Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.
Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):2128-2138. doi: 10.1080/14756366.2021.1982932.
Influenza viruses represent a major threat to human health and are responsible for seasonal epidemics, along with pandemics. Currently, few therapeutic options are available, with most drugs being at risk of the insurgence of resistant strains. Hence, novel approaches targeting less explored pathways are urgently needed. In this work, we assayed a library of nitrobenzoxadiazole derivatives against the influenza virus A/Puerto Rico/8/34 H1N1 (PR8) strain. We identified three promising 4-thioether substituted nitrobenzoxadiazoles (, , and ) that were able to inhibit viral replication at low micromolar concentrations in two different infected cell lines using a haemagglutination assay. We further assessed these molecules using an In-Cell Western assay, which confirmed their potency in the low micromolar range. Among the three molecules, and displayed the most favourable profile of activity and selectivity and were selected as hit compounds for future optimisation studies.
流感病毒对人类健康构成重大威胁，可导致季节性流行疫情和大流行疫情。目前，可供选择的治疗方法有限，大多数药物都面临耐药菌株出现的风险。因此，迫切需要针对研究较少的途径的新方法。在这项工作中，我们针对流感病毒 A/Puerto Rico/8/34 H1N1 (PR8) 株对硝基苯并二唑衍生物文库进行了检测。我们发现了三种有前途的 4-硫醚取代的硝基苯并二唑（、和），它们能够在两种不同的感染细胞系中通过血凝试验以低微摩尔浓度抑制病毒复制。我们进一步使用细胞内 Western 检测法评估了这些分子，结果证实它们在低微摩尔范围内具有很强的活性。在这三种分子中，和表现出最有利的活性和选择性特征，被选为进一步优化研究的候选化合物。
