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普利替德辛,一种细胞延伸因子eEF1a的抑制剂,以及莫努匹拉韦,一种核糖核苷胞苷类似物,两种对严重急性呼吸综合征冠状病毒2具有强效活性的新型化合物

[Plitidepsin, an inhibitor of the cell elongation factor eEF1a, and molnupiravir an analogue of the ribonucleoside cytidine, two new chemical compounds with intense activity against SARS-CoV-2].

作者信息

Reina J

机构信息

Jordi Reina, Unidad de Virología, Hospital Universitario Son Espases. Facultad de Medicina UIB. Carretera de Valldemossa 79, 07120 Palma de Mallorca. Spain.

出版信息

Rev Esp Quimioter. 2021 Oct;34(5):402-407. doi: 10.37201/req/042.2021. Epub 2021 Apr 27.

DOI:10.37201/req/042.2021
PMID:33902254
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8638831/
Abstract

The knowledge of the replicative cycle of SARS-CoV-2 and its interactions with cellular proteins has opened a new therapeutic possibility based on blocking those essential for the virus. The cellular protein elongation factor eEF1A could be a good target. Among its natural inhibitors are didemnins and their related chemical compounds such as plitidepsin. In human cell culture, this compound is capable of inhibiting the virus with a potency 27,5 times that of remdesivir. It must be administered intravenously. Of the ribonucleoside analogues, molnupiravir (MK-4483/EIDD-2801) (hydroxy-cytidine) determines a lethal mutagenesis on SARS-CoV-2. In animals, after oral administration, the pulmonary viral load decreases 25,000 times and when administered as prophylaxis, approximately 100,000 times. It prevents the transmission of the virus and eliminates its presence in the oropharynx. Both chemicals have started Phase I / II human clinical trials.

摘要

对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)复制周期及其与细胞蛋白相互作用的了解,开启了基于阻断病毒必需蛋白的新治疗可能性。细胞蛋白延伸因子eEF1A可能是一个良好的靶点。其天然抑制剂包括didemnins及其相关化合物,如plitidepsin。在人类细胞培养中,该化合物抑制病毒的效力是瑞德西韦的27.5倍。它必须通过静脉注射给药。在核糖核苷类似物中,莫努匹拉韦(MK-4483/EIDD-2801)(羟基胞苷)可导致SARS-CoV-2发生致死性诱变。在动物中,口服给药后,肺部病毒载量降低25000倍,预防性给药时降低约100000倍。它可防止病毒传播并消除其在口咽中的存在。这两种化学物质均已开始I/II期人体临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed6/8638831/5bde6c698915/revespquimioter-34-402-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed6/8638831/4aa1fc3b1b4b/revespquimioter-34-402-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed6/8638831/c6f108efd5ff/revespquimioter-34-402-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed6/8638831/508c0f906d96/revespquimioter-34-402-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed6/8638831/5bde6c698915/revespquimioter-34-402-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed6/8638831/4aa1fc3b1b4b/revespquimioter-34-402-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed6/8638831/c6f108efd5ff/revespquimioter-34-402-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed6/8638831/508c0f906d96/revespquimioter-34-402-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ed6/8638831/5bde6c698915/revespquimioter-34-402-g004.jpg

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Nature. 2021 Mar;591(7850):451-457. doi: 10.1038/s41586-021-03312-w. Epub 2021 Feb 9.
2
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Science. 2021 Feb 26;371(6532):926-931. doi: 10.1126/science.abf4058. Epub 2021 Jan 25.
3
Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting.
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Bioinformation. 2021 Nov 30;17(11):932-939. doi: 10.6026/97320630017932. eCollection 2021.
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