Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An acute respiratory disorder (COVID-19) that accelerated across the globe has been found to be caused by a novel strain of coronaviruses (SARS-CoV-2). The absence of a specific antiviral drug or vaccination has promoted the development of immediate therapeutic responses against SARS-CoV-2. As increased levels of plasma chemokines and, cytokines and an uncontrolled influx of inflammatory cells were observed in lethal cases, it was concluded that the severity of the infection corresponded with the imbalanced host immunity against the virus. Tracing back the knowledge acquired from SERS and MERS infections, clinical evidence suggested similar host immune reactions and host ACE2 receptor-derived invasion by SARS-CoV-2. Further studies revealed the integral role of proteases (TMPRSS2, cathepsins, plasmin, etc.) in viral entry and the immune system. This review aims to provide a brief review on the latest research progress in identifying the potential role of proteases in SARS-CoV-2 viral spread and infection and combines it with already known information on the role of different proteases in providing an immune response. It further proposes a multidisciplinary clinical approach to target proteases specifically, through a combinatorial administration of protease inhibitors. This predictive review may help in providing a perspective to gain deeper insights of the proteolytic web involved in SARS-CoV-2 viral invasion and host immune response.
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PMID:COVID-19: Targeting Proteases in Viral Invasion and Host Immune Response. 3319

The high mortality of specific groups from COVID-19 highlights the importance of host-viral interactions and the potential benefits from enhancing host defenses. SARS-CoV-2 requires angiotensin converting enzyme (ACE)2 as a receptor for cell entry and infection. While both ACE inhibitors and spironolactone can upregulate tissue ACE2, there are important points of discrimination between these approaches. The virus requires proteolytic processing of its spike protein by transmembrane protease receptor serine type 2 (TMPRSS2) to enable binding to cellular ACE2. Since TMPRSS2 contains an androgen promoter, it may be downregulated by the antiandrogenic actions of spironolactone. Furin and plasmin also process the spike protein. They are inhibited by protease nexin 1 or serine E2 (PN1) that is upregulated by angiotensin II but downregulated by aldosterone. Therefore, spironolactone should selectively downregulate furin and plasmin. Furin also promotes pulmonary edema while plasmin promotes hemovascular dysfunction. Thus, a downregulation of furin and plasmin by PN1 could be a further benefit of MRAs beyond their well established organ protection. We review the evidence that spironolactone may be the preferred RASSi to increase PN1 and decrease TMPRSS2, furin and plasmin activities and thereby to reduce viral cell binding, entry, infectivity and bad outcomes. This hypothesis requires direct investigation.
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PMID:Is spironolactone the preferred renin-angiotensin-aldosterone inhibitor for protection against COVID-19? 3327 89