Antiviral activity of nucleoside analogues against norovirus.

ABSTRACT:

Background

Norovirus (NoV) is the leading cause of epidemic gastroenteritis worldwide. The lack of a cell culture has significantly hampered the development of effective therapies against human NoV. Clinically approved nucleoside and non-nucleoside analogues have been used successfully against RNA viruses.

Methods

In this study, we evaluated the efficacy of four nucleoside analogues (2'-C-MeC, 2'-F-2'-C-MeC, ?-D-N(4)-hydroxycytidine [NHC] and lamivudine) on Norwalk virus (NV) RNA levels and protein expression in NV replicon-harbouring cells (HG23 cells), and their efficacy in blocking murine norovirus (MNV) replication in RAW 264.7 cells.

Results

2'-C-MeC and 2'-F-2'-C-MeC reduced MNV RNA levels and infectivity in RAW 264.7 cells in a concentration- and time-dependent manner. The median effective concentrations (EC(50)) of 2'-C-MeC and 2'-F-2'-C-MeC were 6.9 ?M and 12.7 ?M, respectively. 2'-C-MeC, 2'-F-2'-C-MeC and NHC reduced NV RNA levels and protein expression in HG23 cells. For the NV replicon, the EC(50) of 2'-C-MeC (1.3 ?M) was comparable to the antiviral activity of NHC (1.5 ?M) and twofold more potent than 2'-F-2'-C-MeC (3.2 ?M). The combination of 2'-C-MeC/ribavirin resulted in modest synergistic activity, whereas NHC/ribavirin was antagonistic for NV replication in HG23 cells.

Conclusions

The antiviral activity of 2'-C-MeC against strains of two different NoV genogroups and the low EC(50) suggest that this nucleoside analogue may be effective against the more prevalent GII NoVs. In the absence of a vaccine, antiviral agents could be an effective intervention to control the spread of human NoV in populations at a high risk for NoV disease.

SUBMITTER: Costantini VP 

PROVIDER: S-EPMC7751060 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature