Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV
Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV
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DOI：
10.1038/s41467-019-13940-6
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发表时间：
2020-01-10
影响因子：
16.6
通讯作者：
Baric, Ralph S.
中科院分区：
文献类型：
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作者：
Sheahan, Timothy P.;Sims, Amy C.;Baric, Ralph S.
中东呼吸综合征冠状病毒 (MERS-CoV) 是一种严重呼吸道疾病的病原体，自 2012 年以来，已在 27 个国家造成超过 2468 例人类感染和超过 851 例死亡。尽管目前正在中东王国对洛匹那韦、利托那韦和干扰素 β (LPV/RTV-IFNb) 的组合疗法进行人体评估，但目前尚无批准的治疗中东呼吸综合征冠状病毒 (MERS-CoV) 的治疗方法。 沙特阿拉伯。在这里，我们证明瑞德西韦 (RDV) 和 IFNb 在体外具有优于 LPV 和 RTV 的抗病毒活性。在小鼠中，预防性和治疗性 RDV 均可改善肺功能，减少肺部病毒载量和严重的肺部病理。相比之下，预防性 LPV/RTV-IFNb 会略微降低病毒载量，而不影响其他疾病参数。治疗性 LPV/RTV-IFNb 可改善肺功能，但不会减少病毒复制或严重肺部病理。因此，我们提供了 RDV 治疗 MERS-CoV 感染潜力的体内证据。
Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.