PubMed_ArguminSci  

PubMed:32405156 JSONTXT 5 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function IAV-Glycan

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.