Antimicrobial peptides as microbicidal contraceptives: prophecies for prophylactics--a mini review

The global increase in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and sexually transmitted infections (STIs) has led to the introduction of barrier methods, such as condoms. However, drawbacks associated with condoms, such as men being reluctant to use them and women being unable to negotiate their use, have led to the search for better and acceptable alternatives, namely the microbicides. These are gel formulations that, when used prior to sexual intercourse, protect against the transmission of HIV and other STIs. However, after observing the side-effects of nonoxynol-9, a component of the microbicidal formulations available on the market, the focus has shifted to natural available compounds demonstrating the preferred protective effects. Antimicrobial peptides (AMPs) are one such group of compounds present in a wide range of organisms from bacteria to humans. The existing 750 or so, low-molecular-weight, cationic charged peptides are classified into five major groups based on their three-dimensional structure obtained by nuclear magnetic resonance studies. The hypothesized mode of action seems to be the interaction of the positively charged peptides with the negatively charged phospholipids present on the surface of the cell membrane. Various studies have demonstrated the effect of several AMPs, namely, defensins, protegrins, cathelicidins, cecropins, polyphemusins, magainins and melittins, against various STI-causing pathogens and HIV/herpes simplex virus, both in vitro and in vivo. The contraceptive efficacies of magainin and nisin in vitro and in vivo are worth mentioning. We believe these peptides are suitable candidates in the development of newer mechanism-based microbicides in future.