FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2.
FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2.
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FXR抑制作用可以通过减少ACE2来防止SARS-COV-2感染。
DOI：
10.1038/s41586-022-05594-0
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发表时间：
2023-03
期刊：
影响因子：
64.8
通讯作者：
Sampaziotis, Fotios
中科院分区：
文献类型：
--
作者：
Brevini, Teresa;Maes, Mailis;Webb, Gwilym J.;John, Binu, V;Fuchs, Claudia D.;Buescher, Gustav;Wang, Lu;Griffiths, Chelsea;Brown, Marnie L.;Scott, William E., III;Pereyra-Gerber, Pehuen;Gelson, William T. H.;Brown, Stephanie;Dillon, Scott;Muraro, Daniele;Sharp, Jo;Neary, Megan;Box, Helen;Tatham, Lee;Stewart, James;Curley, Paul;Pertinez, Henry;Forrest, Sally;Mlcochova, Petra;Varankar, Sagar S.;Darvish-Damavandi, Mahnaz;Mulcahy, Victoria L.;Kuc, Rhoda E.;Williams, Thomas L.;Heslop, James A.;Rossetti, Davide;Tysoe, Olivia C.;Galanakis, Vasileios;Vila-Gonzalez, Marta;Crozier, Thomas W. M.;Bargehr, Johannes;Sinha, Sanjay;Upponi, Sara S.;Fear, Corrina;Swift, Lisa;Saeb-Parsy, Kourosh;Davies, Susan E.;Wester, Axel;Hagstrom, Hannes;Melum, Espen;Clements, Darran;Humphreys, Peter;Herriott, Jo;Kijak, Edyta;Cox, Helen;Bramwell, Chloe;Valentijn, Anthony;Illingworth, Christopher J. R.;Dahman, Bassam;Bastaich, Dustin R.;Ferreira, Raphaella D.;Marjot, Thomas;Barnes, Eleanor;Moon, Andrew M.;Barritt, Alfred S.;Gupta, Ravindra K.;Baker, Stephen;Davenport, Anthony P.;Corbett, Gareth;Gorgoulis, Vassilis G.;Buczacki, Simon J. A.;Lee, Joo-Hyeon;Matheson, Nicholas J.;Trauner, Michael;Fisher, Andrew J.;Gibbs, Paul;Butler, Andrew J.;Watson, Christopher J. E.;Mells, George F.;Dougan, Gordon;Owen, Andrew;Lohse, Ansgar W.;Vallier, Ludovic;Sampaziotis, Fotios
通过调节病毒宿主受体（例如血管紧张素转换酶2（ACE2））来防止SARS-COV-2感染，可以代表一种新的Covid-19化学预防症方法，但是，控制ACE2的机制仍然不清楚ACE2的表达。 。然后，胃肠道和呼吸系统。小鼠和仓鼠。肝脏灌注的原位。这些发现在肝移植的受体的独立验证队列中，我们表明FXR在控制ACE2表达中起作用并提供证据该途径的调节可能有益于减少SARS-COV-2感染，为将来的临床试验铺平了道路。
FXR调节受covid-19的呼吸道和胃肠道系统组织中的ACE2水平，并用ursoxyoxycholic抑制FXR，可下调ACE2并降低对SARS-COV-COV-2感染的敏感性。
Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2), could represent a new chemoprophylactic approach for COVID-19 that complements vaccination. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials. FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.
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影响因子：
56.9
作者：
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者：
Clevers, Hans
DOI：
10.1183/13993003.02951-2021
发表时间：
2022-08
期刊：
The European respiratory journal
影响因子：
--
作者：
Evangelou K;Veroutis D;Paschalaki K;Foukas PG;Lagopati N;Dimitriou M;Papaspyropoulos A;Konda B;Hazapis O;Polyzou A;Havaki S;Kotsinas A;Kittas C;Tzioufas AG;de Leval L;Vassilakos D;Tsiodras S;Stripp BR;Papantonis A;Blandino G;Karakasiliotis I;Barnes PJ;Gorgoulis VG
通讯作者：
Gorgoulis VG
影响因子：
4.8
作者：
Balasubramaniyan, Natarajan;Luo, Yuhuan;Suchy, Frederick J.
通讯作者：
Suchy, Frederick J.
影响因子：
--
作者：
BJERKNES, M;CHENG, H
通讯作者：
CHENG, H
影响因子：
15.9
作者：
Jiang, Changtao;Xie, Cen;Gonzalez, Frank J.
通讯作者：
Gonzalez, Frank J.