Chen, Yanwen;Lear, Travis B.;Evankovich, John W.;Larsen, Mads B.;Lin, Bo;Alfaras, Irene;Kennerdell, Jason R.;Salminen, Laura;Camarco, Daniel P.;Lockwood, Karina C.;Tuncer, Ferhan;Liu, Jie;Myerburg, Michael M.;McDyer, John F.;Liu, Yuan;Finkel, Toren;Chen, Bill B. published 《A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry》 in 2021. The article was appeared in 《Nature Communications》. They have made some progress in their research.Category: chiral-phosphine-ligands The article mentions the following:
Abstract: SARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small mols. that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clin. trial compounds We identify homoharringtonine and halofuginone as the most attractive agents, reducing endogenous TMPRSS2 expression at sub-micromolar concentrations These effects appear to be mediated by a drug-induced alteration in TMPRSS2 protein stability. We further demonstrate that halofuginone modulates TMPRSS2 levels through proteasomal-mediated degradation that involves the E3 ubiquitin ligase component DDB1- and CUL4-associated factor 1 (DCAF1). Finally, cells exposed to homoharringtonine and halofuginone, at concentrations of drug known to be achievable in human plasma, demonstrate marked resistance to SARS-CoV-2 infection in both live and pseudoviral in vitro models. Given the safety and pharmacokinetic data already available for the compounds identified in our screen, these results should help expedite the rational design of human clin. trials designed to combat active COVID-19 infection. The experimental procedure involved many compounds, such as ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) .
((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a potent inhibitor of selenoenzyme thioredoxin reductase (TrxR), which is involved in defense against oxidative stress.Category: chiral-phosphine-ligands
Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis