PubMed:32405156
Annnotations
PubMed_ArguminSci
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T1 | 171-314 | DRI_Challenge | denotes | The emergence of SARS-coronavirus-2 (SARS-CoV-2) is responsible for a global pandemic disease referred to as coronavirus disease 19 (Covid-19). |
| T2 | 315-431 | DRI_Background | denotes | Hydroxychloroquine/azithromycin combination therapy is currently tested for curing Covid-19, with promising results. |
| T3 | 432-518 | DRI_Background | denotes | However, the molecular mechanism of action of this combination is not established yet. |
| T4 | 519-685 | DRI_Approach | denotes | Using molecular dynamics (MD) simulations we show that both drugs act in synergy to prevent any close contact between the virus and the plasma membrane of host cells. |
| T5 | 686-864 | DRI_Challenge | denotes | We reveal unexpected molecular similarity between azithromycin and the sugar moiety of GM1, a lipid raft ganglioside acting as a host attachment cofactor for respiratory viruses. |
| T6 | 865-973 | DRI_Background | denotes | Due to this mimicry, azithromycin interacts with the ganglioside-binding domain of SARS-CoV-2 spike protein. |
| T7 | 974-1119 | DRI_Background | denotes | This binding site shared by azithromycin and GM1 displays a conserved amino acid triad Q-134/F-135/N-137 located at the tip of the spike protein. |
| T8 | 1120-1277 | DRI_Outcome | denotes | We also show that hydroxychloroquine molecules can saturate virus attachment sites on gangliosides in the vicinity of the primary coronavirus receptor ACE-2. |
| T9 | 1278-1436 | DRI_Background | denotes | Taken together, these data show that azithromycin is directed against the virus, whereas hydroxychloroquine is directed against cellular attachment cofactors. |
| T10 | 1437-1546 | DRI_Outcome | denotes | We conclude that both drugs act as competitive inhibitors of SARS-CoV-2 attachment to the host cell membrane. |
| T11 | 1547-1701 | DRI_Outcome | denotes | This is consistent with a synergistic antiviral mechanism at the plasma membrane level, where the most efficient therapeutic intervention probably stands. |
| T12 | 1702-1843 | DRI_Outcome | denotes | This molecular mechanism may explain the beneficial effects of hydroxychloroquine/azithromycin combination therapy in patients with Covid-19. |
| T13 | 1844-1973 | DRI_Outcome | denotes | Incidentally, our data suggest that the conserved Q-134/F-135/N-137 triad could be considered as a target for vaccine strategies. |
LitCovid-OGER-BB
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T1 | 33-51 | CHEBI:5801;DG_20;CHEBI:5801 | denotes | hydroxychloroquine |
| T2 | 56-68 | CHEBI:2955;DG_6;CHEBI:2955 | denotes | azithromycin |
| T3 | 92-102 | SP_7 | denotes | SARS-CoV-2 |
| T4 | 139-144 | NCBITaxon:10239 | denotes | virus |
| T5 | 145-149 | GO:0018995 | denotes | host |
| T6 | 188-192 | SP_10 | denotes | SARS |
| T7 | 193-204 | NCBITaxon:11118 | denotes | coronavirus |
| T8 | 208-218 | SP_7 | denotes | SARS-CoV-2 |
| T9 | 280-291 | NCBITaxon:11118 | denotes | coronavirus |
| T10 | 304-312 | SP_7 | denotes | Covid-19 |
| T11 | 315-333 | CHEBI:5801;DG_20;CHEBI:5801 | denotes | Hydroxychloroquine |
| T12 | 334-346 | CHEBI:2955;DG_6;CHEBI:2955 | denotes | azithromycin |
| T13 | 398-406 | SP_7 | denotes | Covid-19 |
| T14 | 579-584 | CHEBI:23888;CHEBI:23888 | denotes | drugs |
| T15 | 641-646 | NCBITaxon:10239 | denotes | virus |
| T16 | 655-670 | GO:0005886 | denotes | plasma membrane |
| T17 | 736-748 | CHEBI:2955;DG_6;CHEBI:2955 | denotes | azithromycin |
| T18 | 780-785 | CHEBI:18059;CHEBI:18059;GO:0045121 | denotes | lipid |
| T19 | 786-790 | GO:0045121 | denotes | raft |
| T20 | 791-802 | CHEBI:5386;CHEBI:5386 | denotes | ganglioside |
| T21 | 831-839 | CHEBI:23357;CHEBI:23357 | denotes | cofactor |
| T22 | 844-855 | GO:0045333 | denotes | respiratory |
| T23 | 856-863 | NCBITaxon:10239 | denotes | viruses |
| T24 | 886-898 | CHEBI:2955;DG_6;CHEBI:2955 | denotes | azithromycin |
| T25 | 918-929 | CHEBI:28892;CHEBI:28892 | denotes | ganglioside |
| T26 | 938-944 | SO:0000417 | denotes | domain |
| T27 | 948-958 | SP_7 | denotes | SARS-CoV-2 |
| T28 | 979-991 | SO:0000409 | denotes | binding site |
| T29 | 1002-1014 | CHEBI:2955;DG_6;CHEBI:2955 | denotes | azithromycin |
| T30 | 1138-1156 | CHEBI:5801;DG_20;CHEBI:5801 | denotes | hydroxychloroquine |
| T31 | 1157-1166 | CHEBI:36357;CHEBI:36357 | denotes | molecules |
| T32 | 1180-1185 | NCBITaxon:10239 | denotes | virus |
| T33 | 1186-1202 | SO:0000366 | denotes | attachment sites |
| T34 | 1206-1218 | CHEBI:5386;CHEBI:5386 | denotes | gangliosides |
| T35 | 1250-1261 | NCBITaxon:11118 | denotes | coronavirus |
| T36 | 1271-1276 | G_3;PG_10;PR:000003622 | denotes | ACE-2 |
| T37 | 1315-1327 | CHEBI:2955;DG_6;CHEBI:2955 | denotes | azithromycin |
| T38 | 1352-1357 | NCBITaxon:10239 | denotes | virus |
| T39 | 1367-1385 | CHEBI:5801;DG_20;CHEBI:5801 | denotes | hydroxychloroquine |
| T40 | 1426-1435 | CHEBI:23357;CHEBI:23357 | denotes | cofactors |
| T41 | 1459-1464 | CHEBI:23888;CHEBI:23888 | denotes | drugs |
| T42 | 1484-1494 | CHEBI:35222;CHEBI:35222 | denotes | inhibitors |
| T43 | 1498-1508 | SP_7 | denotes | SARS-CoV-2 |
| T44 | 1527-1545 | GO:0033644 | denotes | host cell membrane |
| T45 | 1612-1627 | GO:0005886 | denotes | plasma membrane |
| T46 | 1765-1783 | CHEBI:5801;DG_20;CHEBI:5801 | denotes | hydroxychloroquine |
| T47 | 1784-1796 | CHEBI:2955;DG_6;CHEBI:2955 | denotes | azithromycin |
| T48 | 1834-1842 | SP_7 | denotes | Covid-19 |