Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2.
Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2.
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DOI：
10.3389/fimmu.2020.586572
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发表时间：
2020
影响因子：
7.3
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Xiao X;Wang C;Chang D;Wang Y;Dong X;Jiao T;Zhao Z;Ren L;Dela Cruz CS;Sharma L;Lei X;Wang J
COVID-19大流行已感染数百万人，死亡率超过100万。迫切需要找到可以帮助清除病毒的治疗剂，以防止严重疾病和死亡。确定有效和更安全的药物可以为单独或联合治疗COVID-19感染提供更多选择。在这里，我们对大约1，700种美国FDA批准的化合物进行了高通量筛选，以确定可以有效抑制包括SARS-CoV-2在内的冠状病毒复制的新型治疗药物。我们的两步筛选首先使用人类冠状病毒株OC 43来鉴定具有抗冠状病毒活性的化合物。然后筛选有效化合物，以确定其抑制SARS-CoV-2的有效性。这些筛选鉴定了20种抗SARS-CoV-2药物，包括先前报道的化合物，如羟氯喹、阿苯磺酸、盐酸阿比朵尔、盐酸替洛龙、盐酸决奈达隆、甲氟喹和盐酸硫利达嗪。新鉴定的药物中有5种的安全指数（细胞毒性/有效浓度）>600，表明与在类似实验中安全指数为22的羟氯喹相比，治疗窗较宽。机制上，发现五种有效化合物（盐酸芬地林、莫能菌素钠盐、沃替西汀、盐酸舍曲林和salifungin）阻断SARS-CoV-2 S蛋白介导的细胞融合。这些FDA批准的化合物可以提供我们在大流行期间迫切需要的治疗选择。
COVID-19 pandemic has infected millions of people with mortality exceeding >1 million. There is an urgent need to find therapeutic agents that can help clear the virus to prevent severe disease and death. Identifying effective and safer drugs can provide more options to treat COVID-19 infections either alone or in combination. Here, we performed a high throughput screening of approximately 1,700 US FDA-approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 20 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine besylate, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, mefloquine, and thioridazine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of >600, indicating a wide therapeutic window compared to hydroxychloroquine which had a safety index of 22 in similar experiments. Mechanistically, five of the effective compounds (fendiline HCl, monensin sodium salt, vortioxetine, sertraline HCl, and salifungin) were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA-approved compounds can provide much needed therapeutic options that we urgently need during the midst of the pandemic.
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影响因子：
9.8
作者：
Jack A;Ferro LS;Trnka MJ;Wehri E;Nadgir A;Nguyenla X;Fox D;Costa K;Stanley S;Schaletzky J;Yildiz A
通讯作者：
Yildiz A
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
2.3
作者：
Smetana Jr, Karel;Rosel, Daniel;BrAbek, Jan
通讯作者：
BrAbek, Jan
影响因子：
6.1
作者：
Kandeel, Mahmoud;Al-Nazawi, Mohammed
通讯作者：
Al-Nazawi, Mohammed
DOI：
10.1080/07391102.2020.1802346
发表时间：
2020-08-04
影响因子：
4.4
作者：
Gul, Seref;Ozcan, Onur;Kavakli, Ibrahim Halil
通讯作者：
Kavakli, Ibrahim Halil