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 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.