Screening antivirals with a mCherry-expressing recombinant bovine respiratory syncytial virus: a proof of concept using cyclopamine

使用表达 mCherry 的重组牛呼吸道合胞病毒筛选抗病毒药物:使用环巴胺进行概念验证

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作者:Jenna Fix, Delphyne Descamps, Marie Galloux, Cécile Ferret, Edwige Bouguyon, Siamak Zohari, Katarina Näslund, Sara Hägglund, Ralf Altmeyer, Jean-François Valarcher, Sabine Riffault, Jean-François Eléouët

Abstract

Bovine respiratory syncytial virus (BRSV) is a pathogenic pneumovirus and a major cause of acute respiratory infections in calves. Although different vaccines are available against BRSV, their efficiency remains limited, and no efficient and large-scale treatment exists. Here, we developed a new reverse genetics system for BRSV expressing the red fluorescent protein mCherry, based on a field strain isolated from a sick calf in Sweden. Although this recombinant fluorescent virus replicated slightly less efficiently compared to the wild type virus, both viruses were shown to be sensitive to the natural steroidal alkaloid cyclopamine, which was previously shown to inhibit human RSV replication. Our data thus point to the potential of this recombinant fluorescent BRSV as a powerful tool in preclinical drug discovery to enable high throughput compound screening.

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