AMP kinase: A promising therapeutic drug target for post-COVID-19 complications

Abstract

The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in severe respiratory issues and persistent complications, particularly affecting glucose metabolism. Patients with or without pre-existing diabetes often experience worsened symptoms, highlighting the need for innovative therapeutic approaches. AMPK, a crucial regulator of cellular energy balance, plays a pivotal role in glucose metabolism, insulin sensitivity, and inflammatory responses. AMPK activation, through allosteric or kinase-dependent mechanisms, impacts cellular processes like glucose uptake, fatty acid oxidation, and autophagy. The tissue-specific distribution of AMPK emphasizes its role in maintaining metabolic homeostasis throughout the body. Intriguingly, SARS-CoV-2 infection inhibits AMPK, contributing to metabolic dysregulation and post-COVID-19 complications. AMPK activators like capsaicinoids, curcumin, phytoestrogens, cilostazol, and momordicosides have demonstrated the potential to regulate AMPK activity. Compounds from various sources improve fatty acid oxidation and insulin sensitivity, with metformin showing opposing effects on AMPK activation compared to the virus, suggesting potential therapeutic options. The diverse effects of AMPK activation extend to its role in countering viral infections, further highlighting its significance in COVID-19. This review explores AMPK activation mechanisms, its role in metabolic disorders, and the potential use of natural compounds to target AMPK for post-COVID-19 complications. Also, it aims to review the possible methods of activating AMPK to prevent post-COVID-19 diabetes and cardiovascular complications. It also explores the use of natural compounds for their therapeutic effects in targeting the AMPK pathways. Targeting AMPK activation emerges as a promising avenue to mitigate the long-term effects of COVID-19, offering hope for improved patient outcomes and a better quality of life.