Highlights
• Renilla luciferase-based MVEV sub-genomic replicon was constructed and applied in antiviral drug evaluation.
• Removal of Stem Loop I from 3’UTR impairs viral genome replication.
• Asunaprevir and ribavirin exhibit synergistic antiviral activity against MVEV.
• A single-round MVEV infectious particle platform was developed.
Abstract
Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus known for causing severe neurological diseases in humans. Despite the rising number of reported infections and high mortality rate among hospitalized patients, no antiviral therapies or licensed vaccines are available. To strengthen preparedness against this reemerging virus, we establish a subgenomic replicon (SGR) platform and a complementary single-round infectious particles (SRIPs) production system, using widely circulating genotype 1 (G1) MVEV as backbone. Stem-loop I(SLI) from 3’UTR stands for the major difference among 4 MVEV genotypes and removal of SLI resulted in mild decrease of genome replication. Through screening a mini anti-flavivirus drug library, we identified that asunaprevir (ASV) and ribavirin (RBV) inhibit MVEV infection independently. Combination of ASV and RBV also showed synergistic activity against MVEV. These results underscore the value of the MVEV replicon system as a versatile tool for evaluating antiviral compounds, supporting the potential of ASV and RBV as a combinatorial therapeutic approach.
Source:
Link: https://www.sciencedirect.com/science/article/abs/pii/S0166354226001567?via%3Dihub
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