Antiviral Activity of Micafungin and Its Derivatives against SARS-CoV-2 RNA Replication.
Antiviral Activity of Micafungin and Its Derivatives against SARS-CoV-2 RNA Replication.
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DOI：
10.3390/v15020452
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发表时间：
2023-02-06
期刊：
影响因子：
--
通讯作者：
Watashi K
中科院分区：
文献类型：
--
作者：
Nakajima S;Ohashi H;Akazawa D;Torii S;Suzuki R;Fukuhara T;Watashi K
棘白菌素类抗真菌药物，包括米卡芬净、阿尼芬净和卡泊芬净，最近已报道对各种病毒如黄病毒、甲病毒和冠状病毒表现出抗病毒作用。本研究以米卡芬净及其衍生物为研究对象，分析了它们对严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的抗病毒活性。米卡芬净衍生物Mi-2和Mi-5显示出比米卡芬净更高的抗病毒活性，在VeroE 6/TMPRSS 2细胞中，50%最大抑制浓度（IC 50）分别为5.25和6.51 µM（比米卡芬净强3.8至4.7倍），50%细胞毒性浓度（CC 50）>64 µM。这种高抗SARS-CoV-2活性在人肺上皮细胞衍生的Calu-3细胞中也是保守的。米卡芬净、Mi-2和Mi-5可抑制细胞内病毒复制过程;此外，这些化合物对SARS-CoV-2变异体具有活性，包括Delta（AY.122，hCoV-19/日本/TY 11 -927/2021），Omicron（BA.1.18，hCoV-19/Japan/TY 38 -873/2021），一种对瑞德西韦耐药的变体（R10/E796 G C799 F）和对casirivimab/imdevimab抗体混合物（E406 W）具有抗性的变体;因此，我们的结果为米卡芬净衍生物用于开发抗病毒剂的潜在用途提供了基本证据。
Echinocandin antifungal drugs, including micafungin, anidulafungin, and caspofungin, have been recently reported to exhibit antiviral effects against various viruses such as flavivirus, alphavirus, and coronavirus. In this study, we focused on micafungin and its derivatives and analyzed their antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The micafungin derivatives Mi-2 and Mi-5 showed higher antiviral activity than micafungin, with 50% maximal inhibitory concentration (IC50) of 5.25 and 6.51 µM, respectively (3.8 to 4.7-fold stronger than micafungin) and 50% cytotoxic concentration (CC50) of >64 µM in VeroE6/TMPRSS2 cells. This high anti-SARS-CoV-2 activity was also conserved in human lung epithelial cell-derived Calu-3 cells. Micafungin, Mi-2, and Mi-5 were suggested to inhibit the intracellular virus replication process; additionally, these compounds were active against SARS-CoV-2 variants, including Delta (AY.122, hCoV-19/Japan/TY11-927/2021), Omicron (BA.1.18, hCoV-19/Japan/TY38-873/2021), a variant resistant to remdesivir (R10/E796G C799F), and a variant resistant to casirivimab/imdevimab antibody cocktail (E406W); thus, our results provide basic evidence for the potential use of micafungin derivatives for developing antiviral agents.
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