Rigid amphipathic fusion inhibitors demonstrate antiviral activity against African swine fever virus Free

Abstract

Rigid amphipathic fusion inhibitors (RAFIs) are a family of nucleoside derivatives that inhibit the infectivity of several enveloped viruses by interacting with virion envelope lipids and inhibiting fusion between viral and cellular membranes. Here we tested the antiviral activity of two RAFIs, 5-(Perylen-3-ylethynyl)-arabino-uridine (aUY11) and 5-(Perylen-3-ylethynyl)uracil-1-acetic acid (cm1UY11) against African swine fever virus (ASFV), for which no effective vaccine is available. Both compounds displayed a potent, dose-dependent inhibitory effect on ASFV infection in Vero cells. The major antiviral effect was observed when aUY11 and cm1UY11 were added at early stages of infection and maintained during the complete viral cycle. Furthermore, virucidal assay revealed a significant extracellular anti-ASFV activity for both compounds. We also found decrease in the synthesis of early and late viral proteins in Vero cells treated with cm1UY11. Finally, the inhibitory effect of aUY11 and cm1UY11 on ASFV infection in porcine alveolar macrophages was confirmed. Overall, our study has identified novel anti-ASFV compounds with potential for future therapeutic developments.

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2018-01-01
2024-03-28
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References

  1. Tulman ER, Delhon GA, Ku BK, Rock DL. African swine fever virus. Curr Top Microbiol Immunol 2009; 328:43–87[PubMed]
    [Google Scholar]
  2. Blome S, Gabriel C, Beer M. Pathogenesis of African swine fever in domestic pigs and European wild boar. Virus Res 2013; 173:122–130 [View Article][PubMed]
    [Google Scholar]
  3. Karalyan Z, Zakaryan H, Arzumanyan H, Sargsyan K, Voskanyan H et al. Pathology of porcine peripheral white blood cells during infection with African swine fever virus. BMC Vet Res 2012; 8:18 [View Article][PubMed]
    [Google Scholar]
  4. Zakaryan H, Karalova E, Voskanyan H, Ter-Pogossyan Z, Nersisyan N et al. Evaluation of hemostaseological status of pigs experimentally infected with African swine fever virus. Vet Microbiol 2014; 174:223–228 [View Article][PubMed]
    [Google Scholar]
  5. Cisek AA, Dąbrowska I, Gregorczyk KP, Wyżewski Z. African Swine Fever Virus: a new old enemy of Europe. Ann Parasitol 2016; 62:161–167[PubMed]
    [Google Scholar]
  6. Zakaryan H, Revilla Y. African swine fever virus: current state and future perspectives in vaccine and antiviral research. Vet Microbiol 2016; 185:15–19 [View Article][PubMed]
    [Google Scholar]
  7. Rock DL. Challenges for African swine fever vaccine development–"… perhaps the end of the beginning". Vet Microbiol 2017; 206:52–58 [View Article][PubMed]
    [Google Scholar]
  8. Carrasco L, Gómez-Villamandos JC, Bautista MJ, Martín de Las Mulas J, Villeda CJ et al. In vivo replication of African swine fever virus (Malawi '83) in neutrophils. Vet Res 1996; 27:55–62[PubMed]
    [Google Scholar]
  9. Pérez J, Bautista MJ, Rodríguez F, Wilkinson PJ, Sierra MA et al. Double-labelling immunohistochemical study of megakaryocytes in African swine fever. Vet Rec 1997; 141:386–390 [View Article][PubMed]
    [Google Scholar]
  10. Sánchez EG, Quintas A, Pérez-Núñez D, Nogal M, Barroso S et al. African swine fever virus uses macropinocytosis to enter host cells. PLoS Pathog 2012; 8:e1002754 [View Article][PubMed]
    [Google Scholar]
  11. Galindo I, Cuesta-Geijo MA, Hlavova K, Muñoz-Moreno R, Barrado-Gil L et al. African swine fever virus infects macrophages, the natural host cells, via clathrin- and cholesterol-dependent endocytosis. Virus Res 2015; 200:45–55 [View Article][PubMed]
    [Google Scholar]
  12. Hernáez B, Guerra M, Salas ML, Andrés G. African swine fever virus undergoes outer envelope disruption, capsid disassembly and inner envelope fusion before core release from multivesicular endosomes. PLoS Pathog 2016; 12:e1005595 [View Article][PubMed]
    [Google Scholar]
  13. Cuesta-Geijo MA, Chiappi M, Galindo I, Barrado-Gil L, Muñoz-Moreno R et al. Cholesterol flux is required for endosomal progression of African swine fever virus. J Virol 2015; 90:1534–1543 [Crossref]
    [Google Scholar]
  14. Dixon LK, Chapman DA, Netherton CL, Upton C. African swine fever virus replication and genomics. Virus Res 2013; 173:3–14 [View Article][PubMed]
    [Google Scholar]
  15. Salas ML, Andrés G. African swine fever virus morphogenesis. Virus Res 2013; 173:29–41 [View Article][PubMed]
    [Google Scholar]
  16. St Vincent MR, Colpitts CC, Ustinov AV, Muqadas M, Joyce MA et al. Rigid amphipathic fusion inhibitors, small molecule antiviral compounds against enveloped viruses. Proc Natl Acad Sci USA 2010; 107:17339–17344 [View Article][PubMed]
    [Google Scholar]
  17. Colpitts CC, Ustinov AV, Epand RF, Epand RM, Korshun VA et al. 5-(Perylen-3-yl)ethynyl-arabino-uridine (aUY11), an arabino-based rigid amphipathic fusion inhibitor, targets virion envelope lipids to inhibit fusion of influenza virus, hepatitis C virus, and other enveloped viruses. J Virol 2013; 87:3640–3654 [View Article][PubMed]
    [Google Scholar]
  18. Gil-Fernández C, García-Villalón D, de Clercq E, Rosenberg I, Holý A. Phosphonylmethoxyalkylpurines and -pyrimidines as inhibitors of African swine fever virus replication in vitro. Antiviral Res 1987; 8:273–281 [View Article][PubMed]
    [Google Scholar]
  19. García-Villalón D, Gil-Fernández C. Antiviral activity of sulfated polysaccharides against African swine fever virus. Antiviral Res 1991; 15:139–148 [View Article][PubMed]
    [Google Scholar]
  20. Fabregas J, García D, Fernandez-Alonso M, Rocha AI, Gómez-Puertas P et al. In vitro inhibition of the replication of haemorrhagic septicaemia virus (VHSV) and African swine fever virus (ASFV) by extracts from marine microalgae. Antiviral Res 1999; 44:67–73 [View Article][PubMed]
    [Google Scholar]
  21. Hurtado C, Bustos MJ, Sabina P, Nogal ML, Granja AG et al. Antiviral activity of lauryl gallate against animal viruses. Antivir Ther 2008; 13:909–917[PubMed]
    [Google Scholar]
  22. Hernáez B, Tarragó T, Giralt E, Escribano JM, Alonso C. Small peptide inhibitors disrupt a high-affinity interaction between cytoplasmic dynein and a viral cargo protein. J Virol 2010; 84:10792–10801 [View Article][PubMed]
    [Google Scholar]
  23. Galindo I, Hernáez B, Berná J, Fenoll J, Cenis JL et al. Comparative inhibitory activity of the stilbenes resveratrol and oxyresveratrol on African swine fever virus replication. Antiviral Res 2011; 91:57–63 [View Article][PubMed]
    [Google Scholar]
  24. Mottola C, Freitas FB, Simões M, Martins C, Leitão A et al. In vitro antiviral activity of fluoroquinolones against African swine fever virus. Vet Microbiol 2013; 165:86–94 [View Article][PubMed]
    [Google Scholar]
  25. Hakobyan A, Arabyan E, Avetisyan A, Abroyan L, Hakobyan L et al. Apigenin inhibits African swine fever virus infection in vitro. Arch Virol 2016; 161:3445–3453 [View Article][PubMed]
    [Google Scholar]
  26. Ziem B, Rahn J, Donskyi I, Silberreis K, Cuellar L et al. Polyvalent 2D entry inhibitors for pseudorabies and African swine fever virus. Macromol Biosci 2017; 17:1600499 [View Article][PubMed]
    [Google Scholar]
  27. Orlov AA, Chistov AA, Kozlovskaya LI, Ustinov AV, Korshun VA et al. Rigid amphipathic nucleosides suppress reproduction of the tick-borne encephalitis virus. Med Chem Commun 2016; 7:495–499 [Crossref]
    [Google Scholar]
  28. de León P, Bustos MJ, Carrascosa AL. Laboratory methods to study African swine fever virus. Virus Res 2013; 173:168–179 [View Article][PubMed]
    [Google Scholar]
  29. Vigant F, Hollmann A, Lee J, Santos NC, Jung ME et al. The rigid amphipathic fusion inhibitor dUY11 acts through photosensitization of viruses. J Virol 2014; 88:1849–1853 [View Article][PubMed]
    [Google Scholar]
  30. Gómez-Puertas P, Rodríguez F, Oviedo JM, Brun A, Alonso C et al. The African swine fever virus proteins p54 and p30 are involved in two distinct steps of virus attachment and both contribute to the antibody-mediated protective immune response. Virology 1998; 243:461–471 [View Article][PubMed]
    [Google Scholar]
  31. García-Escudero R, Andrés G, Almazán F, Viñuela E. Inducible gene expression from African swine fever virus recombinants: analysis of the major capsid protein p72. J Virol 1998; 72:3185–3195[PubMed]
    [Google Scholar]
  32. Fatma N, Panda M, Ansari WH, Kabir-ud-Din. Solubility enhancement of anthracene and pyrene in the mixtures of a cleavable cationic gemini surfactant with conventional surfactants of different polarities. Colloids Surf A Physicochem Eng Asp 2015; 467:9–17 [View Article]
    [Google Scholar]
  33. Yadav T, Tikariha D, Lakra J, Satnami ML, Tiwari AK et al. Solubilization of polycyclic aromatic hydrocarbons in structurally different gemini and monomeric surfactants: a comparative study. J Mol Liq 2015; 204:216–221 [View Article]
    [Google Scholar]
  34. Carrascosa AL, Bustos MJ, de Leon P. Methods for growing and titrating African swine fever virus: field and laboratory samples. Curr Protoc Cell Biol 2011 Chapter 26:Unit 26.14 [View Article][PubMed]
    [Google Scholar]
  35. Chistov AA, Kutyakov SV, Guz AV, Mikhura IV, Ustinov AV et al. Improved large-scale synthesis of 5-(Perylen-3-ylethynyl)-arabino-uridine (aUY11), the Broad-spectrum antiviral. Org Prep Proced Int 2017; 49:377–381 [View Article]
    [Google Scholar]
  36. King DP, Reid SM, Hutchings GH, Grierson SS, Wilkinson PJ et al. Development of a TaqMan PCR assay with internal amplification control for the detection of African swine fever virus. J Virol Methods 2003; 107:53–61 [View Article][PubMed]
    [Google Scholar]
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