Can dapagliflozin have a protective effect against COVID-19 infection? A hypothesis.

It has been reported that frequent occurrence of COVID-19 infection in these patients is associated with low cytosolic pH. During virus infection, serum lactate dehydrogenase (LDH) level excessively rises. LDH is a cytosolic enzyme and the serum level increases as the cell break down. When anaerobic conditions develop, lactate formation increases from pyruvate. Cell pH is regulated by very complex mechanisms. When lactate increases in the extracellular area, this symporter carries lactate and H ion into the cell, and the intracellular pH quickly becomes acidic. Paradoxically, Na/H exchanger activation takes place. While H ion is thrown out of the cell, Na and Ca enter the cell. When Na and Ca increase in the cell, the cells swell and die. Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor. Dapagliflozin has been reported to reduce lactate levels by various mechanisms. Also, it reduces oxygen consumption in tissues and causes the use of glucose in the aerobic pathway, thereby reducing lactate production. A lactate decrease in the environment reduces the activation of lactate/H symporter. Thus, the H ion pumping into the cell by this symporter is reduced and the cytosolic pH is maintained. Dapagliflozin also directly inhibits NHE. Thus, Na and Ca flow to the cell are inhibited. Dapagliflozin provides the continuation of the structure and functions of the cells. Dapagliflozin can prevent the severe course of COVID-19 infection by preventing the lowering of cytosolic pH and reducing the viral load.