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

• Published in: Antiviral research 1999-09, Vol.43 (2), p.67-78
• Main Authors: Piraino, Frank, Brandt, Curtis R
• Format: Article
• Language: English
• Subjects: Agaricales - metabolism; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral; Antiviral agents; Antiviral Agents - chemistry; Antiviral Agents - isolation & purification; Antiviral Agents - pharmacology; Biological and medical sciences; Disease Models, Animal; DNA Viruses - drug effects; Fungal Proteins - chemistry; Fungal Proteins - drug effects; Fungal Proteins - isolation & purification; Fungal Proteins - pharmacology; General pharmacology; Herpes simplex virus; Herpes simplex virus 1; Herpes simplex virus 2; Herpesvirus 1, Human - drug effects; Herpesvirus 1, Human - physiology; Herpesvirus 2, Human - drug effects; Herpesvirus 2, Human - physiology; Humans; Influenza A virus; Inhibitory Concentration 50; Keratitis, Herpetic - drug therapy; Keratitis, Herpetic - virology; Medical sciences; Mice; Microbial Sensitivity Tests; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Protein; Respiratory syncytial virus; RNA Viruses - drug effects; Rozites caperata; Varicella-zoster virus; Virus Replication - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/S0166-3542(99)00035-2

A protein of 10 425 Da was purified from the edible mushroom Rozites caperata and shown to inhibit herpes simplex virus types 1 and 2 replication with an IC 50 value of ≤5 μM. The protein designated RC-183 also significantly reduced the severity of HSV-1 induced ocular disease in a murine model of keratitis, indicating in vivo efficacy. HSV mutants lacking ribonucleotide reductase and thymidine kinase were also inhibited, suggesting the mechanism does not involve these viral enzymes. Antiviral activity was also seen against varicella zoster virus, influenza A virus, and respiratory syncytial virus, but not against adenovirus type VI, coxsackie viruses A9 and B5, or human immunodeficiency virus. Characterization of RC-183 by mass spectroscopy, sequencing, and other methods suggests it is composed 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 known sequence. Thus, RC-183 is a novel antiviral that may have clinical utility or serve as a lead compound for further development. Determining the mechanism of action may lead to identification of novel steps in viral replication.