Il n’existe actuellement aucun traitement de la forme aiguë de la COVID-19, la maladie causée par l’infection par le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2). These compounds are promising candidates for further investigation against SARS-CoV-2.
Acs citation for chemdoodle pro#
This work has identified several phenothiazines with limited neurotransmitter receptor and transporter interactions and that may provide the dual action of inhibiting SARS-CoV-2 M pro to prevent viral replication and promote the release of anti-inflammatory cytokines to curb viral-induced inflammation. Docking results were compared with remdesivir and showed similar interactions with key residues Glu-166 and Gln-189 in the active site. The compounds with limited interactions with neurotransmitter receptors and transporters showed micromolar (µM) K i values. Nine phenothiazines showed inhibition constants <10 µM. All compounds were found to bind to the active site of SARS-CoV-2 M pro and showed K i values ranging from 1.30 to 52.4 µM in a rigid active site. Because most side-effects of phenothiazines are due to interactions with various neurotransmitter receptors and transporters, phenothiazines with few such interactions were also investigated. Nineteen phenothiazine drugs were investigated using in silico modelling techniques to predict binding energies and inhibition constants ( K i values) with SARS-CoV-2 M pro.
The phenothiazine moiety has demonstrated drug versatility for biological systems, including inhibition of butyrylcholinesterase, a property important in the cholinesterase anti-inflammatory cascade. The main protease (M pro) of SARS-CoV-2 is an essential enzyme for viral replication and an attractive target for disease intervention. COVID-19, caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2), currently has no treatment for acute infection.
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