ACE2 and FURIN variants are potential predictors of SARS-CoV-2 outcome: A time to implement precision medicine against COVID-19

Abstract The severity of the new COVID-19 pandemic caused by SARS-CoV-2 virus is strikingly variable in different global populations. uses ACE2 as a cell receptor, TMPRSS2 protease, and FURIN peptidase to invade human cells. Here, we investigated 1,378 whole-exome sequences individuals from Middle Eastern populations (Kuwait, Qatar, Iran) explore natural variations ACE2, TMPRSS2, genes. We identified two activating variants (K26R N720D) gene that are more common Europeans than Eastern, East Asian, African postulate K26R can activate facilitate binding S-protein RBD while N720D enhances cutting and, ultimately, viral entry. also detected deleterious frequent but not European This study highlights specific genetic genes may explain clinical disparity. showed structural evidence functionality these increase aggressiveness. Finally, our data illustrate significant correlation between people origins be further explored variation infection mortality rates globally.