Dipartimento di Scienze Degli Alimenti e Del Farmaco (DipALIFAR), Università Degli Studi di Parma, Viale Delle Scienze, 27/A, 43124, Parma, Italy.
Institute of Microbiology, University Hospital of Lausanne, University of Lausanne, 1011, Lausanne, Switzerland.
Antiviral Res. 2024 Nov;231:106003. doi: 10.1016/j.antiviral.2024.106003. Epub 2024 Sep 10.
Broad-spectrum antivirals can be extremely important for pandemic preparedness. Targeting host factors dispensable for the host but indispensable for the virus can result in high barrier to resistance and a large range of viruses targeted. PI4KB is a lipid kinase involved in the replication of several RNA viruses, but common inhibitors of this target are mainly active against members of the Picornaviridae family. Herein we describe the optimization of bithiazole PI4KB inhibitors as broad-spectrum antivirals (BSAs) active against different members of the Picornaviridae, Coronaviridae, Flaviviridae and Poxviridae families. Since some of these viruses are transmitted via respiratory route, the efficacy of one of the most promising compounds was evaluated in an airway model. The molecule showed complete viral inhibition and absence of toxicity. These results pave the road for the development of new BSAs.
广谱抗病毒药物对于大流行的防范非常重要。针对宿主中对宿主非必需但对病毒必不可少的宿主因子，可以产生高耐药屏障和广泛的靶向病毒。PI4KB 是一种参与几种 RNA 病毒复制的脂质激酶，但该靶标的常见抑制剂主要对小核糖核酸病毒科的成员具有活性。在此，我们描述了双噻唑 PI4KB 抑制剂作为广谱抗病毒药物（BSA）的优化，这些抑制剂对小核糖核酸病毒科、冠状病毒科、黄病毒科和痘病毒科的不同成员具有活性。由于其中一些病毒通过呼吸道传播，因此评估了其中一种最有前途的化合物在气道模型中的疗效。该分子显示出完全的病毒抑制和无毒性。这些结果为开发新的广谱抗病毒药物铺平了道路。
