SP-303, an antiviral oligomeric protanthocyanidinfrom the latex of Croton lechleri (Sangre de Drago)
Document Type
Article
Journal/Book Title/Conference
SP-303, an antiviral oligomeric protanthocyanidinfrom the latex of Croton lechleri (Sangre de Drago)
Volume
1
Publication Date
1994
First Page
77
Last Page
106
Abstract
SP-303, a large proanthocyanidin oligomer isolated from the latex of the plant species Croton lechleri (Eupborbiaceae) has demonstrated broad activity against a variety of DNA and RNA viruses. In cell culture, SP-303 exhibits potent activity against isolates and laboratory strains of respiratory syncytial virus (RSV), influenza A virus (FLU-A) and parainfluenza virus (PIV). Parallel assays of SP-303 and ribavirin showed comparable activity against these viruses. SP-303 also exhibits significant inhibitory activity against herpesvirus (HSV) types 1 and 2, including herpesviruses resistant to acyclovir and foscarnet. Inhibition was also observed against hepatitis A and B viruses. The antiviral mechanism of SP-303 seems to derive from its direct binding to components of the viral envelope, resulting in inhibition of viral attachment and penetration of the plasma membrane. Antiviral effects of SP-303 were measured by three distinct methods: CPE, MTT and precursor uptake/incorporation. Cytotoxicity endpoints were markedly greater than the respective antiviral endpoints. SP-303 exhibited activity in RSV-infected cotton rats and African green monkeys, PIV-3-infected cotton rats, HSV-2 infected mice and guinea pigs and FLU-A-infected mice. The most successful routes of SP-303 administration for producing efficacy were: topical application to HSV-2- genital lesions in mice and guinea pigs, aerosol inhalation to FLU-A-infected mice and PIV-3-infected cotton rats, and oral dosage to RSV-infected cotton rats. A variety of toxicological evaluations demonstrated the safety of SP-303, particularly orally, which was predictable, since condensed tannins are a common dietary component. It is notable that the larger proanthocyanidins as a class have high antiviral activity, whereas most of the monomers are inactive. Clinical trials are ongoing to evaluate SP-303 as a therapeutic antiviral agent.
Recommended Citation
Ubillas, R., S.D. Jolad, R.C. Bruening, M.R. Kernan, S.R. King, D.F. Sesin, M. Barrett, C.A. Stoddart, T. Flaster, J. Kuo, F. Ayala, E. Meza, M. Castanel, D. McMeekin, E. Rozhon, M.S. Tempesta, D. Barnard, D. Smee, R. Sidwell, K. Soike, A. Brazier, S. Safrin, R. Orlando, P.T.M. Kenney, N. Berova, and K. Nakinishi. 1994. SP-303, an antiviral oligomeric protanthocyanidin from the latex of Croton lechleri (Sangre de Drago). Phytomed. 1:77-106.
Comments
Phytomed. 1:77-106