Evaluation of the Antiviral Activity Against Junin Virus of Macrocyclic Trichothecenes Produced by the Hypocrealean Epibiont of Baccharis coridifolia

Abstract

Four macrocyclic trichothecenes, roridin A, roridin E, verrucarin A and verrucarin J, produced by the hypocrealean epibiont of Baccharis coridifolia, were evaluated for their inhibitory activity against the arenavirus Junin (JUNV), the etiological agent of Argentine hemorrhagic fever. The trichothecenes achieved a dose-dependent inhibition of JUNV multiplication at concentrations not affecting cell viability. The 50 % inhibitory concentration (IC₅₀) values determined by a virus yield inhibition assay were in the range 1.2 - 4.9 ng/ml. The most active compound was verrucarin J which reduced JUNV yield more than 2 log units and had a similar effect against the arenavirus Tacaribe. The trichothecenes lacked virucidal effects on JUNV virions. From time of addition and removal experiments, it can be concluded that verrucarin J inhibited a late stage in the replicative cycle of JUNV, after 5 h of adsorption.

Trichothecenes - Junin virus - arenaviruses - antiviral activity - Baccharis coridifolia - Asteraceae

References

• 1 Jarvis B B, Midiwo J O, Bean G A, Aboul-Nasr M B, Barros C S. The mystery of trichothecene antibiotics in Baccharis species.  Journal of Natural Products. 1988;  51 736-44
• 2 Isaka M, Punya J, Lertwerawat Y, Tanticharoen M, Thebtaranonth Y. Antimalarial activity of macrocyclic trichothecenes isolated from the fungus Myrothecium verrucaria .  Journal of Natural Products. 1999;  62 329-31
• 3 Kupchan S M, Streelman D R, Jarvis B B, Dailey RG J r, Sneden A T. Isolation of potent new antileukemic trichothecenes from B. megapotamica .  Journal of Organic Chemistry. 1977;  42 4221-5
• 4 Hughes B J, Hsieh G C, Jarvis B B, Sharma R P. Effects of macrocyclic trichothecene mycotoxins on the murine immune system.  Archives of Environmental Contamination and Toxicology. 1989;  3 88-95
• 5 Okazaki K, Kimura S, Yoshizawa T. Antiviral activity of T-2 toxin and related compounds against Herpes simplex virus type 2 in vitro .  Proceedings of the Japan Association of Mycotoxicology. 1988;  No. 28 11-5
• 6 Okazaki K, Yoshizawa T, Kimura S. Antiviral activity of macrocyclic trichothecene mycotoxins and related compounds baccharinoids B-4 and B-5 against Herpes simplex virus type 2.  Agricultural Biological Chemistry. 1989;  53 1441-3
• 7 Tani N, Dohi Y, Onji Y. Yonemasu K. Antiviral activity of trichothecene mycotoxins (deoxynivalenol, fusarenon-X, and nivalenol) against Herpes simplex virus types 1 and 2.  Microbiology and Immunology. 1995;  39 635-7
• 8 Rosso L, Maier M S, Bertoni M D. Trichothecenes production by the hypocrealean epibiont of Baccharis coridifolia .  Plant Biology. 2000;  2 684-6
• 9 Weissenbacher M C, Laguens R P, Coto C E. Argentine hemorrhagic fever.  Current Topics of Microbiology and Immunology. 1987;  134 79-116
• 10 Andrei G, De Clercq E. Inhibitory effect of selected antiviral compounds on arenavirus replication in vitro .  Antiviral Research. 1990;  14 287-300
• 11 Candurra N A, Maskin L, Damonte E B. Inhibition of arenavirus multiplication in vitro by phenotiazines.  Antiviral Research. 1996;  31 149-58
• 12 Candurra N A, Damonte E B. Acción inhibitoria de la cafeína sobre la multiplicación del virus Junín.  Revista Argentina de Microbiología. 1999;  31 135-41
• 13 Cordo S M, Candurra N A, Damonte E B. Myristic acid analogs are inhibitors of junin virus replication.  Microbes and Infection. 1999;  1 609-14
• 14 Maiztegui J I, Fernandez N J, de Damilano A J. Efficacy of immune plasma in treatment of Argentine hemorrhagic fever and association between treatment and late neurological symdrome.  Lancet. 1979;  ii 8154 1216-7
• 15 Enria D A, Briggiler A M, Fernandez N J, Levis S C, Maiztegui J I. Importance of dose of neutralizing antibodies in treatment of Argentine hemorrhagic fever with immune plasma.  Lancet. 1984;  ii 8397 255-6
• 16 Enria D A, Maiztegui J I. Antiviral treatment of Argentine hemorrhagic fever.  Antiviral Research. 1994;  23 23-31
• 17 Contigiani M S, Sabattini M S. Virulencia diferencial de cepas de virus Junín por marcadores biológicos en ratones y cobayos.  Medicina (Bs. Aires). 1977;  37 (Suppl. 3) 244-51
• 18 Downs W G, Anderson C R, Spence L, Aitken T HG, Greenhall A H. Tacaribe virus, a new agent isolated from artibeus bats and mosquitoes in Trinidad, West Indies.  American Journal of Tropical Medicine and Hygiene. 1963;  12 640-6
• 19 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  Journal of Immunological Methods. 1983;  65 55-63
• 20 López N, Scolaro L, Rossi C, Jácamo R, Candurra N, Pujol C . et al . Homologous and heterologous glycoproteins induce protection against Junin virus challenge in guinea pigs.  Journal of General Virology. 2000;  81 273-81
• 21 Mongelli E, Desmarchelier C, Rodriguez Talou J, Coussio J, Ciccia G. In vitro antioxidant and cytotoxic activity of extracts of Baccharis coridifolia DC.  Journal of Ethnopharmacology. 1997;  58 157-63