Gingipains are the major virulence factors of Porphyromonas gingivalis, the main periodontopathogen. It is expected that inhibition of gingipain activity in vivo could prevent or slow down the progression of adult periodontitis. To date, several classes of gingipain inhibitors have been recognized. These include gingipain N-terminal prodomains, synthetic compounds, inhibitors from natural sources, antibiotics, antiseptics, antibodies, and bacteria. Several synthetic compounds are potent gingipain inhibitors but inhibit a broad spectrum of host proteases and have undesirable side effects. Synthetic compounds with high specificity for gingipains have unknown toxicity effects, making natural inhibitors more promising as therapeutic gingipain blockers. Cranberry and rice extracts interfere with gingipain activity and prevent the growth and biofilm formation of periodontopathogens. Although the ideal gingipain inhibitor has yet to be discovered, gingipain inhibition represents a novel approach to treat and prevent periodontitis. Gingipain inhibitors may also help treat systemic disorders that are associated with periodontitis, including cardiovascular disease, rheumatoid arthritis, aspiration pneumonia, pre-term birth, and low birth weight.
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