Antiviral Activity of Antibiotic Peptaibols, Chrysospemins B and D, Produced by Apiocrea sp. 14T against TMV Infection

A total of about 300 fungal isolates from forest havitats were screened for inhibitors of tobacco mosaic virus (TMV) infection using its local lesion host, Nicotiana tabacum cv. Xanthi nc. Ine of the isolates, 14T, showed a strong activity against TMV infection, and was identified as an Apiocrea sp. based on its morphological characterstics. Rice was an optimum culture medium for its fermentation, and two antiviral compounds, KGT 141 and KGT 142, were resolved from the rice culture through column chromatography, TLC, and HPLC. By NMR and FAB-MS, the two compounds were identified as chrysospermins B (KGT 141) and D (KGT 142), both of which are peptaibols with 19-mer amino acids possessing an acetylated N-terminus and a hydroxy-amino acid (tryptophanol) at the C-terminus. Both compounds showed inhibitory activities against TMV infection, but chrysospermin D showed the stronger activity than chrysospermin B. The former of $100{\;}\mu\textrm{g}/ml$ and 54.7% at $10{\;}\mu\textrm{g}/ml$, respectively. Furthermore, the chrysospermins were highly cytotoxic toward cancer cell lines of PC-3 (prostrate) and K562 (leukemia), and inhibited growth of the Gram-positive bacteria tested, especially the plant pathogenic bacterium Corynebacterium lilium. To the best of our knowledge, this is the first report on the inhibition of plant virus infection by antimicrobial peptaibols.