Abstract
Noroviruses are the main causative agents of acute viral gastroenteritis worldwide. However, no vaccine or specific antiviral treatment is available, imposing a heavy global health burden. The nucleoside analogue 2’-fluoro-2’-deoxycytidine (2’-FdC) has been reported to have broad antiviral activity. Here, we report that 2’-FdC significantly inhibits murine norovirus replication in macrophages. This effect was partially reversed by exogenous supplementation of cytidine triphosphate. The combination of 2’-FdC with mycophenolic acid, ribavirin or favipiravir (T705) exerts synergistic antiviral effects. These results indicate that 2’-FdC is a potential candidate for antiviral drug development against norovirus infection.
Highlights
Human norovirus (HuNV) is a non-enveloped, positive single-stranded RNA virus [1]
Norovirus gastroenteritis is usually self-limiting, it has been recognized as an emerging burden in immunocompromised populations, transplant recipients [5, 6]
Murine norovirus (MNV), which is capable of replicating in both cell culture and small-animal models, shares similar
Summary
Human norovirus (HuNV) is a non-enveloped, positive single-stranded RNA virus [1]. Noroviruses have been classified into at least 10 genogroups (GI-GX) on the basis of the amino acid sequence diversity of the viral VP1 protein [2]. Viruses in the GI, GII, GIV, GVIII and GIX genogroups can infect humans and are a major cause of acute epidemic viral gastroenteritis worldwide [2]. It is estimated that noroviruses are responsible for 699 million gastroenteritis cases per year [3] and 200,000 deaths in children under 5 years of age in developing countries [4]. Research into HuNV infection has been hampered by the lack of availability of robust experimental models sustaining viral infection. Murine norovirus (MNV), which is capable of replicating in both cell culture and small-animal models, shares similar
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