Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment.
Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment.
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DOI：
10.1016/j.isci.2021.102367
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发表时间：
2021-04-23
期刊：
影响因子：
5.8
通讯作者：
Wakita T
中科院分区：
文献类型：
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作者：
Ohashi H;Watashi K;Saso W;Shionoya K;Iwanami S;Hirokawa T;Shirai T;Kanaya S;Ito Y;Kim KS;Nomura T;Suzuki T;Nishioka K;Ando S;Ejima K;Koizumi Y;Tanaka T;Aoki S;Kuramochi K;Suzuki T;Hashiguchi T;Maenaka K;Matano T;Muramatsu M;Saijo M;Aihara K;Iwami S;Takeda M;McKeating JA;Wakita T
迫切需要针对2019年冠状病毒病的抗病毒治疗。我们在严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的细胞培养模型中筛选了一组已获批准的药物，并在VeroE6/TMPRSS2细胞中发现了两种比候选药物雷米西韦和氯喹具有更高抗病毒潜力的新药物：抗炎药物头孢拉辛和人类免疫缺陷病毒蛋白酶抑制剂奈非那韦。Cepharanthine通过阻断病毒与靶细胞的结合来抑制SARS-CoV-2的入侵，而奈非那韦则部分通过抑制蛋白酶来抑制病毒复制。根据它们不同的作用模式，强调了这种联合治疗在限制SARS-CoV-2增殖方面的协同作用。体外抗病毒活性的数学建模与计算的肺内总药物浓度相结合预测，奈非那韦将把病毒清除的时间缩短4.9天，而头孢嘌呤/奈非那韦的联合使用提高了他们的预期疗效。这些结果为进一步评价头孢花碱和奈非那韦的潜在抗SARS-CoV-2活性奠定了基础。奈非那韦(NFV)抑制SARS-CoV-2复制头孢拉坦(CEP)抑制SARS-CoV-2与靶细胞的黏附NFV与CEP联合可协同增强抗病毒活性NFV与CEP在临床剂量下可缩短病毒消除时间医药；药物制剂；病毒学；
Antiviral treatments targeting the coronavirus disease 2019 are urgently required. We screened a panel of already approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new agents having higher antiviral potentials than the drug candidates such as remdesivir and chroloquine in VeroE6/TMPRSS2 cells: the anti-inflammatory drug cepharanthine and human immunodeficiency virus protease inhibitor nelfinavir. Cepharanthine inhibited SARS-CoV-2 entry through the blocking of viral binding to target cells, while nelfinavir suppressed viral replication partly by protease inhibition. Consistent with their different modes of action, synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation was highlighted. Mathematical modeling in vitro antiviral activity coupled with the calculated total drug concentrations in the lung predicts that nelfinavir will shorten the period until viral clearance by 4.9 days and the combining cepharanthine/nelfinavir enhanced their predicted efficacy. These results warrant further evaluation of the potential anti-SARS-CoV-2 activity of cepharanthine and nelfinavir. Nelfinavir (NFV) inhibits SARS-CoV-2 replication Cepharanthine (CEP) inhibits SARS-CoV-2 attachment to target cells Combination of NFV and CEP can synergistically augment antiviral activity NFV and CEP are estimated to shorten the time to viral elimination at clinical doses Medical Substance; Pharmaceutical Preparation; Virology;