FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
This manuscript (1) reports on extensive and compelling experimental evidence and translational data from retrospective review of clinical registries, which show that pharmacological inhibition of the farnesoid X receptor (FXR) could be a novel intervention for the prevention or treatment of COVID-19. The in vitro and in vivo studies show that FXR antagonism reduces ACE2 expression, which subsequently reduces SARS-CoV-2 infection in the lung, liver and gastrointestinal tract.
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Brevini T, Maes M, Webb GJ, John BV, Fuchs CD, Buescher G, Wang L, Griffiths C, Brown ML, Scott WE 3rd, Pereyra-Gerber P, Gelson WTH, Brown S, Dillon S, Muraro D, Sharp J, Neary M, Box H, Tatham L, Stewart J, Curley P, Pertinez H, Forrest S, Mlcochova P, Varankar SS, Darvish-Damavandi M, Mulcahy VL, Kuc RE, Williams TL, Heslop JA, Rossetti D, Tysoe OC, Galanakis V, Vila-Gonzalez M, Crozier TWM, Bargehr J, Sinha S, Upponi SS, Fear C, Swift L, Saeb-Parsy K, Davies SE, Wester A, Hagström H, Melum E, Clements D, Humphreys P, Herriott J, Kijak E, Cox H, Bramwell C, Valentijn A, Illingworth CJR; UK-PBC research consortium, Dahman B, Bastaich DR, Ferreira RD, Marjot T, Barnes E, Moon AM, Barritt AS 4th, Gupta RK, Baker S, Davenport AP, Corbett G, Gorgoulis VG, Buczacki SJA, Lee JH, Matheson NJ, Trauner M, Fisher AJ, Gibbs P, Butler AJ, Watson CJE, Mells GF, Dougan G, Owen A, Lohse AW, Vallier L, Sampaziotis F. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature. 2022 Dec 5. doi: 10.1038/s41586-022-05594-0. Epub ahead of print. PMID: 36470304.
Comments by the Guide to Pharmacology Curation Team, University of Edinburgh
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