Abstract
Noroviruses are now recognized as the major cause of acute gastroenteritis in the developed world, yet our ability to prevent and control infection is limited. Recent work has highlighted that, while typically an acute infection in the population, immunocompromised patients often experience long-term infections that may last many years. This cohort of patients and those regularly exposed to infectious material, for example, care workers and others, would benefit greatly from the development of a vaccine or antiviral therapy. While a licensed vaccine or antiviral has yet to be developed, work over the past 10 years in this area has intensified and trials with a vaccine candidate have proven promising. Numerous antiviral targets and small molecule inhibitors that have efficacy in cell culture have now been identified; however, further studies in this area are required in order to make these suitable for clinical use.
Highlights
Current & future antiviral approaches for the control of noroviruses Norovirus replication & life cycle Antiviral strategies against human noroviruses (HuNoVs) can target many aspects of the virus life cycle; viral pro teins or cellular proteins directly, or processes required for virus replication (Figure 1, Tables 1 & 2)
HuNoV VPg is known to interact with eIF3 and components of the eIF4F complex, a pos sible approach would consist of targeting either of these interactions with small molecules that disrupt their interaction with the norovirus VPg protein but not host cell factors
The use of siRNA molecules to target replication is more efficient than Peptideconjugated PMOs (PPMOs); PPMOs and siRNAs targeting the equivalent genomic sequence in feline calicivirus (FCV) showed that siRNA elicited inhibition 50-fold larger than PPMOs [50]
Summary
Noroviruses are recognized as the major cause of acute gastroenteritis in the developed world, yet our ability to prevent and control infection is limited. Research in the area of norovirus vaccines and antivirals has increased in intensity in the past 10 years This is at least partly due to better surveillance mechanisms, improving our under standing of the disease burden, and due to the availability of assays to study the develop ment of the immune response and the efficacy of small molecule inhibitors. The error prone replica tion results in rapid evolution and the generation of new antigenic variants leading to increased diversity and the rapid emergence of new strains capable of evading any herd immunity [9] Despite these difficulties, substantial efforts have been placed on the generation of control measures, treatments and vaccines, with recent developments in these areas reviewed below. The development of vaccines against HuNoV is clearly achievable; USP* 14 L*a DD*X3 elF3 elF4F
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