| Id |
Subject |
Object |
Predicate |
Lexical cue |
| TextSentencer_T1 |
0-149 |
Sentence |
denotes |
Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model. |
| TextSentencer_T2 |
150-161 |
Sentence |
denotes |
BACKGROUND: |
| TextSentencer_T3 |
162-259 |
Sentence |
denotes |
Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. |
| TextSentencer_T4 |
260-445 |
Sentence |
denotes |
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). |
| TextSentencer_T5 |
446-603 |
Sentence |
denotes |
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. |
| TextSentencer_T6 |
604-612 |
Sentence |
denotes |
METHODS: |
| TextSentencer_T7 |
613-698 |
Sentence |
denotes |
A 2019-nCoV related pangolin coronavirus GX_P2V/pangolin/2017/ Guangxi was described. |
| TextSentencer_T8 |
699-863 |
Sentence |
denotes |
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. |
| TextSentencer_T9 |
864-965 |
Sentence |
denotes |
The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. |
| TextSentencer_T10 |
966-1113 |
Sentence |
denotes |
Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2X infection. |
| TextSentencer_T11 |
1114-1209 |
Sentence |
denotes |
The antiviral activities and antiviral mechanisms of potential drugs were further investigated. |
| TextSentencer_T12 |
1210-1365 |
Sentence |
denotes |
Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. |
| TextSentencer_T13 |
1366-1374 |
Sentence |
denotes |
RESULTS: |
| TextSentencer_T14 |
1375-1555 |
Sentence |
denotes |
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. |
| TextSentencer_T15 |
1556-1710 |
Sentence |
denotes |
Three drugs-cepharanthine (CEP), selamectin and mefloquine hydrochloride exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. |
| TextSentencer_T16 |
1711-1845 |
Sentence |
denotes |
CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 μmol/L. |
| TextSentencer_T17 |
1846-2049 |
Sentence |
denotes |
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.). |
| TextSentencer_T18 |
2050-2146 |
Sentence |
denotes |
Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. |
| TextSentencer_T19 |
2147-2359 |
Sentence |
denotes |
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). |
| TextSentencer_T20 |
2360-2372 |
Sentence |
denotes |
CONCLUSIONS: |
| TextSentencer_T21 |
2373-2448 |
Sentence |
denotes |
Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. |
| TextSentencer_T22 |
2449-2547 |
Sentence |
denotes |
CEP, selamectin and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. |
| TextSentencer_T23 |
2548-2715 |
Sentence |
denotes |
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. |
