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

Abstract

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

Related Concepts

Metabolic Process, Cellular
Size
Brain
Ability to Perform Cognitive Activity
Metabolic Rate
Racial Group
Brain Neoplasms
Growth Arrest
Cognition
Mass Lesion of Brain

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

PLoS Computational Biology
Mauricio González-ForeroLaurent Lehmann
Current Biology : CB
Guido Barbujani, Massimo Pigliucci
American Journal of Human Biology : the Official Journal of the Human Biology Council
Britta KuberaManfred James Müller
© 2020 Meta ULC. All rights reserved