Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids

被引：14

作者：

Rahmani, Waleed ^{[1
,2
]}

Chung, Hyunjae ^{[2
]}

Sinha, Sarthak ^{[3
]}

Bui-Marinos, Maxwell P. ^{[2
,4
,5
]}

Arora, Rohit ^{[3
]}

Jaffer, Arzina ^{[3
]}

Corcoran, Jennifer A. ^{[2
,4
,5
]}

Biernaskie, Jeff ^{[3
,6
,7
]}

Chun, Justin ^{[1
,2
]}

机构：

[1] Univ Calgary, Hlth Res Innovat Ctr 4A12, Cumming Sch Med, Dept Med, 3280 Hosp Dr NW, Calgary, AB T2N 4Z6, Canada

[2] Univ Calgary, Cumming Sch Med, Calvin Phoebe & Joan Snyder Inst Chron Dis, Calgary, AB, Canada

[3] Univ Calgary, Fac Vet Med, Dept Comparat Biol & Expt Med, Heritage Med Res Bldg,Room 402,3300 Hosp Dr NW, Calgary, AB T2N 4N1, Canada

[4] Univ Calgary, Microbiol Immunol & Infect Dis Dept, Calgary, AB, Canada

[5] Univ Calgary, Charbonneau Canc Res Inst, Calgary, AB, Canada

[6] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada

[7] Univ Calgary, Alberta Childrens Hosp Res Inst, Calgary, AB, Canada

来源：

ISCIENCE | 2022年 / 25卷 / 02期

关键词：

RESPIRATORY SYNDROME CORONAVIRUS; RENIN-ANGIOTENSIN SYSTEM; CONVERTING ENZYME-INHIBITION; II RECEPTOR BLOCKERS; SPIKE PROTEIN; CELL ENTRY; FUNCTIONAL RECEPTOR; ACE2; COVID-19; TROPISM;

D O I：

10.1016/j.isci.2022.103818

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

COVID-19-associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. The susceptibility of human kidneys to direct SARS-CoV-2 infection and modulation of the renin-angiotensin II signaling (RAS) pathway by viral infection remain poorly characterized. Using induced pluripotent stem cell-derived kidney organoids, SARS-CoV-1, SARSCoV-2, and MERS-CoV tropism, defined by the paired expression of a host receptor (ACE2 , NRP1 or DPP4) and protease (TMPRSS2 , TMPRSS4 , FURIN , CTSB or CTSL), was identified primarily among proximal tubule cells. Losartan, an angiotensin II receptor blocker being tested in patients with COVID-19, inhibited angiotensin II-mediated internalization of ACE2, upregulated interferon -stimulated genes (IFITM1 and BST2) known to restrict viral entry, and attenuated the infection of proximal tubule cells by SARS-CoV-2. Our work highlights the susceptibility of proximal tubule cells to SARS-CoV-2 and reveals a putative protective role for RAS inhibitors during SARS-CoV-2 infection.

引用

页数：25

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