Hegazy Akram, Mostafa Islam, Elshaier Yaseen A M M, Mahmoud Sara H, Abo Shama Noura M, Shehata Mahmoud, Yahya Galal, Nasr Nasr Fawzy, El-Halawany Ali M, Ali Mohamed Abdelalim, Ali Mohamed A, Mraheil Mobarak Abu, El-Shazly Assem M, Mostafa Ahmed
Department of Agricultural Microbiology, Faculty of Agriculture, Cairo University, Giza District, 12613Giza, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig44519, Egypt.
ACS Omega. 2022 Nov 2;7(45):41212-41223. doi: 10.1021/acsomega.2c04867. eCollection 2022 Nov 15.
The evolution of drug-resistant viral strains following natural acquisition of resistance mutations is a major obstacle to antiviral therapy. Besides the improper prescription of the currently licensed anti-influenza medications, M2-blockers and neuraminidase inhibitors, to control poultry outbreaks/infections potentiates the emergence of drug-resistant influenza variants. Therefore, there is always a necessity to find out new alternatives with potent activity and high safety. Plant extracts and plant-based chemicals represent a historical antiviral resource with remarkable safety and to control the emerging and remerging health threats caused by viral infections. Herein, a panel of purified plant extracts and subsequent plant-derived chemicals were evaluated for their anti-avian influenza activity against zoonotic highly pathogenic influenza A/H5N1 virus. Interestingly, santonica flower extract () showed the most promising anti-H5N1 activity with a highly safe half-maximal cytotoxic concentration 50 (CC > 10 mg/mL) and inhibitory concentration 50 (IC of 3.42 μg/mL). To confirm the anti-influenza activity, we assessed the anti-influenza activity of the selected plant extracts against seasonal human influenza A/H1N1 virus and we found that santonica flower extract showed a robust anti-influenza activity that was comparable to the activity against influenza A/H5N1. Furthermore, the mode of action for santonica flower extract with strong inhibitory activity on the abovementioned influenza strains was elucidated, showing a virucidal effect. To go deeper about the activity of the chemometric component of the extract, the major constituent, santonin, was further selected for screening against influenza A/H5N1 (IC = 1.701 μg/mL) and influenza A/H1N1 (IC = 2.91 μg/mL). The oxygen of carbonyl functionality in the cyclohexene ring succeeded to form a hydrogen bond with the neuraminidase active site. Despite the fact that santonin revealed similarity to both reference neuraminidase inhibitors in forming hydrogen bonds with essential amino acids, it illustrated shape alignment to oseltamivir more than zanamivir according to Tanimoto algorithms. This study highlights the applicability of santonica flower extract as a promising natural antiviral against low and highly pathogenic influenza A viruses.
自然获得耐药性突变后耐药病毒株的进化是抗病毒治疗的主要障碍。除了目前已获许可的抗流感药物（M2阻滞剂和神经氨酸酶抑制剂）处方不当外，用于控制家禽疫情/感染会促使耐药流感变种的出现。因此，始终有必要寻找具有强效活性和高安全性的新替代物。植物提取物和植物源化学物质是一种具有卓越安全性的历史悠久的抗病毒资源，可用于控制由病毒感染引起的新出现和再次出现的健康威胁。在此，对一组纯化的植物提取物及其后的植物源化学物质针对人兽共患高致病性甲型H5N1流感病毒的抗禽流感活性进行了评估。有趣的是，山道年花提取物表现出最有前景的抗H5N1活性，其半数最大细胞毒性浓度（CC50）极高（CC50>10mg/mL），半数抑制浓度（IC50）为3.42μg/mL。为了确认抗流感活性，我们评估了所选植物提取物对季节性人类甲型H1N1流感病毒的抗流感活性，发现山道年花提取物表现出强大的抗流感活性，与抗甲型H5N1流感的活性相当。此外，阐明了对上述流感毒株具有强抑制活性的山道年花提取物的作用模式，显示出杀病毒作用。为了更深入了解提取物化学计量成分的活性，进一步选择了主要成分山道年针对甲型H5N1流感（IC50=1.701μg/mL）和甲型H1N1流感（IC50=2.91μg/mL）进行筛选。环己烯环中羰基官能团的氧成功地与神经氨酸酶活性位点形成了氢键。尽管山道年在与必需氨基酸形成氢键方面显示出与两种参考神经氨酸酶抑制剂相似，但根据谷本算法，它与奥司他韦的形状比对更甚于扎那米韦。本研究突出了山道年花提取物作为一种有前景的天然抗病毒药物对抗低致病性和高致病性甲型流感病毒的适用性。
