FK506, a secondary metabolite produced by Streptomyces, presents a novel antiviral activity against Orthopoxvirus infection in cell culture.
OBJECTIVE
To investigate the antiviral potential of the macrolide FK506, produced by Streptomyces tsukubaensis, against Orthopoxvirus infection in cell culture, and determine the replicative stage of viral cycle affected by the treatment.


RESULTS
Cell lines were infected with different Orthopoxviruses and treated with FK506. The macrolide inhibited the replication of the prototypic Orthopoxvirus, vaccinia virus strain WR, with an IC50 of 12.05 micromol l(-1). Progeny production of other Orthopoxviruses was also inhibited by FK506 at noncytotoxic concentrations, as evaluated by the neutral-red uptake assay and metabolic labelling of cellular proteins. By Western blot assay, we detected a severe inhibition (approximately 87.6% +/- 2.78%) of VV strain WR post-replicative protein synthesis. A similar reduction of virus DNA accumulation, as observed by slot-blot assay, probably accounts for the subsequent inhibition of virus late proteins.


CONCLUSIONS
The macrolide FK506, isolated from S. tsukubaensis, presents a novel anti-poxvirus activity, probably targeting the stage of DNA replication during Orthopoxvirus infection.


CONCLUSIONS
The secondary metabolite FK506, isolated from the culture filtrate of S. tsukubaensis, shows a pleiotropic range of activities, and might be a valuable tool as a lead structure in the generation of non-immunosuppressant analogues with strong anti-poxvirus activity.
Reis
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SA
Laboratório de Biologia Molecular de Vírus, Instituto de Biofísica Carlos Chagas Filho, CCS, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Moussatché
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N
Damaso
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CR
D000818:Animals; D000898:Antibiosis; D000998:Antiviral Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D018155:Orthopoxvirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011213:Poxviridae Infections / Q000188:drug therapy*; D013302:Streptomyces / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D001426:Bacterial Proteins; D004279:DNA, Viral; D016559:Tacrolimus