ACE2 Homo-dimerization, Human Genomic variants and Interaction of Host Proteins Explain High Population Specific Differences in Outcomes of COVID19

BioRxiv : the Preprint Server for Biology
Swarkar SharmaE. Rai


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive single stranded RNA virus that causes a highly contagious Corona Virus Disease (COVID19). Entry of SARS-CoV-2 in human cells depends on binding of the viral spike (S) proteins to cellular receptor Angiotensin-converting enzyme 2 (ACE2) and on S protein priming by host cell serine protease TMPRSS2. Recently COVID19 has been declared pandemic by World Health Organization yet high differences in disease outcomes across countries have been seen. We provide evidences based on analyses of existing public datasets and by using various in-silico approaches to explain some of these as factors that may explain population level differences. One of the key factors might be entry of virus in host cells due to differential interaction of viral proteins with host cell proteins due to different genetic backgrounds. Based on our findings, we conclude that higher expression of ACE2 facilitated by natural variations, acting as Expression quantitative trait loci (eQTLs) and with different frequencies in different populations, results in ACE2 homo-dimerization which is disadvantageous for TMPRSS2 mediated cleavage of ACE2 and becomes more difficult in presence of broad neutr...Continue Reading

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