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氟喹诺酮类抗生素对 SARS-CoV-2 和 MERS-CoV 表现出低抗病毒活性。

Fluoroquinolone Antibiotics Exhibit Low Antiviral Activity against SARS-CoV-2 and MERS-CoV.

机构信息

Biology of Vector-Borne Viruses Section, Laboratory of Virology, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.

Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

出版信息

Viruses. 2020 Dec 23;13(1):8. doi: 10.3390/v13010008.

Abstract

Repurposing FDA-approved drugs that treat respiratory infections caused by coronaviruses, such as SARS-CoV-2 and MERS-CoV, could quickly provide much needed antiviral therapies. In the current study, the potency and cellular toxicity of four fluoroquinolones (enoxacin, ciprofloxacin, levofloxacin, and moxifloxacin) were assessed in Vero cells and A549 cells engineered to overexpress ACE2, the SARS-CoV-2 entry receptor. All four fluoroquinolones suppressed SARS-CoV-2 replication at high micromolar concentrations in both cell types, with enoxacin demonstrating the lowest effective concentration 50 value (EC) of 126.4 μM in Vero cells. Enoxacin also suppressed the replication of MERS-CoV-2 in Vero cells at high micromolar concentrations. Cellular toxicity of levofloxacin was not found in either cell type. In Vero cells, minimal toxicity was observed following treatment with ≥37.5 μM enoxacin and 600 μM ciprofloxacin. Toxicity in both cell types was detected after moxifloxacin treatment of ≥300 μM. In summary, these results suggest that the ability of fluoroquinolones to suppress SARS-CoV-2 and MERS-CoV replication in cultured cells is limited.

摘要

重新利用治疗冠状病毒引起的呼吸道感染的已获 FDA 批准的药物,例如 SARS-CoV-2 和 MERS-CoV,可以快速提供急需的抗病毒疗法。在本研究中,评估了四种氟喹诺酮类药物(依诺沙星、环丙沙星、左氧氟沙星和莫西沙星)在过表达 SARS-CoV-2 进入受体 ACE2 的 Vero 细胞和 A549 细胞中的效力和细胞毒性。所有四种氟喹诺酮类药物在两种细胞类型中均以高微摩尔浓度抑制 SARS-CoV-2 的复制,依诺沙星在 Vero 细胞中显示出最低的有效浓度 50 值(EC)为 126.4 μM。依诺沙星还抑制了 MERS-CoV-2 在 Vero 细胞中的复制,浓度高达微摩尔。在两种细胞类型中均未发现左氧氟沙星的细胞毒性。在 Vero 细胞中,在用≥37.5 μM 依诺沙星和 600 μM 环丙沙星处理后,观察到最小的毒性。在两种细胞类型中,在用莫西沙星处理≥300 μM 后均检测到毒性。总之,这些结果表明氟喹诺酮类药物抑制 SARS-CoV-2 和 MERS-CoV 在培养细胞中的复制能力有限。

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