Targeting Host Cell Proteases to Prevent SARS-CoV-2 Invasion

被引:28
作者
Kaur, Upinder [1 ]
Chakrabarti, Sankha Shubhra [2 ]
Ojha, Bisweswar [3 ]
Pathak, Bhairav Kumar [4 ]
Singh, Amit [3 ]
Saso, Luciano [3 ]
Chakrabarti, Sasanka [3 ]
机构
[1] Banaras Hindu Univ, Inst Med Sci, Dept Pharmacol, Varanasi, Uttar Pradesh, India
[2] Banaras Hindu Univ, Inst Med Sci, Dept Geriatr Med, Varanasi, Uttar Pradesh, India
[3] Sapienza Univ Rome, Dept Physiol & Pharmacol, Rome, India
[4] Maharishi Markandeshwar Deemed Univ, MM Inst Med Sci & Res, Dept Biochem & Cent Res Cell, Ambala, Haryana, India
关键词
COVID-19; TMPRSS; cathepsin; furin; plasmin; chloroquine; TRYPSIN-INHIBITOR; INFLUENZA-VIRUS; CORONAVIRUS; TMPRSS2; SERINE; CLEAVAGE; TROPISM;
D O I
10.2174/1389450121666200924113243
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) has spread worldwide and caused widespread devastation. In the absence of definitive therapy, symptomatic management remains the standard of care. Repurposing of many existing drugs, including several anti-viral drugs, is being attempted to tackle the COVID-19 pandemic. However, most of them have failed to show significant benefit in clinical trials. An attractive approach may be to target host proteases involved in SARS-CoV-2 pathogenesis. The priming of the spike (S) protein of the virus by proteolytic cleavage by the transmembrane serine protease-2 (TMPRSS2) is necessary for the fusion of the virus to the host cell after it binds to its receptor angiotensin converting enzyme-2 (ACE2). There are other proteases with varying spatiotemporal locations that may be important for viral entry and subsequent replication inside the cells, and these include trypsin, furin and cathepsins. In this report, we have discussed the tentative therapeutic role of inhibitors of TMPRSS2, cathepsin, trypsin, furin, plasmin, factor X and elastase in infection caused by SARS-CoV-2. Both available evidence, as well as hypotheses, are discussed, with emphasis on drugs which are approved for other indications such as bromhexine, ammonium chloride, nafamostat, camostat, tranexamic acid, epsilon amino-caproic acid, chloroquine, ulinastatin, aprotinin and anticoagulant drugs. Simultaneously, novel compounds being tested and problems with using these agents are also discussed.
引用
收藏
页码:192 / 201
页数:10
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