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Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model.

Identifieur interne : 000174 ( PubMed/Corpus ); précédent : 000173; suivant : 000175

Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model.

Auteurs : Hua-Hao Fan ; Li-Qin Wang ; Wen-Li Liu ; Xiao-Ping An ; Zhen-Dong Liu ; Xiao-Qi He ; Li-Hua Song ; Yi-Gang Tong

Source :

RBID : pubmed:32149769

Abstract

Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those without such facilities or 2019-novel coronavirus (2019-nCoV). This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV related coronavirus model.

DOI: 10.1097/CM9.0000000000000797
PubMed: 32149769

Links to Exploration step

pubmed:32149769

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<name sortKey="Fan, Hua Hao" sort="Fan, Hua Hao" uniqKey="Fan H" first="Hua-Hao" last="Fan">Hua-Hao Fan</name>
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<nlm:affiliation>Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.</nlm:affiliation>
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<name sortKey="Wang, Li Qin" sort="Wang, Li Qin" uniqKey="Wang L" first="Li-Qin" last="Wang">Li-Qin Wang</name>
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<name sortKey="Liu, Wen Li" sort="Liu, Wen Li" uniqKey="Liu W" first="Wen-Li" last="Liu">Wen-Li Liu</name>
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<name sortKey="An, Xiao Ping" sort="An, Xiao Ping" uniqKey="An X" first="Xiao-Ping" last="An">Xiao-Ping An</name>
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<name sortKey="Liu, Zhen Dong" sort="Liu, Zhen Dong" uniqKey="Liu Z" first="Zhen-Dong" last="Liu">Zhen-Dong Liu</name>
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<name sortKey="He, Xiao Qi" sort="He, Xiao Qi" uniqKey="He X" first="Xiao-Qi" last="He">Xiao-Qi He</name>
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<name sortKey="Song, Li Hua" sort="Song, Li Hua" uniqKey="Song L" first="Li-Hua" last="Song">Li-Hua Song</name>
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<name sortKey="Tong, Yi Gang" sort="Tong, Yi Gang" uniqKey="Tong Y" first="Yi-Gang" last="Tong">Yi-Gang Tong</name>
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<nlm:affiliation>Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.</nlm:affiliation>
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<name sortKey="Wang, Li Qin" sort="Wang, Li Qin" uniqKey="Wang L" first="Li-Qin" last="Wang">Li-Qin Wang</name>
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<name sortKey="Liu, Wen Li" sort="Liu, Wen Li" uniqKey="Liu W" first="Wen-Li" last="Liu">Wen-Li Liu</name>
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<name sortKey="An, Xiao Ping" sort="An, Xiao Ping" uniqKey="An X" first="Xiao-Ping" last="An">Xiao-Ping An</name>
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<name sortKey="Liu, Zhen Dong" sort="Liu, Zhen Dong" uniqKey="Liu Z" first="Zhen-Dong" last="Liu">Zhen-Dong Liu</name>
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<name sortKey="He, Xiao Qi" sort="He, Xiao Qi" uniqKey="He X" first="Xiao-Qi" last="He">Xiao-Qi He</name>
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<name sortKey="Song, Li Hua" sort="Song, Li Hua" uniqKey="Song L" first="Li-Hua" last="Song">Li-Hua Song</name>
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<div type="abstract" xml:lang="en">Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those without such facilities or 2019-novel coronavirus (2019-nCoV). This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV related coronavirus model.</div>
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<Year>2020</Year>
<Month>03</Month>
<Day>09</Day>
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<Year>2020</Year>
<Month>Mar</Month>
<Day>06</Day>
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<Title>Chinese medical journal</Title>
<ISOAbbreviation>Chin. Med. J.</ISOAbbreviation>
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<ArticleTitle>Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model.</ArticleTitle>
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<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those without such facilities or 2019-novel coronavirus (2019-nCoV). This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV related coronavirus model.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">A 2019-nCoV related pangolin coronavirus GX_P2V/pangolin/2017/ Guangxi was described. Whether GX_P2X uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA) -mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2X infection. The antiviral activities and antiviral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs-cepharanthine (CEP), selamectin and mefloquine hydrochloride exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] × 10vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP has potent antiviral activities against both viral entry (1.00 ± 0.37 vs. 0.46 ± 0.12, t = 2.42, P < 0.05) and viral replication (1.00 ± 0.43 vs. [6.18 ± 0.95] × 10, t = 3.98, P < 0.05).</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and clinical trial of CEP for treatment of 2019-nCoV infection is warranted.</AbstractText>
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