Involvement of Matrix Metalloproteinases in COVID-19: Molecular Targets, Mechanisms, and Insights for Therapeutic Interventions

Biology (Basel). 2023 Jun 10;12(6):843. doi: 10.3390/biology12060843.

Abstract

MMPs are enzymes involved in SARS-CoV-2 pathogenesis. Notably, the proteolytic activation of MMPs can occur through angiotensin II, immune cells, cytokines, and pro-oxidant agents. However, comprehensive information regarding the impact of MMPs in the different physiological systems with disease progression is not fully understood. In the current study, we review the recent biological advances in understanding the function of MMPs and examine time-course changes in MMPs during COVID-19. In addition, we explore the interplay between pre-existing comorbidities, disease severity, and MMPs. The reviewed studies showed increases in different MMP classes in the cerebrospinal fluid, lung, myocardium, peripheral blood cells, serum, and plasma in patients with COVID-19 compared to non-infected individuals. Individuals with arthritis, obesity, diabetes, hypertension, autoimmune diseases, and cancer had higher MMP levels when infected. Furthermore, this up-regulation may be associated with disease severity and the hospitalization period. Clarifying the molecular pathways and specific mechanisms that mediate MMP activity is important in developing optimized interventions to improve health and clinical outcomes during COVID-19. Furthermore, better knowledge of MMPs will likely provide possible pharmacological and non-pharmacological interventions. This relevant topic might add new concepts and implications for public health in the near future.

Keywords: SARS-CoV-2; biomarker; diseases; extracellular compartment; inflammation; metallopeptidases.

Grants and funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. The authors are also grateful for the financial support provided by the Decanato de Pesquisa e Inovação e de Pós-Graduação (grant nos. DPI/DPG N.° 01/2022). Fundação de Apoio a Pesquisa do Distrito Federal (FAPDF) (grant number 00193.00000773/2021-72, 00193.00000859/2021-3; 00193.00001222/2021-26; 00193-00002357/2022-90), and the National Council for Scientific and Technological Development (CNPq; process numbers 309435/2020-0 and 310269/2021). The authors are also grateful for the financial support provided by the Decanato de Pós-Graduação (grant DPG N.° 0007/2022).