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  Indian J Med Microbiol
 

Figure 1: Pathogenesis of SARS-CoV-2 in COVID-19.The S1 subunit of spike S protein on the virus surface engages with membrane-bound cellular receptor carboxypeptidase ACE2 present over the cell membrane of lung epithelial cells (pulmonary alveolar type II cells), and S2 subunit stalk helps in cell fusion. TMPRSS2 protease aids in the attachment of ACE2 with virus S protein. After entry inside the cell, the virus replicates and destroys ACE2. The decrease in ACE2 (transmembranous and circulatory) perpetuates the RAAS pathway. Increase in angiotensin II levels in COVID-19 causes widespread injury by activation of ATR1 receptors. Activation of ATR1 causes vasoconstriction, inflammation, endothelial dysfunction, acute lung injury and myocardial injury. The physiological function of ACE2 is to degrade angiotensin II to angiotensin 1-7, and angiotensin I to angiotensin 1-9. Angiotensin 1-7 acts on MasR receptors on cell membranes, and has vasodilatory and antifibrotic effects. Black arrows represent upregulation and red arrows represent downregulation in COVID-19. ACE2, angiotensin-converting enzyme 2; ATR1, angiotensin II receptor 1; cACE2, circulatory angiotensin-converting enzyme 2; MasR, mitochondrial assembly receptor; RAAS, rennin-angiotensin-aldosterone system; TMPRSS2, transmembrane protease serine 2. Source: Refs 17-19.

Figure 1: Pathogenesis of SARS-CoV-2 in COVID-19.The S1 subunit of spike S protein on the virus surface engages with membrane-bound cellular receptor carboxypeptidase ACE2 present over the cell membrane of lung epithelial cells (pulmonary alveolar type II cells), and S2 subunit stalk helps in cell fusion. TMPRSS2 protease aids in the attachment of ACE2 with virus S protein. After entry inside the cell, the virus replicates and destroys ACE2. The decrease in ACE2 (transmembranous and circulatory) perpetuates the RAAS pathway. Increase in angiotensin II levels in COVID-19 causes widespread injury by activation of ATR1 receptors. Activation of ATR1 causes vasoconstriction, inflammation, endothelial dysfunction, acute lung injury and myocardial injury. The physiological function of ACE2 is to degrade angiotensin II to angiotensin 1-7, and angiotensin I to angiotensin 1-9. Angiotensin 1-7 acts on MasR receptors on cell membranes, and has vasodilatory and antifibrotic effects. Black arrows represent upregulation and red arrows represent downregulation in COVID-19. ACE2, angiotensin-converting enzyme 2; ATR1, angiotensin II receptor 1; cACE2, circulatory angiotensin-converting enzyme 2; MasR, mitochondrial assembly receptor; RAAS, rennin-angiotensin-aldosterone system; TMPRSS2, transmembrane protease serine 2. <i>Source</i>: Refs 17-19.