Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo.
Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo.
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食品和药物管理局批准的药物在体外和体内抗SARS-CoV-2的广泛抗冠状病毒活性。
DOI：
10.1128/jvi.01218-20
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发表时间：
2020-10-14
影响因子：
5.4
通讯作者：
Frieman MB
中科院分区：
文献类型：
--
作者：
Weston S;Coleman CM;Haupt R;Logue J;Matthews K;Li Y;Reyes HM;Weiss SR;Frieman MB
没有FDA批准的任何冠状病毒的抗病毒药物，包括SARS-CoV-2。许多可能具有抗病毒活性的药物已经被批准用于人类使用，因此有可能迅速被重新利用为抗病毒药物。在这里，我们提供了评估20种FDA批准的抗SARS-CoV-2药物的抗病毒活性的数据，这些药物也在体外抑制SARS-CoV和MERS-CoV。我们发现其中17个抑制SARS-CoV-2，表明它们可能具有泛抗冠状病毒活性。我们直接追踪了其中的7种，发现它们都能抑制传染性SARS-CoV-2的产生。此外，我们评估了氯喹和氯丙嗪在体内使用小鼠适应SARS-CoV。我们发现两种药物都不能抑制肺部病毒复制，但都可以预防临床疾病。严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）于2019年底在中国出现，并迅速引发大流行，于2020年8月录得超过2000万例COVID-19病例（https：//covid19.who.int/）。没有FDA批准的任何冠状病毒的抗病毒药物或疫苗，包括SARS-CoV-2。目前对COVID-19的治疗仅限于支持疗法和FDA批准的药物的标签外使用。迫切需要快速开发和人体测试潜在的抗病毒药物。许多药物已经被批准用于人类使用，随后，人们对其安全性和潜在副作用有了很好的了解，使其更容易快速进入COVID-19患者的临床研究。在这里，我们提供了20种FDA批准的抗SARS-CoV-2药物的抗病毒活性数据，这些药物也抑制SARS-CoV和中东呼吸综合征冠状病毒（MERS-CoV）。我们发现其中17种在非细胞毒性浓度下抑制SARS-CoV-2。我们直接跟踪了其中的7个，以证明所有这些都能够抑制传染性SARS-CoV-2的产生。此外，我们评估了其中的两种，氯喹和氯丙嗪，在体内使用小鼠适应的SARS冠状病毒模型，发现这两种药物保护小鼠免受临床疾病。目前还没有FDA批准的针对任何冠状病毒的抗病毒药物，包括SARS-CoV-2。许多可能具有抗病毒活性的药物已经被批准用于人类使用，因此有可能迅速被重新利用为抗病毒药物。在这里，我们提供了评估20种FDA批准的抗SARS-CoV-2药物的抗病毒活性的数据，这些药物也在体外抑制SARS-CoV和MERS-CoV。我们发现其中17个抑制SARS-CoV-2，表明它们可能具有泛抗冠状病毒活性。我们直接追踪了其中的7种，发现它们都能抑制传染性SARS-CoV-2的产生。此外，我们评估了氯喹和氯丙嗪在体内使用小鼠适应SARS-CoV。我们发现，这两种药物都不能抑制病毒在肺部的复制，但都能预防临床疾病。
There are no FDA-approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly repurposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV in vitro. We found that 17 of these inhibit SARS-CoV-2, suggesting that they may have pan-anti-coronaviral activity. We directly followed up seven of these and found that they all inhibit infectious-SARS-CoV-2 production. Moreover, we evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We found that neither drug inhibited viral replication in the lungs, but both protected against clinical disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and has rapidly caused a pandemic, with over 20 million recorded COVID-19 cases in August 2020 (https://covid19.who.int/). There are no FDA-approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA-approved drugs. Rapid development and human testing of potential antivirals is urgently needed. Numerous drugs are already approved for human use, and subsequently, there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that 17 of these inhibit SARS-CoV-2 at non-cytotoxic concentrations. We directly followed up seven of these to demonstrate that all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found that both drugs protect mice from clinical disease. IMPORTANCE There are no FDA-approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly repurposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV in vitro. We found that 17 of these inhibit SARS-CoV-2, suggesting that they may have pan-anti-coronaviral activity. We directly followed up seven of these and found that they all inhibit infectious-SARS-CoV-2 production. Moreover, we evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We found that neither drug inhibited viral replication in the lungs, but both protected against clinical disease.