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of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model.\nBACKGROUND: 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.\nMETHODS: 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.\nRESULTS: 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 \u003c 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 \u003c 0.05) and viral replication (1.00 ± 0.43 vs. [6.18 ± 0.95] × 10, t = 3.98, P \u003c 0.05).\nCONCLUSIONS: 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."}

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of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model.\nBACKGROUND: 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.\nMETHODS: 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.\nRESULTS: 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 \u003c 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 \u003c 0.05) and viral replication (1.00 ± 0.43 vs. [6.18 ± 0.95] × 10, t = 3.98, P \u003c 0.05).\nCONCLUSIONS: 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."}

{"project":"LitCovid-ArguminSci","denotations":[{"id":"T1","span":{"begin":0,"end":149},"obj":"DRI_Background"},{"id":"T2","span":{"begin":150,"end":259},"obj":"DRI_Background"},{"id":"T3","span":{"begin":260,"end":445},"obj":"DRI_Background"},{"id":"T4","span":{"begin":446,"end":603},"obj":"DRI_Background"},{"id":"T5","span":{"begin":604,"end":698},"obj":"DRI_Background"},{"id":"T6","span":{"begin":699,"end":863},"obj":"DRI_Background"},{"id":"T7","span":{"begin":864,"end":965},"obj":"DRI_Challenge"},{"id":"T8","span":{"begin":966,"end":1113},"obj":"DRI_Background"},{"id":"T9","span":{"begin":1114,"end":1209},"obj":"DRI_Background"},{"id":"T10","span":{"begin":1210,"end":1365},"obj":"DRI_Background"},{"id":"T11","span":{"begin":1366,"end":1555},"obj":"DRI_Background"},{"id":"T12","span":{"begin":1556,"end":1710},"obj":"DRI_Background"},{"id":"T13","span":{"begin":1711,"end":1845},"obj":"DRI_Outcome"},{"id":"T14","span":{"begin":1846,"end":1974},"obj":"DRI_Approach"},{"id":"T15","span":{"begin":1981,"end":1982},"obj":"DRI_Approach"},{"id":"T16","span":{"begin":1983,"end":2049},"obj":"DRI_Approach"},{"id":"T17","span":{"begin":2050,"end":2146},"obj":"DRI_Background"},{"id":"T18","span":{"begin":2147,"end":2359},"obj":"DRI_Outcome"},{"id":"T19","span":{"begin":2360,"end":2448},"obj":"DRI_Outcome"},{"id":"T20","span":{"begin":2449,"end":2547},"obj":"DRI_Challenge"},{"id":"T21","span":{"begin":2548,"end":2715},"obj":"DRI_Outcome"}],"text":"Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model.\nBACKGROUND: 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.\nMETHODS: 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.\nRESULTS: 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 \u003c 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 \u003c 0.05) and viral replication (1.00 ± 0.43 vs. [6.18 ± 0.95] × 10, t = 3.98, P \u003c 0.05).\nCONCLUSIONS: 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."}

{"project":"LitCovid-OGER","denotations":[{"id":"T1","span":{"begin":269,"end":273},"obj":"CHEBI:23888"},{"id":"T2","span":{"begin":916,"end":920},"obj":"CHEBI:23888"},{"id":"T3","span":{"begin":1428,"end":1433},"obj":"CHEBI:46882"},{"id":"T4","span":{"begin":1434,"end":1438},"obj":"CHEBI:37527"},{"id":"T5","span":{"begin":1568,"end":1581},"obj":"CHEBI:3546"},{"id":"T6","span":{"begin":1604,"end":1628},"obj":"CHEBI:6719"},{"id":"T7","span":{"begin":2469,"end":2493},"obj":"CHEBI:6719"},{"id":"T8","span":{"begin":2605,"end":2614},"obj":"CHEBI:35222"},{"id":"T1","span":{"begin":1210,"end":1215},"obj":"GO:0019012"},{"id":"T2","span":{"begin":1850,"end":1855},"obj":"GO:0019012"},{"id":"T3","span":{"begin":2218,"end":2223},"obj":"GO:0019012"},{"id":"T4","span":{"begin":2284,"end":2289},"obj":"GO:0019012"},{"id":"T5","span":{"begin":2618,"end":2621},"obj":"GO:0022623"},{"id":"T1","span":{"begin":1309,"end":1323},"obj":"MOP:0000635"},{"id":"T1","span":{"begin":719,"end":750},"obj":"PR:000003622"},{"id":"T2","span":{"begin":752,"end":756},"obj":"PR:000003622;PR:Q6NKN9"},{"id":"T3","span":{"begin":858,"end":862},"obj":"PR:000003622;PR:Q6NKN9"},{"id":"T4","span":{"begin":1485,"end":1489},"obj":"PR:000022942"},{"id":"T5","span":{"begin":1500,"end":1504},"obj":"PR:000003622;PR:Q6NKN9"},{"id":"T6","span":{"begin":1913,"end":1917},"obj":"PR:000022679"},{"id":"T7","span":{"begin":2618,"end":2621},"obj":"PR:Q8UVK2"},{"id":"T1","span":{"begin":239,"end":242},"obj":"SO:0001853"},{"id":"T2","span":{"begin":805,"end":826},"obj":"SO:0000646"},{"id":"T3","span":{"begin":828,"end":833},"obj":"SO:0000646"},{"id":"T4","span":{"begin":845,"end":854},"obj":"SO:0000893;SO:0000625"},{"id":"T5","span":{"begin":2494,"end":2497},"obj":"SO:0001853"}],"namespaces":[{"prefix":"PR","uri":"http://purl.obolibrary.org/obo/PR_"},{"prefix":"UBERON","uri":"http://purl.obolibrary.org/obo/UBERON_"}],"text":"Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model.\nBACKGROUND: 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.\nMETHODS: 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.\nRESULTS: 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 \u003c 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 \u003c 0.05) and viral replication (1.00 ± 0.43 vs. [6.18 ± 0.95] × 10, t = 3.98, P \u003c 0.05).\nCONCLUSIONS: 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."}

{"project":"LitCovid-PubTatorCentral","denotations":[{"id":"T1","span":{"begin":58,"end":77},"obj":"Disease:MESH:D018352"},{"id":"T2","span":{"begin":526,"end":545},"obj":"Disease:MESH:D018352"},{"id":"T3","span":{"begin":950,"end":964},"obj":"Disease:MESH:D007239"},{"id":"T4","span":{"begin":1084,"end":1086},"obj":"CellLine:CVCL:4582"},{"id":"T5","span":{"begin":1103,"end":1112},"obj":"Disease:MESH:D007239"},{"id":"T6","span":{"begin":1525,"end":1534},"obj":"Disease:MESH:D007239"},{"id":"T7","span":{"begin":1765,"end":1774},"obj":"Disease:MESH:D007239"},{"id":"T8","span":{"begin":2032,"end":2041},"obj":"Disease:MESH:D007239"},{"id":"T9","span":{"begin":2532,"end":2546},"obj":"Disease:MESH:D007239"},{"id":"T10","span":{"begin":2687,"end":2701},"obj":"Disease:MESH:D007239"}],"text":"Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model.\nBACKGROUND: 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.\nMETHODS: 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.\nRESULTS: 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 \u003c 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 \u003c 0.05) and viral replication (1.00 ± 0.43 vs. [6.18 ± 0.95] × 10, t = 3.98, P \u003c 0.05).\nCONCLUSIONS: 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."}

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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.\nMETHODS: 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.\nRESULTS: 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 \u003c 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 \u003c 0.05) and viral replication (1.00 ± 0.43 vs. [6.18 ± 0.95] × 10, t = 3.98, P \u003c 0.05).\nCONCLUSIONS: 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."}

{"project":"LitCovid-PD-MONDO-v1","denotations":[{"id":"T1","span":{"begin":58,"end":82},"obj":"Disease"},{"id":"T2","span":{"begin":228,"end":238},"obj":"Disease"},{"id":"T3","span":{"begin":526,"end":550},"obj":"Disease"},{"id":"T4","span":{"begin":552,"end":560},"obj":"Disease"},{"id":"T5","span":{"begin":945,"end":964},"obj":"Disease"},{"id":"T6","span":{"begin":955,"end":964},"obj":"Disease"},{"id":"T7","span":{"begin":1103,"end":1112},"obj":"Disease"},{"id":"T8","span":{"begin":1235,"end":1245},"obj":"Disease"},{"id":"T9","span":{"begin":1525,"end":1534},"obj":"Disease"},{"id":"T10","span":{"begin":1583,"end":1586},"obj":"Disease"},{"id":"T11","span":{"begin":1711,"end":1714},"obj":"Disease"},{"id":"T12","span":{"begin":1765,"end":1774},"obj":"Disease"},{"id":"T13","span":{"begin":1898,"end":1901},"obj":"Disease"},{"id":"T14","span":{"begin":1946,"end":1949},"obj":"Disease"},{"id":"T15","span":{"begin":2032,"end":2041},"obj":"Disease"},{"id":"T16","span":{"begin":2130,"end":2133},"obj":"Disease"},{"id":"T17","span":{"begin":2169,"end":2172},"obj":"Disease"},{"id":"T18","span":{"begin":2449,"end":2452},"obj":"Disease"},{"id":"T19","span":{"begin":2527,"end":2546},"obj":"Disease"},{"id":"T20","span":{"begin":2537,"end":2546},"obj":"Disease"},{"id":"T21","span":{"begin":2582,"end":2585},"obj":"Disease"},{"id":"T22","span":{"begin":2661,"end":2664},"obj":"Disease"},{"id":"T23","span":{"begin":2682,"end":2701},"obj":"Disease"},{"id":"T24","span":{"begin":2692,"end":2701},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/MONDO_0009902"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/MONDO_0009902"},{"id":"A12","pred":"mondo_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A13","pred":"mondo_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/MONDO_0009902"},{"id":"A14","pred":"mondo_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/MONDO_0009902"},{"id":"A15","pred":"mondo_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A16","pred":"mondo_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/MONDO_0009902"},{"id":"A17","pred":"mondo_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/MONDO_0009902"},{"id":"A18","pred":"mondo_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/MONDO_0009902"},{"id":"A19","pred":"mondo_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A20","pred":"mondo_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A21","pred":"mondo_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/MONDO_0009902"},{"id":"A22","pred":"mondo_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/MONDO_0009902"},{"id":"A23","pred":"mondo_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A24","pred":"mondo_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"}],"text":"Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model.\nBACKGROUND: 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.\nMETHODS: 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.\nRESULTS: 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 \u003c 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 \u003c 0.05) and viral replication (1.00 ± 0.43 vs. [6.18 ± 0.95] × 10, t = 3.98, P \u003c 0.05).\nCONCLUSIONS: 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."}

{"project":"LitCovid-PD-FMA-UBERON-v1","denotations":[{"id":"T1","span":{"begin":765,"end":769},"obj":"Body_part"},{"id":"T2","span":{"begin":823,"end":826},"obj":"Body_part"},{"id":"T3","span":{"begin":1087,"end":1092},"obj":"Body_part"},{"id":"T4","span":{"begin":1385,"end":1392},"obj":"Body_part"},{"id":"T5","span":{"begin":1428,"end":1438},"obj":"Body_part"},{"id":"T6","span":{"begin":1684,"end":1688},"obj":"Body_part"},{"id":"T7","span":{"begin":1856,"end":1859},"obj":"Body_part"},{"id":"T8","span":{"begin":1869,"end":1874},"obj":"Body_part"},{"id":"T9","span":{"begin":1932,"end":1937},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"fma_id","subj":"T1","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A7","pred":"fma_id","subj":"T7","obj":"http://purl.org/sig/ont/fma/fma67095"},{"id":"A5","pred":"fma_id","subj":"T5","obj":"http://purl.org/sig/ont/fma/fma82739"},{"id":"A4","pred":"fma_id","subj":"T4","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A9","pred":"fma_id","subj":"T9","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A3","pred":"fma_id","subj":"T3","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A2","pred":"fma_id","subj":"T2","obj":"http://purl.org/sig/ont/fma/fma67095"},{"id":"A6","pred":"fma_id","subj":"T6","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A8","pred":"fma_id","subj":"T8","obj":"http://purl.org/sig/ont/fma/fma68646"}],"text":"Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model.\nBACKGROUND: 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.\nMETHODS: 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.\nRESULTS: 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 \u003c 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 \u003c 0.05) and viral replication (1.00 ± 0.43 vs. [6.18 ± 0.95] × 10, t = 3.98, P \u003c 0.05).\nCONCLUSIONS: 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."}