Identification of a novel inhibitor targeting influenza A virus group 2 hemagglutinins.
Identification of a novel inhibitor targeting influenza A virus group 2 hemagglutinins.
复制标题
一种新型甲型流感病毒2组血凝素抑制剂的鉴定。
DOI：
10.1016/j.antiviral.2021.105013
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发表时间：
2021-03
影响因子：
7.6
通讯作者：
Rong L
中科院分区：
文献类型：
--
作者：
Du R;Cheng H;Cui Q;Peet NP;Gaisina IN;Rong L
甲型流感病毒（IAV）引起季节性流行病和偶尔但毁灭性的大流行，这是主要的公共卫生问题。推定的抗病毒治疗剂可用于治疗流感，然而，出现的耐药菌株需要不断寻找新的候选药物。在这里，我们报告了一种新的抗病毒剂，化合物CBS1194，这是确定了一个平行的高通量筛选（HTS）活动使用两个逆转录病毒假型轴承H7或H5血凝素（HA）。随后的分析表明，CBS 1194对第2组的IAV具有特异性，而对第1组的IAV没有影响。在添加时间测定中，CBS1194在病毒感染的早期阶段显示出显著的抑制作用。此外，HA介导的溶血可被CBS1194处理抑制，表明该化合物可能靶向负责膜融合的HA茎区。逃逸突变体分析和计算机对接进一步揭示了CBS1194适合融合肽附近的口袋，引起空间位阻，阻断低pH诱导的HA重排。总之，我们的研究确定了一种新的2组IAV融合抑制剂，其具有作为进一步开发的先导化合物的潜力。
Influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are major public health concerns. The putative antiviral therapeutics are useful for the treatment of influenza, however, the emerging resistant strains necessitate a constant search for new drug candidates. Here we report the discovery of a novel antiviral agent, compound CBS1194, which was identified by a parallel high-throughput screening (HTS) campaign using two retroviral pseudotypes bearing H7 or H5 hemagglutinins (HAs). Subsequent analyses demonstrated that CBS1194 is specific to IAVs of group 2, while it has no effect against those of group 1. In a time-of-addition assay, CBS1194 showed a significant inhibitory effect during the early phase of viral infection. In addition, HA-mediated hemolysis can be inhibited by CBS1194 treatment, indicating that this compound may target the HA stalk region, which is responsible for membrane fusion. Escape mutant analyses and in silico docking further revealed that CBS1194 fits into a pocket near the fusion peptide, causing steric hindrance that blocks the low-pH induced rearrangement of HA. In summary, our study identifies a novel fusion inhibitor of group 2 IAVs, which has the potential as lead compound for further development.
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影响因子：
6.7
作者：
Tong S;Zhu X;Li Y;Shi M;Zhang J;Bourgeois M;Yang H;Chen X;Recuenco S;Gomez J;Chen LM;Johnson A;Tao Y;Dreyfus C;Yu W;McBride R;Carney PJ;Gilbert AT;Chang J;Guo Z;Davis CT;Paulson JC;Stevens J;Rupprecht CE;Holmes EC;Wilson IA;Donis RO
通讯作者：
Donis RO
DOI：
10.1073/pnas.1811345115
发表时间：
2018-11-06
影响因子：
11.1
作者：
Goldhill DH;Te Velthuis AJW;Fletcher RA;Langat P;Zambon M;Lackenby A;Barclay WS
通讯作者：
Barclay WS
影响因子：
7.3
作者：
Gaisina IN;Peet NP;Cheng H;Li P;Du R;Cui Q;Furlong K;Manicassamy B;Caffrey M;Thatcher GRJ;Rong L
通讯作者：
Rong L
影响因子：
5.4
作者：
Basu, Arnab;Antanasijevic, Aleksandar;Bowlin, Terry L.
通讯作者：
Bowlin, Terry L.
影响因子：
5.4
作者：
Plotch, SJ;O'Hara, B;Gluzman, Y
通讯作者：
Gluzman, Y