Abstract
Phytochemicals provide environmentally friendly and relatively inexpensive natural products, which could potentially benefit public health by controlling human norovirus (HuNoV) infection. In this study, 18 different phytochemicals were evaluated for antiviral effects against norovirus using murine norovirus (MNV) as a model for norovirus biology. Among these phytochemicals, curcumin (CCM) was the most potent anti-noroviral phytochemical, followed by resveratrol (RVT). In a cell culture infection model, exposure to CCM or RVT for 3 days reduced infectivity of norovirus by 91% and 80%, respectively. To confirm the antiviral capability of CCM, we further evaluated its antiviral efficacy at various doses (0.25, 0.5, 0.75, 1, and 2 mg/mL) and durations (short-term: 10, 30, 60, and 120 min; long-term: 1, 3, 7, and 14 days). The anti-noroviral effect of CCM was verified to occur in a dose-dependent manner. Additionally, we evaluated the inhibitory effect of each phytochemical on the replication of HuNoV using a HuNoV replicon-bearing cell line (HG23). Neither CCM nor RVT had a strong inhibitory effect on HuNoV replication, which suggests that their antiviral mechanism may involve viral entry or other life cycle stages rather than the replication of viral RNA. Our results demonstrated that CCM may be a promising candidate for development as an anti-noroviral agent to prevent outbreaks of foodborne illness.
Highlights
Human norovirus (HuNoV) is the leading cause of viral gastroenteritis outbreaks worldwide [1,2,3].Clinical symptoms of human norovirus (HuNoV) infection include vomiting, nausea, and diarrhea within 24–48 h of infection [4]
Cultivation methods for HuNoV using B cells [21] or isolated enterocytes [22] were reported recently. Those findings are very meaningful and can be a milestone to decipher the mechanisms of norovirus infection at a molecular level, it is a bit early to apply the methods to screening various antiviral compounds
The replication of HuNoV in a B-cell culture system did not appear to be robust, as observed in murine norovirus (MNV) [23], and the methods need to be validated with different types of HuNoV in other laboratories
Summary
Human norovirus (HuNoV) is the leading cause of viral gastroenteritis outbreaks worldwide [1,2,3]. Clinical symptoms of HuNoV infection include vomiting, nausea, and diarrhea within 24–48 h of infection [4]. HuNoV has low infectious doses of ~10 viral particles and is highly infectious to susceptible individuals. Due to the current lack of a HuNoV vaccine, preventive measures are the most effective way to reduce outbreaks of HuNoV, which is known to be resistant to environmental stresses [10,11]. Current prevention methods for HuNoV include promoting personal hygiene for food handlers to avoid noroviral contamination and inactivation of infectious viral particles [12,13]. Inactivation of Molecules 2016, 21, 1401; doi:10.3390/molecules21101401 www.mdpi.com/journal/molecules
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