Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19
Since its first appearance in December 2019 in the Chinese province of Wuhan, COVID-19 has spread rapidly throughout the world and poses a serious threat to public health. Acute respiratory failure due to widespread lung inflammation progress to acute respiratory distress syndrome (ARDS) with an alt...
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doaj-e0e2c11e78924875bc428b03b1945f282020-11-25T03:49:37ZengElsevierMedicine in Drug Discovery2590-09862020-09-017100052Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19B. Solun, MD0Y. Shoenfeld, MD, FRCP, MaACR1Department of Internal Medicine D, Hasharon Hospital, Rabin Medical Center, Petah Tikva, affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Israel; Correspondence to: B. Solun Department of Internal Medicine D, Rabin Medical Center, Hasharon Hospital 7, Keren Kayemet St., Petah Tiqva, Israel.Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, affiliated to Tel-Aviv University, Israel Laboratory of the Mosaics of Autoimmunity, Sechenov First Moscow State Medical University of the Ministry of Health of, the Russian Federation; Correspondence to: Y. Shoenfeld Chaim Sheba Medical Center The Zabludowicz Center, for Autoimmune Diseases Tel Hashomer, 5265601, Israel.Since its first appearance in December 2019 in the Chinese province of Wuhan, COVID-19 has spread rapidly throughout the world and poses a serious threat to public health. Acute respiratory failure due to widespread lung inflammation progress to acute respiratory distress syndrome (ARDS) with an altered pulmonary and alveolar function that can lead to disability, prolong hospitalizations, and adverse outcomes.While there is no specific treatment for severe acute lung injury (ALI) and ARDS due to the COVID-19 and the management is mostly supportive, it is very important to better understand the pathophysiological processes activated by the inflammatory mediators such as cytokines and metalloproteinases with the aim of their subsequent inhibition in the course of the complex treatment.Herein, we will discuss the pathophysiological mechanisms of ALI/ARDS, with a focus on the pivotal role played by matrix metalloproteinases (MMP) and the kinin-kallikrein system (KKS), and the effects of the possible pharmacological interventions.Aprotinin is a nonspecific protease inhibitor especially of trypsin, chymotrypsin, plasmin, and kallikrein, and it is many years in clinical use. Aprotinin inhibits the release of pro-inflammatory cytokines and involved in the process of glycoprotein homeostasis. Experimental data support that the use of aprotinin to inhibit MMPs and KKS may be a new potential approach to the treatment of ALI / ARDS.http://www.sciencedirect.com/science/article/pii/S2590098620300397COVID-19acute lung injuryacute respiratory distress syndromemetalloproteinasescytokineskinin-kallikrein system |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
B. Solun, MD Y. Shoenfeld, MD, FRCP, MaACR |
spellingShingle |
B. Solun, MD Y. Shoenfeld, MD, FRCP, MaACR Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19 Medicine in Drug Discovery COVID-19 acute lung injury acute respiratory distress syndrome metalloproteinases cytokines kinin-kallikrein system |
author_facet |
B. Solun, MD Y. Shoenfeld, MD, FRCP, MaACR |
author_sort |
B. Solun, MD |
title |
Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19 |
title_short |
Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19 |
title_full |
Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19 |
title_fullStr |
Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19 |
title_full_unstemmed |
Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19 |
title_sort |
inhibition of metalloproteinases in therapy for severe lung injury due to covid-19 |
publisher |
Elsevier |
series |
Medicine in Drug Discovery |
issn |
2590-0986 |
publishDate |
2020-09-01 |
description |
Since its first appearance in December 2019 in the Chinese province of Wuhan, COVID-19 has spread rapidly throughout the world and poses a serious threat to public health. Acute respiratory failure due to widespread lung inflammation progress to acute respiratory distress syndrome (ARDS) with an altered pulmonary and alveolar function that can lead to disability, prolong hospitalizations, and adverse outcomes.While there is no specific treatment for severe acute lung injury (ALI) and ARDS due to the COVID-19 and the management is mostly supportive, it is very important to better understand the pathophysiological processes activated by the inflammatory mediators such as cytokines and metalloproteinases with the aim of their subsequent inhibition in the course of the complex treatment.Herein, we will discuss the pathophysiological mechanisms of ALI/ARDS, with a focus on the pivotal role played by matrix metalloproteinases (MMP) and the kinin-kallikrein system (KKS), and the effects of the possible pharmacological interventions.Aprotinin is a nonspecific protease inhibitor especially of trypsin, chymotrypsin, plasmin, and kallikrein, and it is many years in clinical use. Aprotinin inhibits the release of pro-inflammatory cytokines and involved in the process of glycoprotein homeostasis. Experimental data support that the use of aprotinin to inhibit MMPs and KKS may be a new potential approach to the treatment of ALI / ARDS. |
topic |
COVID-19 acute lung injury acute respiratory distress syndrome metalloproteinases cytokines kinin-kallikrein system |
url |
http://www.sciencedirect.com/science/article/pii/S2590098620300397 |
work_keys_str_mv |
AT bsolunmd inhibitionofmetalloproteinasesintherapyforseverelunginjuryduetocovid19 AT yshoenfeldmdfrcpmaacr inhibitionofmetalloproteinasesintherapyforseverelunginjuryduetocovid19 |
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