Isolation and partial characterization of an antiviral, RC-183, from the edible mushroom Rozites caperata

A protein of 10425 Da was purified from the edible mushroom Rozites caperat a and shown to inhibit herpes simplex virus types 1 and 2 replication with an IC50 value of less than or equal to 5 mu M. The protein designated RC-18 3 also significantly reduced the severity of HSV-I induced ocular disease i n a murine model of keratitis, indicating in vivo efficacy. HSV mutants lac king ribonucleotide reductase and thymidine kinase were also inhibited, sug gesting the mechanism does not involve these viral enzymes. Antiviral activ ity was also seen against varicella tester virus, influenza A virus, and re spiratory syncytial virus, but not against adenovirus type Vt, coxsackie vi ruses A9 and B5, or human immunodeficiency virus. Characterization of RC-18 3 by mass spectroscopy, sequencing, and other methods suggests it is compos ed of a peptide (12 or 13 mer) coupled to ubiquitin via an isopeptide bond between the c-terminal glycine of ubiquitin and the epsilon amino group of a lysine residue in the peptide. The peptide sequence did not match any kno wn sequence. Thus, RC-183 is a novel antiviral that may have clinical utili ty or serve as a lead compound for further development. Determining the mec hanism of action may lead to identification of novel steps in viral replica tion. (C) 1999 Elsevier Science B.V. All rights reserved.