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 mug/mL. Main Outcome Measures: Effect of PAP on sperm motility, kinematics, and spe rm penetration through bovine mucus, as well as binding, penetration, and f usion of zona-free hamster eggs. Results: Exposing human sperm to PAP (IC50 p24 = 14 +/- 2 nM) did not affec t sperm motility and kinematics over a dose range of 1 to 1,000 mug/mL. Tre ating sperm with either 100 or 1,000 mug/mL of PAP had no effect on cervica l mucus penetrability, nor did it affect sperm binding, penetration, and fu sion of zona-free hamster eggs. PAP was noncytotoxic to genital-tract epith elial cells. Conclusions: The broad-spectrum antiviral agent PAP was nontoxic to human s perm and female genital tract epithelial cells even at a concentration 2,00 0 times higher than its IC50 value against HIV-1. PAP has particular clinic al usefulness both as a nonspermicidal intravaginal microbicide and as a pr ophylactic antiviral agent that can inactivate infective viruses and virus- infected cells in semen before assisted reproductive technology procedures are undertaken. (C) 2001 by American Society Reproductive Medicine.