SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago)

• Published in: Phytomedicine (Stuttgart) Vol. 1; no. 2; p. 77
• Main Authors: Ubillas, R, Jolad, S D, Bruening, R C, Kernan, M R, King, S R, Sesin, D F, Barrett, M, Stoddart, C A, Flaster, T, Kuo, J, Ayala, F, Meza, E, Castañel, M, McMeekin, D, Rozhon, E, Tempesta, M S, Barnard, D, Huffman, J, Smee, D, Sidwell, R, Soike, K, Brazier, A, Safrin, S, Orlando, R, Kenny, P T, Berova, N, Nakanishi, K
• Format: Journal Article
• Language: English
• Published: Germany 01.09.1994
• ISSN: 0944-7113
• DOI: 10.1016/S0944-7113(11)80026-7

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.