Enteric symptomology seen in early-stage severe acute respiratory syndrome (SARS)-2003 and COVID-19 is evidence of virus replication occurring in the intestine, liver and pancreas. Aberrant lipid metabolism in morbidly obese individuals adversely affects the COVID-19 immune response and increases disease severity. Such observations are in line with the importance of lipid metabolism in COVID-19, and point to the gut as a site for intervention as well as a therapeutic target in treating the disease. Formation of complex lipid membranes and palmitoylation of coronavirus proteins are essential during viral replication and assembly. Inhibition of fatty acid synthase (FASN) and restoration of lipid catabolism by activation of AMP-activated protein kinase (AMPK) impede replication of coronaviruses closely related to SARS-coronavirus-2 (CoV-2). In vitro findings and clinical data reveal that the FASN inhibitor, orlistat, and the AMPK activator, metformin, may inhibit coronavirus replication and reduce systemic inflammation to restore immune homeostasis. Such observations, along with the known mechanisms of action for these types of drugs, suggest that targeting fatty acid lipid metabolism could directly inhibit virus replication while positively impacting the patient’s response to COVID-19.
【저자키워드】 Antiviral, Spike protein, membrane protein, endoplasmic reticulum stress response, unfolded protein response, mTORC1, SREBP-1, nonstructural protein, envelope protein, replicative organelle, 【초록키워드】 COVID-19, coronavirus, disease severity, drugs, Intervention, inhibition, Replication, metformin, Protein, Viral, AMPK, viral replication, intestine, Immune homeostasis, membrane, virus replication, systemic inflammation, respiratory, inhibitor, liver, mechanism, COVID-19 immune response, Fatty acid, assembly, pancreas, Evidence, Coronavirus replication, lipid metabolism, palmitoylation, Gut, therapeutic target, protein kinase, evidence of, orlistat, observation, acute respiratory syndrome, Activation, Clinical data, individual, complex, obese, restoration, FASN, Affect, enteric, coronavirus protein, inhibit, the disease, increase, reduce, Formation, fatty, morbidly obese, 【제목키워드】 COVID-19, Fatty acid, Lipid, lipid metabolism, acid, nexus,