Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase

Antiviral Research

Volumn 169, Issue , 2019, Pages

  Brown, Ariane J ^a   Won, John J ^a   Graham, Rachel L ^a   Dinnon, Kenneth H ^a   Sims, Amy C ^a   Feng, Joy Y ^b   Cihlar, Tomas ^b   Denison, Mark R ^c   Baric, Ralph S ^a   Sheahan, Timothy P ^a  

^a IL   (United States)

^b GILEAD SCIENCES   (United States)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Broad spectrum antivirals; Coronavirus; Emerging viruses; GS 5743; Remdesivir

Indexed keywords

GENOMIC RNA; REMDESIVIR; RNA DIRECTED RNA POLYMERASE; ADENOSINE PHOSPHATE; ALANINE; ANTIVIRUS AGENT;

ANTIVIRAL ACTIVITY; ARTICLE; CORONAVIRINAE; CYTOTOXICITY; DELTACORONAVIRUS; EC50; FLUORESCENCE IN SITU HYBRIDIZATION; GENETIC VARIABILITY; HUMAN; HUMAN CELL; HUMAN CORONAVIRUS OC43; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; NONHUMAN; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SARS CORONAVIRUS; ANIMAL; BETACORONAVIRUS; CELL LINE; CLASSIFICATION; CORONAVIRUS INFECTION; DRUG EFFECT; GENETICS; PHYLOGENY; PIG; VIROLOGY; VIRUS REPLICATION;

ADENOSINE MONOPHOSPHATE; ALANINE; ANIMALS; ANTIVIRAL AGENTS; BETACORONAVIRUS; CELL LINE; CORONAVIRUS; CORONAVIRUS INFECTIONS; HUMANS; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; PHYLOGENY; RNA REPLICASE; SARS VIRUS; SWINE; VIRUS REPLICATION;

EID: 85067639261     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2019.104541     Document Type: Article

References (42)

1. Agostini, M.L., Andres, E.L., Sims, A.C., Graham, R.L., Sheahan, T.P., Lu, X., Smith, E.C., Case, J.B., Feng, J.Y., Jordan, R., Ray, A.S., Cihlar, T., Siegel, D., Mackman, R.L., Clarke, M.O., Baric, R.S., Denison, M.R., Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio, 9, 2018.
2. Barnard, D.L., Day, C.W., Bailey, K., Heiner, M., Montgomery, R., Lauridsen, L., Chan, P.K., Sidwell, R.W., Evaluation of immunomodulators, interferons and known in vitro SARS-coV inhibitors for inhibition of SARS-coV replication in BALB/c mice. Antivir. Chem. Chemother. 17 (2006), 275–284.
3. Beall, A., Yount, B., Lin, C.M., Hou, Y., Wang, Q., Saif, L., Baric, R., Characterization of a pathogenic full-length cDNA Clone and transmission model for porcine epidemic diarrhea virus strain PC22A. mBio, 7, 2016, e01451-01415.
4. Carman, K.B., Calik, M., Karal, Y., Isikay, S., Kocak, O., Ozcelik, A., Yazar, A.S., Nuhoglu, C., Sag, C., Kilic, O., Dinleyici, M., Lacinel Gurlevik, S., Yimenicioglu, S., Ekici, A., Perk, P., Tosun, A., Isik, I., Yarar, C., Arslantas, D., Dinleyici, E.C., E.S.G, Viral etiological causes of febrile seizures for respiratory pathogens (EFES Study). Hum. Vaccines Immunother., 2018, 1–7.
5. Chan, J.F., Chan, K.H., Kao, R.Y., To, K.K., Zheng, B.J., Li, C.P., Li, P.T., Dai, J., Mok, F.K., Chen, H., Hayden, F.G., Yuen, K.Y., Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J. Infect. 67 (2013), 606–616.
6. de Wilde, A.H., Jochmans, D., Posthuma, C.C., Zevenhoven-Dobbe, J.C., van Nieuwkoop, S., Bestebroer, T.M., van den Hoogen, B.G., Neyts, J., Snijder, E.J., Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob. Agents Chemother. 58 (2014), 4875–4884.
7. de Wit, E., van Doremalen, N., Falzarano, D., Munster, V.J., SARS and MERS: recent insights into emerging coronaviruses. Nat. Rev. Microbiol. 14 (2016), 523–534.
8. Dijkman, R., Jebbink, M.F., Gaunt, E., Rossen, J.W., Templeton, K.E., Kuijpers, T.W., van der Hoek, L., The dominance of human coronavirus OC43 and NL63 infections in infants. J. Clin. Virol. 53 (2012), 135–139.
9. Falsey, A.R., Walsh, E.E., Hayden, F.G., Rhinovirus and coronavirus infection-associated hospitalizations among older adults. J. Infect. Dis. 185 (2002), 1338–1341.
10. Heimdal, I., Moe, N., Krokstad, S., Christensen, A., Skanke, L.H., Nordbo, S.A., Dollner, H., Human coronavirus in hospitalized children with respiratory tract infections: a nine-year-long, population-based study from Norway. J. Infect. Dis. 219:8 (2019 Apr 8), 1198–1206, 10.1093/infdis/jiy646.
11. Hu, B., Ge, X., Wang, L.F., Shi, Z., Bat origin of human coronaviruses. Virol. J., 12, 2015, 221.
12. Hu, H., Jung, K., Vlasova, A.N., Chepngeno, J., Lu, Z., Wang, Q., Saif, L.J., Isolation and characterization of porcine deltacoronavirus from pigs with diarrhea in the United States. J. Clin. Microbiol. 53 (2015), 1537–1548.
13. Huang, Y.W., Dickerman, A.W., Pineyro, P., Li, L., Fang, L., Kiehne, R., Opriessnig, T., Meng, X.J., Origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus strains in the United States. mBio, 4, 2013 e00737-00713.
14. Huynh, J., Li, S., Yount, B., Smith, A., Sturges, L., Olsen, J.C., Nagel, J., Johnson, J.B., Agnihothram, S., Gates, J.E., Frieman, M.B., Baric, R.S., Donaldson, E.F., Evidence supporting a zoonotic origin of human coronavirus strain NL63. J. Virol. 86 (2012), 12816–12825.
15. Ibarra, K.D., Pfeiffer, J.K., Reduced ribavirin antiviral efficacy via nucleoside transporter-mediated drug resistance. J. Virol. 83 (2009), 4538–4547.
16. 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.
17. Jung, K., Hu, H., Eyerly, B., Lu, Z., Chepngeno, J., Saif, L.J., Pathogenicity of 2 porcine deltacoronavirus strains in gnotobiotic pigs. Emerg. Infect. Dis. 21 (2015), 650–654.
18. Kirchdoerfer, R.N., Ward, A.B., Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat. Commun., 10, 2019, 2342.
19. Lassnig, C., Sanchez, C.M., Egerbacher, M., Walter, I., Majer, S., Kolbe, T., Pallares, P., Enjuanes, L., Muller, M., Development of a transgenic mouse model susceptible to human coronavirus 229E. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 8275–8280.
20. Lau, S.K., Poon, R.W., Wong, B.H., Wang, M., Huang, Y., Xu, H., Guo, R., Li, K.S., Gao, K., Chan, K.H., Zheng, B.J., Woo, P.C., Yuen, K.Y., Coexistence of different genotypes in the same bat and serological characterization of Rousettus bat coronavirus HKU9 belonging to a novel Betacoronavirus subgroup. J. Virol. 84 (2010), 11385–11394.
21. Leung, S., Bendayan, R., Uptake properties of lamivudine (3TC) by a continuous renal epithelial cell line. Can. J. Physiol. Pharmacol. 79 (2001), 59–66.
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. Loens, K., van Loon, A.M., Coenjaerts, F., van Aarle, Y., Goossens, H., Wallace, P., Claas, E.J., Ieven, M., Group, G.S., Performance of different mono- and multiplex nucleic acid amplification tests on a multipathogen external quality assessment panel. J. Clin. Microbiol. 50 (2012), 977–987.
24. Matsuda, M., Tsurusaki, S., Miyata, N., Saijou, E., Okochi, H., Miyajima, A., Tanaka, M., Oncostatin M causes liver fibrosis by regulating cooperation between hepatic stellate cells and macrophages in mice. Hepatology 67 (2018), 296–312.
25. Menachery, V.D., Yount, B.L. Jr., Sims, A.C., Debbink, K., Agnihothram, S.S., Gralinski, L.E., Graham, R.L., Scobey, T., Plante, J.A., Royal, S.R., Swanstrom, J., Sheahan, T.P., Pickles, R.J., Corti, D., Randell, S.H., Lanzavecchia, A., Marasco, W.A., Baric, R.S., SARS-like WIV1-CoV poised for human emergence. Proc. Natl. Acad. Sci. U. S. A. 113:11 (2016 Mar 15), 3048–3053, 10.1073/pnas.1517719113 Epub 2016 Mar 14.
26. Murphy, B.G., Perron, M., Murakami, E., Bauer, K., Park, Y., Eckstrand, C., Liepnieks, M., Pedersen, N.C., The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies. Vet. Microbiol. 219 (2018), 226–233.
27. Neuman, B.W., Joseph, J.S., Saikatendu, K.S., Serrano, P., Chatterjee, A., Johnson, M.A., Liao, L., Klaus, J.P., Yates, J.R. 3rd, Wuthrich, K., Stevens, R.C., Buchmeier, M.J., Kuhn, P., Proteomics analysis unravels the functional repertoire of coronavirus nonstructural protein 3. J. Virol. 82 (2008), 5279–5294.
28. Patrick, D.M., Petric, M., Skowronski, D.M., Guasparini, R., Booth, T.F., Krajden, M., McGeer, P., Bastien, N., Gustafson, L., Dubord, J., Macdonald, D., David, S.T., Srour, L.F., Parker, R., Andonov, A., Isaac-Renton, J., Loewen, N., McNabb, G., McNabb, A., Goh, S.H., Henwick, S., Astell, C., Guo, J.P., Drebot, M., Tellier, R., Plummer, F., Brunham, R.C., An outbreak of human coronavirus OC43 infection and serological cross-reactivity with SARS coronavirus. Can. J. Infect Dis. Med. Microbiol. 17 (2006), 330–336.
29. 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.
30. Shen, L., Yang, Y., Ye, F., Liu, G., Desforges, M., Talbot, P.J., Tan, W., Safe and sensitive antiviral screening platform based on recombinant human coronavirus OC43 expressing the luciferase reporter gene. Antimicrob. Agents Chemother. 60 (2016), 5492–5503.
31. Siegel, D., Hui, H.C., Doerffler, E., Clarke, M.O., Chun, K., Zhang, L., Neville, S., Carra, E., Lew, W., Ross, B., Wang, Q., Wolfe, L., Jordan, R., Soloveva, V., Knox, J., Perry, J., Perron, M., Stray, K.M., Barauskas, O., Feng, J.Y., Xu, Y., Lee, G., Rheingold, A.L., Ray, A.S., Bannister, R., Strickley, R., Swaminathan, S., Lee, W.A., Bavari, S., Cihlar, T., Lo, M.K., Warren, T.K., Mackman, R.L., Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine C-nucleoside (GS-5734) for the treatment of Ebola and emerging viruses. J. Med. Chem. 60 (2017), 1648–1661.
32. St-Jean, J.R., Jacomy, H., Desforges, M., Vabret, A., Freymuth, F., Talbot, P.J., Human respiratory coronavirus OC43: genetic stability and neuroinvasion. J. Virol. 78 (2004), 8824–8834.
33. Tchesnokov, E.P., Feng, J.Y., Porter, D.P., Gotte, M., Mechanism of inhibition of Ebola virus RNA-dependent RNA polymerase by remdesivir. Viruses, 11, 2019.
34. Tchesnokov, E.P., Raeisimakiani, P., Ngure, M., Marchant, D., Gotte, M., Recombinant RNA-dependent RNA polymerase complex of Ebola virus. Sci. Rep., 8, 2018, 3970.
35. Varghese, L., Zachariah, P., Vargas, C., LaRussa, P., Demmer, R.T., Furuya, Y.E., Whittier, S., Reed, C., Stockwell, M.S., Saiman, L., Epidemiology and clinical features of human coronaviruses in the pediatric population. J. Pediatr. Infect. Dis. Soc. 7 (2018), 151–158.
36. Vassilara, F., Spyridaki, A., Pothitos, G., Deliveliotou, A., Papadopoulos, A., A rare case of human coronavirus 229E associated with acute respiratory distress syndrome in a healthy adult. Case Rep. Infect. Dis., 2018, 2018, 6796839.
37. Vijgen, L., Keyaerts, E., Moes, E., Thoelen, I., Wollants, E., Lemey, P., Vandamme, A.M., Van Ranst, M., Complete genomic sequence of human coronavirus OC43: molecular clock analysis suggests a relatively recent zoonotic coronavirus transmission event. J. Virol. 79 (2005), 1595–1604.
38. Walsh, E.E., Shin, J.H., Falsey, A.R., Clinical impact of human coronaviruses 229E and OC43 infection in diverse adult populations. J. Infect. Dis. 208 (2013), 1634–1642.
39. 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.
40. Xu, X., Liu, Y., Weiss, S., Arnold, E., Sarafianos, S.G., Ding, J., Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design. Nucleic Acids Res. 31 (2003), 7117–7130.
41. Zhou, P., Fan, H., Lan, T., Yang, X.L., Shi, W.F., Zhang, W., Zhu, Y., Zhang, Y.W., Xie, Q.M., Mani, S., Zheng, X.S., Li, B., Li, J.M., Guo, H., Pei, G.Q., An, X.P., Chen, J.W., Zhou, L., Mai, K.J., Wu, Z.X., Li, D., Anderson, D.E., Zhang, L.B., Li, S.Y., Mi, Z.Q., He, T.T., Cong, F., Guo, P.J., Huang, R., Luo, Y., Liu, X.L., Chen, J., Huang, Y., Sun, Q., Zhang, X.L., Wang, Y.Y., Xing, S.Z., Chen, Y.S., Sun, Y., Li, J., Daszak, P., Wang, L.F., Shi, Z.L., Tong, Y.G., Ma, J.Y., Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature 556 (2018), 255–258.
42. Zumla, A., Chan, J.F., Azhar, E.I., Hui, D.S., Yuen, K.Y., Coronaviruses - drug discovery and therapeutic options. Nat. Rev. Drug Discov. 15 (2016), 327–347.