Prophylactic treatment with the nucleoside analogue 2′-C-methylcytidine completely prevents transmission of norovirus

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Abstract

Objectives

Norovirus outbreaks of acute gastroenteritis are highly prevalent, extensive and can disturb the functioning of health institutions, leading to the closure of hospital wards and causing life-threatening infections in long-term care facilities. There is no vaccine available; hence there is a pressing need for antivirals for the treatment (in immunodeficient patients) and prophylaxis of norovirus infections. We explored in a mouse model whether an inhibitor of norovirus replication can prevent/reduce transmission of the virus.

Methods

We reported recently that the viral polymerase inhibitor 2′-C-methylcytidine (2CMC) efficiently protects against murine norovirus (MNV)-induced diarrhoea and mortality in mice. Here, we established an MNV-transmission model, determined the 50% infectious dose and assessed the ability of an antiviral molecule to prevent or reduce transmission of (murine) norovirus when given either to the infected (seeder) mice or to the uninfected (sentinel) mice.

Results

A robust norovirus transmission model was established using genogroup V (murine) norovirus in AG129 mice. The 50% infectious dose was determined to be ∼270 CCID50 (50% cell culture infectious dose). Treatment of infected mice with 2CMC reduced viral shedding and markedly reduced transmission to uninfected sentinels. Also, prophylactic treatment of sentinels with 2CMC resulted in protection against infection with MNV.

Conclusions

These findings constitute an important first step towards developing an efficient prophylaxis for the control of norovirus outbreaks.

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