一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Scientific Reports >>article
Scientific Reports

Scientific Reports

IF: 3.8
Download PDF

Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells

Published:2 November 2022 DOI: 10.1038/s41598-022-21034-5 PMID: 36323770
Xammy Huu Wrynla,?Eddie Wehri,?Erik Van Dis,?Scott B Biering,?Livia H Yamashiro,?Chi Zhu,?Julien Stroumza,?Claire Dugast-Darzacq,?Thomas G W Graham,?Xuanting Wang,?Steffen Jockusch,?Chuanjuan Tao,?Minchen Chien,?Wei Xie,?Dinshaw J Patel,?Cindy Meyer,?Aitor Garzia,?Thomas Tuschl,?James J Russo,?Jingyue Ju,?Anders M N??r,?Sarah Stanley,?Julia Schaletzky

Abstract

SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy is only moderate, and improved treatment strategies are urgently needed. To accomplish this goal, we devised a strategy to identify compounds that act synergistically with remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput screening in the presence of submaximal remdesivir concentrations, using a human lung epithelial cell line infected with a clinical isolate of SARS-CoV-2. This identified 20 approved drugs that act synergistically with remdesivir, many with favorable pharmacokinetic and safety profiles. Strongest effects were observed with established antivirals, Hepatitis C virus nonstructural protein 5A (HCV NS5A) inhibitors velpatasvir and elbasvir. Combination with their partner drugs sofosbuvir and grazoprevir further increased efficacy, increasing remdesivir's apparent potency?>?25-fold. We report that HCV NS5A inhibitors act on the SARS-CoV-2 exonuclease proofreader, providing a possible explanation for the synergy observed with nucleoside analog remdesivir. FDA-approved Hepatitis C therapeutics Epclusa? (velpatasvir/sofosbuvir) and Zepatier? (elbasvir/grazoprevir) could be further optimized to achieve potency and pharmacokinetic properties that support clinical evaluation?in combination with?remdesivir.

Substances (7)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
Remdesivir 1809249-37-3 C27H35N6O8P 366 suppliers $10.00-$13340.00
Remdesivir 1809249-37-3 C27H35N6O8P 366 suppliers $10.00-$13340.00
Remdesivir 1809249-37-3 C27H35N6O8P 366 suppliers $10.00-$13340.00
Remdesivir 1809249-37-3 C27H35N6O8P 366 suppliers $10.00-$13340.00
GS 5734 1809249-37-3 C27H35N6O8P - Inquiry
GS 5734 1809249-37-3 C27H35N6O8P - Inquiry

Similar articles

IF:19.8

Generation of iPSC-derived human venous endothelial cells for the modeling of vascular malformations and drug discovery

Cell stem cell Zihang Pan, Qiyang Yao,etc Published: 22 November 2024
IF:19.3

Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery.

Pharmacological Reviews Tobias Atkin, Stefano Comai,etc Published: 1 April 2018
东丰县| 潞城市| 思南县| 平武县| 竹溪县| 庆安县| 五台县| 台湾省| 南江县| 乌什县| 乐亭县| 五原县| 廊坊市| 巴林右旗| 明溪县| 西乌珠穆沁旗| 信宜市| 利川市| 通辽市| 信丰县| 武功县| 阿瓦提县| 都匀市| 张家口市| 河源市| 金阳县| 富阳市| 临桂县| 托克托县| 万载县| 开化县| 栖霞市| 广水市| 双峰县| 抚松县| 台中县| 额尔古纳市| 吴忠市| 霞浦县| 叙永县| 阿城市|