Anti-rheumatic colchicine phytochemical exhibits potent antiviral activities against avian and seasonal Influenza A viruses (IAVs) via targeting different stages of IAV replication cycle.
Anti-rheumatic colchicine phytochemical exhibits potent antiviral activities against avian and seasonal Influenza A viruses (IAVs) via targeting different stages of IAV replication cycle.
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DOI：
10.1186/s12906-023-04303-2
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发表时间：
2024-01-22
影响因子：
3.9
通讯作者：
Mostafa, Ahmed
中科院分区：
文献类型：
--
作者：
Hegazy, Akram;Soltane, Raya;Alasiri, Ahlam;Mostafa, Islam;Metwaly, Ahmed M.;Eissa, Ibrahim H.;Mahmoud, Sara H.;Allayeh, Abdou Kamal;Shama, Noura M. Abo;Khalil, Ahmed A.;Barre, Ramya S.;El-Shazly, Assem Mohamed;Ali, Mohamed A.;Martinez-Sobrido, Luis;Mostafa, Ahmed
抗药性流感病毒的不断进化突出了将具有抗流感活性的天然来源的安全植物化学物质重新利用为新型广谱抗流感药物的必要性。在这项研究中，含氮生物碱的病毒抑制活性进行了测试，对流感病毒A/H1N1和A/H5 N1。测试的生物碱对MDCK的细胞毒性显示出高安全性范围（CC 50> 200 μg/ml），允许筛选其抗流感潜力。 在此，硫酸阿托品、盐酸毛果芸香碱和秋水仙碱显示出抗H5 N1活性，IC 50值分别为2.300、0.210和0.111 µg/ml。通过检测三种高效生物碱对季节性甲型H1N1流感病毒的有效IC 50值，进一步描述了IC 50值的验证，结果显示IC 50值相当，分别为0.204、0.637和0.326 µg/ml。进一步的研究表明，秋水仙碱可以抑制病毒感染，主要是通过干扰IAV复制和抑制病毒吸附，而硫酸阿托品和盐酸毛果芸香碱可以直接影响病毒的无细胞杀病毒作用。有趣的是，在计算机分子对接研究表明，阿托品，毛果芸香碱，秋水仙碱的能力，正确结合内的神经氨酸酶的活性位点的流感病毒A/H1N1和A/H5 N1。这三种生物碱具有良好的结合能以及优良的结合模式，类似于共结晶配体。另一方面，与体外结果一致，只有秋水仙碱可以正确结合甲型流感病毒（IAV）的M2质子通道。这可能解释了秋水仙素在病毒复制周期的复制阶段的体外抗病毒活性。这项研究强调了包括秋水仙碱在内的生物活性生物碱的抗流感功效。因此，这些生物碱应在体内（临床前和临床研究）进一步表征，以开发为抗IAV药物。
The continuous evolution of drug-resistant influenza viruses highlights the necessity for repurposing naturally-derived and safe phytochemicals with anti-influenza activity as novel broad-spectrum anti-influenza medications. In this study, nitrogenous alkaloids were tested for their viral inhibitory activity against influenza A/H1N1 and A/H5N1 viruses. The cytotoxicity of tested alkaloids on MDCK showed a high safety range (CC50 > 200 µg/ml), permitting the screening for their anti-influenza potential. Herein, atropine sulphate, pilocarpine hydrochloride and colchicine displayed anti-H5N1 activities with IC50 values of 2.300, 0.210 and 0.111 µg/ml, respectively. Validation of the IC50 values was further depicted by testing the three highly effective alkaloids, based on their potent IC50 values against seasonal influenza A/H1N1 virus, showing comparable IC50 values of 0.204, 0.637 and 0.326 µg/ml, respectively. Further investigation suggests that colchicine could suppress viral infection by primarily interfering with IAV replication and inhibiting viral adsorption, while atropine sulphate and pilocarpine hydrochloride could directly affect the virus in a cell-free virucidal effect. Interestingly, the in silico molecular docking studies suggest the abilities of atropine, pilocarpine, and colchicine to bind correctly inside the active sites of the neuraminidases of both influenza A/H1N1 and A/H5N1 viruses. The three alkaloids exhibited good binding energies as well as excellent binding modes that were similar to the co-crystallized ligands. On the other hand, consistent with in vitro results, only colchicine could bind correctly against the M2-proton channel of influenza A viruses (IAVs). This might explicate the in vitro antiviral activity of colchicine at the replication stage of the virus replication cycle. This study highlighted the anti-influenza efficacy of biologically active alkaloids including colchicine. Therefore, these alkaloids should be further characterized in vivo (preclinical and clinical studies) to be developed as anti-IAV agents.
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影响因子：
168.9
作者：
Gubareva, LV;Kaiser, L;Hayden, FG
通讯作者：
Hayden, FG
DOI：
10.1128/aem.16.4.588-594.1968
发表时间：
1968-01-01
期刊：
APPLIED MICROBIOLOGY
影响因子：
--
作者：
GAUSH, CR;SMITH, TF
通讯作者：
SMITH, TF
影响因子：
5.1
作者：
Eissa, Ibrahim H.;Dahab, Mohammed A.;Beauchemin, Andre M.
通讯作者：
Beauchemin, Andre M.
影响因子：
3.2
作者：
El-Shesheny, Rabeh;Bagato, Ola;Kayali, Ghazi
通讯作者：
Kayali, Ghazi
影响因子：
2.7
作者：
Cetina-Montejo, Lisseth;Ayora-Talavera, Guadalupe;Borges-Argaez, Rocio
通讯作者：
Borges-Argaez, Rocio