Many individuals infected with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) develop no or only mild symptoms, but some can go on onto develop a spectrum of pathologies including pneumonia, acute respiratory distress syndrome, respiratory failure, systemic inflammation, and multiorgan failure. Many pathogens, viral and non-viral, can elicit these pathologies, which justifies reconsidering whether the target of therapeutic approaches to fight pathogen infections should be (a) the pathogen itself, (b) the pathologies elicited by the pathogen interaction with the human host, or (c) a combination of both. While little is known about the immunopathology of SARS-CoV-2, it is well-established that the above-mentioned pathologies are associated with hyper-inflammation, tissue damage, and the perturbation of target organ metabolism. Mounting evidence has shown that these processes are regulated by endoproteinases (particularly, matrix metalloproteinases (MMPs)). Here, we review what is known about the roles played by MMPs in the development of COVID-19 and postulate a mechanism by which MMPs could influence energy metabolism in target organs, such as the lung. Finally, we discuss the suitability of MMPs as therapeutic targets to increase the metabolic tolerance of the host to damage inflicted by the pathogen infection, with a focus on SARS-CoV-2.
【저자키워드】 COVID-19, SARS-CoV-2, Inflammation, metabolism, MMP, pathogen, metabolic tolerance, AMPK, 【초록키워드】 pathology, Respiratory failure, acute respiratory distress syndrome, Pneumonia, Infection, lung, immunopathology, severe acute respiratory syndrome Coronavirus, metabolism, Severe acute respiratory syndrome, Viral, pathogen, metabolic tolerance, energy metabolism, hyper-inflammation, target, Pathogens, systemic inflammation, matrix metalloproteinases, respiratory, Spectrum, Pathologies, mechanism, mild symptoms, therapeutic targets, acute respiratory distress, Coronavirus-2, Evidence, Combination, Interaction, Therapeutic approach, Perturbation, therapeutic target, focus, respiratory distress, target organs, matrix metalloproteinase, acute respiratory syndrome, target organ, acute respiratory syndrome coronavirus, tissue damage, therapeutic approaches, damage, individual, acute respiratory syndrome coronavirus-2, multiorgan failure, syndrome, human host, organs, organ, while, Host, shown, develop, elicit, regulated, elicited, Mounting, 【제목키워드】 metabolic tolerance, metabolic, targeting, increase,