Amino acid sensing pathway: A major check point in the pathogenesis of obesity and COVID‐19

Philips, Aradhana Mariam; Khan, Nooruddin

Obesity and obesogenic comorbidities have been associated with COVID‐19 susceptibility and mortality. However, the mechanism of such correlations requires an in‐depth understanding. Overnutrition/excess serum amino acid profile during obesity has been linked with inflammation and reprogramming of translational machinery through hyperactivation of amino acid sensor mammalian target of rapamycin (mTOR), which is exploited by SARS‐CoV‐2 for its replication. Conversely, we have shown that the activation of general control nonderepressible 2 (GCN2)‐dependent amino acid starvation sensing pathway suppresses intestinal inflammation by inhibiting the production of reactive oxygen species (ROS) and interleukin‐1 beta (IL‐1β). While activation of GCN2 has shown to mitigate susceptibility to dengue infection, GCN2 deficiency increases viremia and inflammation‐associated pathologies. These findings reveal that the amino acid sensing pathway plays a significant role in controlling inflammation and viral infections. The current fact is that obesity/excess amino acids/mTOR activation aggravates COVID‐19, and it might be possible that activation of amino acid starvation sensor GCN2 has an opposite effect. This article focuses on the amino acid sensing pathways through which host cells sense the availability of amino acids and reprogram the host translation machinery to mount an effective antiviral response. Besides, how SARS‐CoV‐2 hijack and exploit amino acid sensing pathway for its replication and pathogenesis is also discussed.