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Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets.
mBio ( IF 6.4 ) Pub Date : 2020-05-22 , DOI: 10.1128/mbio.01114-20 Su-Jin Park 1, 2 , Kwang-Min Yu 1, 2 , Young-Il Kim 1, 2 , Se-Mi Kim 1, 2 , Eun-Ha Kim 1, 2 , Seong-Gyu Kim 1, 2 , Eun Ji Kim 1 , Mark Anthony B Casel 1, 2 , Rare Rollon 1 , Seung-Gyu Jang 1 , Min-Hyeok Lee 1 , Jae-Hyung Chang 1 , Min-Suk Song 1, 2 , Hye Won Jeong 3 , Younho Choi 4 , Weiqiang Chen 4 , Woo-Jin Shin 4 , Jae U Jung 5 , Young Ki Choi 2, 6
mBio ( IF 6.4 ) Pub Date : 2020-05-22 , DOI: 10.1128/mbio.01114-20 Su-Jin Park 1, 2 , Kwang-Min Yu 1, 2 , Young-Il Kim 1, 2 , Se-Mi Kim 1, 2 , Eun-Ha Kim 1, 2 , Seong-Gyu Kim 1, 2 , Eun Ji Kim 1 , Mark Anthony B Casel 1, 2 , Rare Rollon 1 , Seung-Gyu Jang 1 , Min-Hyeok Lee 1 , Jae-Hyung Chang 1 , Min-Suk Song 1, 2 , Hye Won Jeong 3 , Younho Choi 4 , Weiqiang Chen 4 , Woo-Jin Shin 4 , Jae U Jung 5 , Young Ki Choi 2, 6
Affiliation
Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.
中文翻译:
FDA 批准的药物对雪貂 SARS-CoV-2 感染的抗病毒功效。
由于迫切需要对 2019 年冠状病毒 (CoV) 病 (COVID-19) 患者进行治疗,因此在没有足够信息的情况下,已建议将一些 FDA 批准/重新利用的药物作为临床抗病毒候选药物。此外,关于抗病毒候选药物对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的有效性和安全性存在广泛争论,这表明需要快速的临床前动物研究来确定潜在的抗病毒候选药物进行人体试验。为此,在雪貂感染模型中评估了洛匹那韦-利托那韦、硫酸羟氯喹和恩曲他滨-替诺福韦对 SARS-CoV-2 感染的抗病毒功效。而洛匹那韦-利托那韦-、硫酸羟氯喹-、或恩曲他滨-替诺福韦治疗组的总体临床评分低于磷酸盐缓冲盐水 (PBS) 治疗的对照组,所有三个抗病毒候选药物治疗组的鼻洗液、粪便标本和呼吸道组织中的病毒滴度相似和PBS处理的对照组。只有恩曲他滨-替诺福韦治疗组在感染后 8 天 (dpi) 的鼻洗液中显示出比 PBS 治疗对照组更低的病毒滴度。为了进一步探索免疫抑制对病毒感染和临床结果的影响,用硫唑嘌呤(一种免疫抑制药物)治疗雪貂。与 PBS 处理的对照组相比,硫唑嘌呤免疫抑制的雪貂表现出更长的临床疾病期、更高的鼻甲病毒滴度、延迟的病毒清除、和显着降低血清中和 (SN) 抗体滴度。总之,所有测试的抗病毒药物都略微降低了受感染雪貂的总体临床评分,但没有显着影响体内病毒滴度。尽管动物和人类之间的药物功效存在潜在差异,但这些临床前雪貂数据应该对 COVID-19 患者的未来治疗提供高度信息。
更新日期:2020-06-30
中文翻译:
FDA 批准的药物对雪貂 SARS-CoV-2 感染的抗病毒功效。
由于迫切需要对 2019 年冠状病毒 (CoV) 病 (COVID-19) 患者进行治疗,因此在没有足够信息的情况下,已建议将一些 FDA 批准/重新利用的药物作为临床抗病毒候选药物。此外,关于抗病毒候选药物对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的有效性和安全性存在广泛争论,这表明需要快速的临床前动物研究来确定潜在的抗病毒候选药物进行人体试验。为此,在雪貂感染模型中评估了洛匹那韦-利托那韦、硫酸羟氯喹和恩曲他滨-替诺福韦对 SARS-CoV-2 感染的抗病毒功效。而洛匹那韦-利托那韦-、硫酸羟氯喹-、或恩曲他滨-替诺福韦治疗组的总体临床评分低于磷酸盐缓冲盐水 (PBS) 治疗的对照组,所有三个抗病毒候选药物治疗组的鼻洗液、粪便标本和呼吸道组织中的病毒滴度相似和PBS处理的对照组。只有恩曲他滨-替诺福韦治疗组在感染后 8 天 (dpi) 的鼻洗液中显示出比 PBS 治疗对照组更低的病毒滴度。为了进一步探索免疫抑制对病毒感染和临床结果的影响,用硫唑嘌呤(一种免疫抑制药物)治疗雪貂。与 PBS 处理的对照组相比,硫唑嘌呤免疫抑制的雪貂表现出更长的临床疾病期、更高的鼻甲病毒滴度、延迟的病毒清除、和显着降低血清中和 (SN) 抗体滴度。总之,所有测试的抗病毒药物都略微降低了受感染雪貂的总体临床评分,但没有显着影响体内病毒滴度。尽管动物和人类之间的药物功效存在潜在差异,但这些临床前雪貂数据应该对 COVID-19 患者的未来治疗提供高度信息。