Aprotinin Inhibits SARS-CoV-2 Replication

被引：54

作者：

Bojkova, Denisa ^{[1
]}

Bechtel, Marco ^{[1
]}

McLaughlin, Katie-May ^{[2
]}

McGreig, Jake E. ^{[2
]}

Klann, Kevin ^{[3
]}

Bellinghausen, Carla ^{[4
]}

Rohde, Gernot ^{[4
]}

Jonigk, Danny ^{[5
,6
]}

Braubach, Peter ^{[5
,6
]}

Ciesek, Sandra ^{[1
,7
,8
]}

Muench, Christian ^{[3
,9
,10
]}

Wass, Mark N. ^{[2
]}

Michaelis, Martin ^{[2
]}

Cinatl, Jindrich ^{[1
]}

机构：

[1] Goethe Univ, Univ Hosp, Inst Med Virol, D-60596 Frankfurt, Germany

[2] Univ Kent, Sch Biosci, Canterbury CT2 7NJ, Kent, England

[3] Goethe Univ, Inst Biochem 2, Fac Med, D-60590 Frankfurt, Germany

[4] Goethe Univ, Univ Hosp, Dept Resp Med & Allergol, D-60590 Frankfurt, Germany

[5] Hannover Med Sch MHH, Inst Pathol, D-30625 Hannover, Germany

[6] Hannover Med Sch MHH, Biomed Res Endstage & Obstruct Lung Dis Hannover, German Ctr Lung Res, D-30625 Hannover, Germany

[7] DZIF, German Ctr Infect Res, External Partner Site, D-60596 Frankfurt, Germany

[8] Fraunhofer Inst Mol Biol & Appl Ecol IME, Branch Translat Med & Pharmacol, D-60596 Frankfurt, Germany

[9] Goethe Univ, Frankfurt Canc Inst, D-60596 Frankfurt, Germany

[10] Goethe Univ, Cardiopulm Inst, D-60590 Frankfurt, Germany

来源：

CELLS | 2020年 / 9卷 / 11期

关键词：

severe acute respiratory syndrome coronavirus; severe acute respiratory syndrome coronavirus 2; 2019-nCoV; COVID-19; antiviral; drug discovery; aprotinin; TRANEXAMIC ACID; IN-VITRO; VIRUS; TMPRSS2; CELLS;

D O I：

10.3390/cells9112377

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is the cause of the current coronavirus disease 19 (COVID-19) pandemic. Protease inhibitors are under consideration as virus entry inhibitors that prevent the cleavage of the coronavirus spike (S) protein by cellular proteases. Herein, we showed that the protease inhibitor aprotinin (but not the protease inhibitor SERPINA1/alpha-1 antitrypsin) inhibited SARS-CoV-2 replication in therapeutically achievable concentrations. An analysis of proteomics and translatome data indicated that SARS-CoV-2 replication is associated with a downregulation of host cell protease inhibitors. Hence, aprotinin may compensate for downregulated host cell proteases during later virus replication cycles. Aprotinin displayed anti-SARS-CoV-2 activity in different cell types (Caco2, Calu-3, and primary bronchial epithelial cell air-liquid interface cultures) and against four virus isolates. In conclusion, therapeutic aprotinin concentrations exert anti-SARS-CoV-2 activity. An approved aprotinin aerosol may have potential for the early local control of SARS-CoV-2 replication and the prevention of COVID-19 progression to a severe, systemic disease.

引用

页数：13

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