First comprehensive computational analysis of functional consequences of TMPRSS2 SNPs in susceptibility to SARS-CoV-2 among different populations
- 1 June 2020
- journal article
- research article
- Published by Taylor & Francis Ltd in Journal of Biomolecular Structure and Dynamics
- Vol. 39 (10), 3576-3593
- https://doi.org/10.1080/07391102.2020.1767690
Abstract
Background & Objective: Current SARS-CoV-2 pandemy mortality created the hypothesis that some populations may be more susceptible to SARS-CoV-2. TMPRSS2 encodes a transmembrane serine protease which plays a crucial role in SARS-CoV-2 cell entry. Single nucleotide polymorphisms (SNPs) in TMPRSS2 might influence SARS-CoV2 entry into the cell. This study aimed to investigate the impact of SNPs on TMPRSS2 function and structure. Methods: In silico tools such as Ensembl, Gtex, ExPASY 2, GEPIA, CCLE, KEGG, and GO were engaged to characterize TMPRSS2 and it's expression profile. The functional effects of SNPs were analyzed by PolyPhen-2, PROVEN, SNAP2, SIFT, and HSF. Also, Phyre2, GOR IV, and PSIPRED were used to predict the secondary structure of TMPRSS2. Moreover, post translational modification (PTM) and secretory properties were analyzed through Modpredand Phobius, respectively. Finally, miRNA profiles were investigated by PolymiRTS and miRSNPs. Results: Out of 11184 retrieved SNPs from dbSNP, 92 showed a different frequency between Asians and other populations. Only 21 SNPs affected the function and structure of TMPRSS2 by influencing the protein folding, PTM, splicing, and miRNA function. Particularly, rs12329760 may create a de novo pocket protein. rs875393 can create a donor site, silencer and broken enhancer motifs. rs12627374 affects a wide spectrum of miRNAs profile. Conclusion: This study highlighted the role of TMPRSS2 SNPs and epigenetic mechanisms especially non-coding RNAs in appearance of different susceptibility to SARS-CoV-2 among different populations. Also, this study could pave the way to potential therapeutic implication of TMPRSS2 in designing antiviral drugs.Keywords
This publication has 58 references indexed in Scilit:
- TMPRSS2-ERG Expression Predicts Prostate Cancer Survival and Associates with Stromal BiomarkersPLOS ONE, 2014
- Androgen Regulation of the TMPRSS2 Gene and the Effect of a SNP in an Androgen Response ElementMolecular Endocrinology, 2013
- Simultaneous Treatment of Human Bronchial Epithelial Cells with Serine and Cysteine Protease Inhibitors Prevents Severe Acute Respiratory Syndrome Coronavirus EntryJournal of Virology, 2012
- Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancerBMC Cancer, 2008
- Suppression of androgen receptor-mediated gene expression by a sequence-specific DNA-binding polyamideProceedings of the National Academy of Sciences of the United States of America, 2007
- A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injuryNature Medicine, 2005
- Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptorBiochemical and Biophysical Research Communications, 2004
- Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesisThe Journal of Pathology, 2004
- Continuous regional application of protease inhibitor in the treatment of acute pancreatitisPancreatology, 2001
- Expression of Renin-Angiotensin System Components in the Heart, Kidneys, and Lungs of Rats With Experimental Heart FailureCirculation, 1995