagarajan, N., Nguyen, D.T., Pham, M.P., Nguyen, T.T., Javanbakht, H., Klumpp, K., Hammond, J., Petric, R., Wolbers, M., Nguyen, C.T., Simmons, C.P., A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. J. Infect. Dis. 207 (2013), 1442–1450.
30. Noton, S.L., Deflube, L.R., Tremaglio, C.Z., Fearns, R., The respiratory syncytial virus polymerase has multiple RNA synthesis activities at the promoter. PLoS Pathog., 8, 2012, e1002980.
31. Oestereich, L., Ludtke, A., Wurr, S., Rieger, T., Munoz-Fontela, C., Gunther, S., Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antivir. Res. 105 (2014), 17–21.
32. Qiu, X., Wong, G., Audet, J., Bello, A., Fernando, L., Alimonti, J.B., Fausther-Bovendo, H., Wei, H., Aviles, J., Hiatt, E., Johnson, A., Morton, J., Swope, K., Bohorov, O., Bohorova, N., Goodman, C., Kim, D., Pauly, M.H., Velasco, J., Pettitt, J., Olinger, G.G., Whaley, K., Xu, B., Strong, J.E., Zeitlin, L., Kobinger, G.P., Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 514 (2014), 47–53.
33. Ray, A.S., Hitchcock, M.J.M., Metabolism of antiviral nucleosides and nucleotides. Lafemina, R.L., (eds.) Antiviral Research: Strategies in Antiviral Drug Discovery, 2009, ASM Press, Washington, DC.
34. Reed, L.J., Muench, H., A simple method of estimating fifty percent endpoints. Am. J. Hyg. 27 (1938), 493–497.
35. Rennick, L.J., de Vries, R.D., Carsillo, T.J., Lemon, K., van Amerongen, G., Ludlow, M., Nguyen, D.T., Yuksel, S., Verburgh, R.J., Haddock, P., McQuaid, S., Duprex, W.P., de Swart, R.L., Live-attenuated measles virus vaccine targets dendritic cells and macrophages in muscle of nonhuman primates. J. Virol. 89 (2015), 2192–2200.
36. Sanchez, A., Rollin, P.E., Complete genome sequence of an Ebola virus (Sudan species) responsible for a 2000 outbreak of human disease in Uganda. Virus Res. 113 (2005), 16–25.
37. Sheahan, T.P., Sims, A.C., Graham, R.L., Menachery, V.D., Gralinski, L.E., Case, J.B., Leist, S.R., Pyrc, K., Feng, J.Y., Trantcheva, I., Bannister, R., Park, Y., Babusis, D., Clarke, M.O., Mackman, R.L., Spahn, J.E., Palmiotti, C.A., Siegel, D., Ray, A.S., Cihlar, T., Jordan, R., Denison, M.R., Baric, R.S., Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci. Transl. Med., 9, 2017.
38. Smith, D.B., Kalayanov, G., Sund, C., Winqvist, A., Maltseva, T., Leveque, V.J., Rajyaguru, S., Le Pogam, S., Najera, I., Benkestock, K., Zhou, X.X., Kaiser, A.C., Maag, H., Cammack, N., Martin, J.A., Swallow, S., Johansson, N.G., Klumpp, K., Smith, M., The design, synthesis, and antiviral activity of monofluoro and difluoro analogues of 4’-azidocytidine against hepatitis C virus replication: the discovery of 4’-azido-2’-deoxy-2’-fluorocytidine and 4’-azido-2’-dideoxy-2’,2’-difluorocytidine. J. Med. Chem. 52 (2009), 2971–2978.
39. Smith, D.B., Martin, J.A., Klumpp, K., Baker, S.J., Blomgren, P.A., Devos, R., Granycome, C., Hang, J., Hobbs, C.J., Jiang, W.R., Laxton, C., Le Pogam, S., Leveque, V., Ma, H., Maile, G., Merrett, J.H., Pichota, A., Sarma, K., Smith, M., Swallow, S., Symons, J., Vesey, D., Najera, I., Cammack, N., Design, synthesis, and antiviral properties of 4’-substituted ribonucleosides as inhibitors of hepatitis C virus replication: the discovery of R1479. Bioorg Med. Chem. Lett. 17 (2007), 2570–2576.
40. Taylor, R., Kotian, P., Warren, T., Panchal, R., Bavari, S., Julander, J., Dobo, S., Rose, A., El-Kattan, Y., Taubenheim, B., Babu, Y., Sheridan, W.P., BCX4430-A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease. J. Infect. Public Health 9 (2016), 220–226.
41. Towner, J.S., Khristova, M.L., Sealy, T.K., Vincent, M.J., Erickson, B.R., Bawiec, D.A., Hartman, A.L., Comer, J.A., Zaki, S.R., Stroher, U., Gomes da Silva, F., del Castillo, F., Rollin, P.E., Ksiazek, T.G., Nichol, S.T., Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. J. Virol. 80 (2006), 6497–6516.
42. Towner, J.S., Paragas, J., Dover, J.E., Gupta, M., Goldsmith, C.S., Huggins, J.W., Nichol, S.T., Generation of eGFP expressing recombinant Zaire ebolavirus for analysis of early pathogenesis events and high-throughput antiviral drug screening. Virology 332 (2005), 20–27.
43. Van Rompay, A.R., Norda, A., Linden, K., Johansson, M., Karlsson, A., Phosphorylation of uridine and cytidine nucleoside analogs by two human uridine-cytidine kinases. Mol. Pharmacol. 59 (2001), 1181–1186.
44. Veljkovic, V., Loiseau, P.M., Figadere, B., Glisic, S., Veljkovic, N., Perovic, V.R., Cavanaugh, D.P., Branch, D.R., Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection. F1000Res, 4, 2015, 34.
45. Wang, G., Deval, J., Hong, J., Dyatkina, N., Prhavc, M., Taylor, J., Fung, A., Jin, Z., Stevens, S.K., Serebryany, V., Liu, J., Zhang, Q., Tam, Y., Chanda, S.M., Smith, D.B., Symons, J.A., Blatt, L.M., Beigelman, L., 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. 58 (2015), 1862–1878.
46. Warren, T.K., Jordan, R., Lo, M.K., Ray, A.S., Mackman, R.L., Soloveva, V., Siegel, D., Perron, M., Bannister, R., Hui, H.C., Larson, N., Strickley, R., Wells, J., Stuthman, K.S., Van Tongeren, S.A., Garza, N.L., Donnelly, G., Shurtleff, A.C., Retterer, C.J., Gharaibeh, D., Zamani, R., Kenny, T., Eaton, B.P., Grimes, E., Welch, L.S., Gomba, L., Wilhelmsen, C.L., Nichols, D.K., Nuss, J.E., Nagle, E.R., Kugelman, J.R., Palacios, G., Doerffler, E., Neville, S., Carra, E., Clarke, M.O., Zhang, L., Lew, W., Ross, B., Wang, Q., Chun, K., Wolfe, L., Babusis, D., Park, Y., Stray, K.M., Trancheva, I., Feng, J.Y., Barauskas, O., Xu, Y., Wong, P., Braun, M.R., Flint, M., McMullan, L.K., Chen, S.S., Fearns, R., Swaminathan, S., Mayers, D.L., Spiropoulou, C.F., Lee, W.A., Nichol, S.T., Cihlar, T., Bavari, S., Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 531 (2016), 381–385.
47. Warren, T.K., Wells, J., Panchal, R.G., Stuthman, K.S., Garza, N.L., Van Tongeren, S.A., Dong, L., Retterer, C.J., Eaton, B.P., Pegoraro, G., Honnold, S., Bantia, S., Kotian, P., Chen, X., Taubenheim, B.R., Welch, L.S., Minning, D.M., Babu, Y.S., Sheridan, W.P., Bavari, S., Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature 508 (2014), 402–405.
48. Welch, S.R., Guerrero, L.W., Chakrabarti, A.K., McMullan, L.K., Flint, M., Bluemling, G.R., Painter, G.R., Nichol, S.T., Spiropoulou, C.F., Albarino, C.G., Lassa and Ebola virus inhibitors identified using minigenome and recombinant virus reporter systems. Antivir. Res. 136 (2016), 9–18.
49. Zhang, L., Bukreyev, A., Thompson, C.I., Watson, B., Peeples, M.E., Collins, P.L., Pickles, R.J., Infection of ciliated cells by human parainfluenza virus type 3 in an in vitro model of human airway epithelium. J. Virol. 79 (2005), 1113–1124.