Pokeweed antiviral protein: a potential nonspermicidal prophylactic antiviral agent

OBJECTIVE: To investigate the effects of pokeweed antiviral protein (PAP), a 29-kDa anti-human immunodeficiency virus (HIV) protein purified from the leaves of Phytolacca americana, on human sperm function. DESIGN: Prospective, controlled study. SETTING: Reproductive biology department. PATIENT(S): Seven sperm donors. INTERVENTION(S): Human sperm and female genital tract epithelial cells were exposed to PAP ranging in concentration from 1 to 1,000 microg/mL. MAIN OUTCOME MEASURES: Effect of PAP on sperm motility, kinematics, and sperm penetration through bovine mucus, as well as binding, penetration, and fusion of zona-free hamster eggs. RESULTS: Exposing human sperm to PAP (IC(50) p24 = 14 +/- 2 nM) did not affect sperm motility and kinematics over a dose range of 1 to 1,000 microg/mL. Treating sperm with either 100 or 1,000 microg/mL of PAP had no effect on cervical mucus penetrability, nor did it affect sperm binding, penetration, and fusion of zona-free hamster eggs. PAP was noncytotoxic to genital-tract epithelial cells. CONCLUSIONS: The broad-spectrum antiviral agent PAP was nontoxic to human sperm and female genital tract epithelial cells even at a concentration 2,000 times higher than its IC(50) value against HIV-1. PAP has particular clinical usefulness both as a nonspermicidal intravaginal microbicide and as a prophylactic antiviral agent that can inactivate infective viruses and virus-infected cells in semen before assisted reproductive technology procedures are undertaken.