Grape seed extract (GSE) is reported to have many pharmacological benefits, including antioxidant, antiinflammatory, anticarcinogenic, and antimicrobial properties. However, the effect of this inexpensive rich source of natural phenolic compounds on human enteric viruses has not been well documented. In the present study, the effect of commercial GSE, Gravinol-S, on the infectivity of human enteric virus surrogates (feline calicivirus, FCV-F9; murine norovirus, MNV-1; and bacteriophage MS2) and hepatitis A virus (HAV; strain HM175) was evaluated. GSE at concentrations of 0.5, 1, and 2 mg/ml was individually mixed with equal volumes of each virus at titers of ϳ7 log 10 PFU/ml or ϳ5 log 10 PFU/ml and incubated for 2 h at room temperature or 37°C. The infectivity of the recovered viruses after triplicate treatments was evaluated by standardized plaque assays. At high titers (ϳ7 log 10 PFU/ml), FCV-F9 was significantly reduced by 3.64, 4.10, and 4.61 log 10 PFU/ml; MNV-1 by 0.82, 1.35, and 1.73 log 10 PFU/ml; MS2 by 1.13, 1.43, and 1.60 log 10 PFU/ml; and HAV by 1.81, 2.66, and 3.20 log 10 PFU/ml after treatment at 37°C with 0.25, 0.50, and 1 mg/ml GSE, respectively (P < 0.05) in a dose-dependent manner. GSE treatment of low titers (ϳ5 log 10 PFU/ml) at 37°C also showed viral reductions. Room-temperature treatments with GSE caused significant reduction of the four viruses, with higher reduction for low-titer FCV-F9, MNV-1, and HAV compared to high titers. Our results indicate that GSE shows promise for application in the food industry as an inexpensive novel natural alternative to reduce viral contamination and enhance food safety.Grapes are one of the world's leading fruit crops, with production rates at more than 50 million tons a year (34). Grape seeds, which are by-products of wine and the grape juice industries, are shown to contain large quantities of phenolic compounds such as gallic acid and monomeric flavan-3-ols catechin, epicatechin, gallocatechin, epigallocatechin, and epicatechin-3-O-gallate, as well as dimeric, trimeric, and polymeric proanthocyanidins (PAC) (37). Grape seed extract (GSE) reportedly has many pharmacological and health benefits that include antioxidant, cardioprotective, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, anticarcinogenic, and antiaging effects (28,47,48).Recently, GSE has gained increasing attention in the food industry because of its associated antimicrobial properties. Rhodes et al. (31) showed that GSE at a concentration of 0.25 mg/ml decreased Listeria monocytogenes from 10 6 to 10 7