State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
College of Life Sciences, University of the Chinese Academy of Sciences, Beijing 100049, China.
Viruses. 2022 May 4;14(5):959. doi: 10.3390/v14050959.
Adenoviruses can cause infections in people of all ages at all seasons of the year. Adenovirus infections cause mild to severe illnesses. Children, immunocompromised patients, or those with existing respiratory or cardiac disease are at higher risk. Unfortunately, there are no commercial drugs or vaccines available on the market for adenovirus infections. Therefore, there is an urgent need to discover new antiviral drugs or drug targets for adenovirus infections. To identify potential antiviral agents for adenovirus infections, we screened a drug library containing 2138 compounds, most of which are drugs with known targets and past phase I clinical trials. On a cell-based assay, we identified 131 hits that inhibit adenoviruses type 3 and 5. A secondary screen confirmed the antiviral effects of 59 inhibitors that inhibit the replication of adenoviruses type 3 or 5. Most of the inhibitors target heat shock protein, protein tyrosine kinase, the mTOR signaling pathway, and other host factors, suggesting that these host factors may be essential for replicating adenoviruses. Through this study, the newly identified adenovirus inhibitors may provide a start point for developing new antiviral drugs to treat adenovirus infections. Further validation of the identified drug targets can help the development of new therapeutics against adenovirus infections.
腺病毒可在一年中的任何季节感染所有年龄段的人。腺病毒感染可引起轻度至重度疾病。儿童、免疫功能低下的患者或有现有呼吸道或心脏疾病的患者风险较高。不幸的是，目前市场上尚无针对腺病毒感染的商业药物或疫苗。因此，迫切需要发现针对腺病毒感染的新抗病毒药物或药物靶点。为了鉴定针对腺病毒感染的潜在抗病毒药物，我们筛选了一个包含 2138 种化合物的药物库，其中大多数是具有已知靶点和过去 I 期临床试验的药物。在基于细胞的测定中，我们鉴定出了 131 种抑制腺病毒 3 型和 5 型的化合物。二次筛选证实了 59 种抑制剂对腺病毒 3 型或 5 型复制的抗病毒作用。大多数抑制剂的靶标是热休克蛋白、蛋白酪氨酸激酶、mTOR 信号通路和其他宿主因子，这表明这些宿主因子可能对复制腺病毒至关重要。通过这项研究，新鉴定的腺病毒抑制剂可能为开发治疗腺病毒感染的新型抗病毒药物提供起点。对鉴定的药物靶点的进一步验证有助于开发针对腺病毒感染的新疗法。
