Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, USA.
Cellulose & Paper Department, National Research Centre, 33 El-Bohouth St. former (El-Tahrir St.), Dokki, Giza P.O. 12622, Egypt.
Molecules. 2020 May 17;25(10):2343. doi: 10.3390/molecules25102343.
Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5'--fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. The study revealed that remdesivir exhibited an EC value of 0.07 µM against HCoV-229E with TC of > 2.00 µM against MRC-5 cells. Parent NRTIs were found to be inactive against (HCoV-229E) at tested concentrations. Among all the NRTIs and 5'--fatty acyl conjugates of NRTIs, 5'--tetradecanoyl ester conjugate of FTC showed modest activity with EC and TC values of 72.8 µM and 87.5 µM, respectively. These data can be used for the design of potential compounds against other coronaviruses.
瑞德西韦是一种核苷酸前药，目前正在进行广泛的临床试验，以治疗 COVID-19。该前药代谢为其活性三磷酸酯形式，并干扰 SARS-COV-2 的 RNA 依赖性 RNA 聚合酶的作用。在此，我们报告瑞德西韦对人类冠状病毒 229E（HCoV-229E）的抗病毒活性，与已知的抗 HIV 药物相比。这些药物包括替诺福韦（TFV）、4'-乙炔基-2-氟-2'-脱氧腺苷（EFdA）、阿洛福韦（FLT）、拉米夫定（3TC）和恩曲他滨（FTC），它们是核苷逆转录酶抑制剂（NRTIs），以及一些 5'--脂肪酰化的抗 HIV 核苷缀合物。抗 HIV 核苷干扰 HIV RNA 依赖性 DNA 聚合酶和/或作为链终止子。正常的人成纤维细胞肺细胞（MRC-5）用于确定化合物的细胞毒性。研究表明，瑞德西韦对 HCoV-229E 的 EC 值为 0.07 µM，对 MRC-5 细胞的 TC 值大于 2.00 µM。在测试浓度下，亲代 NRTIs 对（HCoV-229E）没有活性。在所有 NRTIs 和 NRTIs 的 5'--脂肪酰缀合物中，FTC 的 5'--十四烷酰酯缀合物显示出适度的活性，EC 和 TC 值分别为 72.8 µM 和 87.5 µM。这些数据可用于设计针对其他冠状病毒的潜在化合物。
