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鉴定干扰甲型流感病毒进入的新型有效化合物

Identification of Novel and Efficacious Chemical Compounds that Disturb Influenza A Virus Entry .

作者信息

Khalil Hany, El Malah Tamer, El Maksoud Ahmed I Abd, El Halfawy Ibrahim, El Rashedy Ahmed A, El Hefnawy Mahmoud

机构信息

Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat CitySadat, Egypt.

Photochemistry Department, National Research CentreGiza, Egypt.

出版信息

Front Cell Infect Microbiol. 2017 Jun 30;7:304. doi: 10.3389/fcimb.2017.00304. eCollection 2017.

Abstract

Influenza A virus is a negative RNA stranded virus of the family , and represents a major public health threat, compounding existing disease conditions. Influenza A virus replicates rapidly within its host and the segmented nature of its genome facilitates re-assortment, whereby whole genes are exchanged between influenza virus subtypes during replication. Antiviral medications are important pharmacological tools in influenza virus prophylaxis and therapy. However, the use of currently available antiviral is impeded by sometimes high levels of resistance in circulating virus strains. Here, we identified novel anti-influenza compounds through screening of chemical compounds synthesized on human lung epithelial cells. Computational and experimental screening of extensive and water soluble compounds identified novel influenza virus inhibitors that can reduce influenza virus infection without detectable toxic effects on host cells. Interestingly, the indicated active compounds inhibit viral replication most likely via interaction with cell receptors and disturb influenza virus entry into host cells. Collectively, screening of new synthesis chemical compounds on influenza A virus replication provides a novel and efficacious anti-influenza compounds that can inhibit viral replication via disturbing virus entry and indicates that these compounds are attractive candidates for evaluation as potential anti-influenza drugs.

摘要

甲型流感病毒是 科的一种负链 RNA 病毒,是对公共卫生的一大威胁,会使现有疾病状况更加复杂。甲型流感病毒在其宿主体内快速复制,其基因组的分段性质有利于重配,即在复制过程中流感病毒亚型之间交换整个基因。抗病毒药物是流感病毒预防和治疗中的重要药理学工具。然而,目前可用抗病毒药物的使用受到循环病毒株中有时出现的高耐药性的阻碍。在此,我们通过筛选在人肺上皮细胞上合成的化合物,鉴定出新型抗流感化合物。对大量水溶性化合物进行计算和实验筛选,确定了新型流感病毒抑制剂,这些抑制剂可减少流感病毒感染,且对宿主细胞无明显毒性作用。有趣的是,所示活性化合物最有可能通过与细胞受体相互作用来抑制病毒复制,并干扰流感病毒进入宿主细胞。总体而言,对甲型流感病毒复制的新合成化合物进行筛选,提供了一种新型且有效的抗流感化合物,该化合物可通过干扰病毒进入来抑制病毒复制,表明这些化合物是作为潜在抗流感药物进行评估的有吸引力的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93e3/5491913/9d2c26ed1f10/fcimb-07-00304-g0001.jpg

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