Becker Jennifer C, Tollefson Sharon J, Weaver David, Williams John V
1 Department of Pathology, Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
2 Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA.
Antivir Chem Chemother. 2019 Jan-Dec;27:2040206619830197. doi: 10.1177/2040206619830197.
Human metapneumovirus, a paramyxovirus discovered in 2001, is a major cause of lower respiratory infection in adults and children worldwide. There are no licensed vaccines or drugs for human metapneumovirus. We developed a fluorescent, cell-based medium-throughput screening assay for human metapneumovirus that captures inhibitors of all stages of the viral lifecycle except budding of progeny virus particles from the cell membrane. We optimized and validated the assay and performed a successful medium-throughput screening. A number of hits were identified, several of which were confirmed to inhibit viral replication in secondary assays. This assay offers potential to discover new antivirals for human metapneumovirus and related respiratory viruses. Compounds discovered using the medium-throughput screening may also provide useful probes of viral biology.
人偏肺病毒是2001年发现的一种副粘病毒，是全球成人和儿童下呼吸道感染的主要病因。目前尚无针对人偏肺病毒的许可疫苗或药物。我们开发了一种基于细胞的荧光中通量筛选试验，用于检测人偏肺病毒，该试验可捕获病毒生命周期所有阶段的抑制剂，但不包括子代病毒颗粒从细胞膜出芽的阶段。我们对该试验进行了优化和验证，并成功进行了中通量筛选。鉴定出了许多活性化合物，其中几种在二次试验中被证实可抑制病毒复制。该试验为发现针对人偏肺病毒及相关呼吸道病毒的新型抗病毒药物提供了可能。通过中通量筛选发现的化合物也可能为病毒生物学提供有用的探针。
