tetano
Editor, Senior Moderator
Genes (Basel)
. 2020 Dec 25;12(1):E19.
doi: 10.3390/genes12010019.
Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy
Aleksei Zarubin[SUP] 1 [/SUP], Vadim Stepanov[SUP] 1 [/SUP], Anton Markov[SUP] 1 [/SUP], Nikita Kolesnikov[SUP] 1 [/SUP], Andrey Marusin[SUP] 1 [/SUP], Irina Khitrinskaya[SUP] 1 [/SUP], Maria Swarovskaya[SUP] 1 [/SUP], Sergey Litvinov[SUP] 2 [/SUP], Natalia Ekomasova[SUP] 2 [/SUP], Murat Dzhaubermezov[SUP] 2 [/SUP], Nadezhda Maksimova[SUP] 3 [/SUP], Aitalina Sukhomyasova[SUP] 3 [/SUP], Olga Shtygasheva[SUP] 4 [/SUP], Elza Khusnutdinova[SUP] 2 [/SUP], Magomed Radzhabov[SUP] 5 [/SUP], Vladimir Kharkov[SUP] 1 [/SUP]
Affiliations
Abstract
The human serine protease serine 2 TMPRSS2 is involved in the priming of proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a possible target for COVID-19 therapy. The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data from 76 human populations demonstrates that a functionally significant missense mutation in exon 6/7 in the TMPRSS2 gene is found in many human populations at relatively high frequencies, with region-specific distribution patterns. The frequency of the missense mutation encoded by rs12329760, which has previously been found to be associated with prostate cancer, ranged between 10% and 63% and was significantly higher in populations of Asian origin compared with European populations. In addition to single-nucleotide polymorphisms, two copy number variants were detected in the TMPRSS2 gene. A number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. Several well-studied drugs can downregulate the expression of TMPRSS2 in human cells, including acetaminophen (paracetamol) and curcumin. Thus, the interactions of TMPRSS2 with SARS-CoV-2, together with its structural variability, gene-gene interactions, expression regulation profiles, and pharmacogenomic properties, characterize this gene as a potential target for COVID-19 therapy.
Keywords: ACE2; BSG; COVID-19; SARS-CoV-2; SNV; TMPRSS2; expression; pharmacotranscriptomics.
. 2020 Dec 25;12(1):E19.
doi: 10.3390/genes12010019.
Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy
Aleksei Zarubin[SUP] 1 [/SUP], Vadim Stepanov[SUP] 1 [/SUP], Anton Markov[SUP] 1 [/SUP], Nikita Kolesnikov[SUP] 1 [/SUP], Andrey Marusin[SUP] 1 [/SUP], Irina Khitrinskaya[SUP] 1 [/SUP], Maria Swarovskaya[SUP] 1 [/SUP], Sergey Litvinov[SUP] 2 [/SUP], Natalia Ekomasova[SUP] 2 [/SUP], Murat Dzhaubermezov[SUP] 2 [/SUP], Nadezhda Maksimova[SUP] 3 [/SUP], Aitalina Sukhomyasova[SUP] 3 [/SUP], Olga Shtygasheva[SUP] 4 [/SUP], Elza Khusnutdinova[SUP] 2 [/SUP], Magomed Radzhabov[SUP] 5 [/SUP], Vladimir Kharkov[SUP] 1 [/SUP]
Affiliations
- PMID: 33375616
- DOI: 10.3390/genes12010019
Abstract
The human serine protease serine 2 TMPRSS2 is involved in the priming of proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a possible target for COVID-19 therapy. The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data from 76 human populations demonstrates that a functionally significant missense mutation in exon 6/7 in the TMPRSS2 gene is found in many human populations at relatively high frequencies, with region-specific distribution patterns. The frequency of the missense mutation encoded by rs12329760, which has previously been found to be associated with prostate cancer, ranged between 10% and 63% and was significantly higher in populations of Asian origin compared with European populations. In addition to single-nucleotide polymorphisms, two copy number variants were detected in the TMPRSS2 gene. A number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. Several well-studied drugs can downregulate the expression of TMPRSS2 in human cells, including acetaminophen (paracetamol) and curcumin. Thus, the interactions of TMPRSS2 with SARS-CoV-2, together with its structural variability, gene-gene interactions, expression regulation profiles, and pharmacogenomic properties, characterize this gene as a potential target for COVID-19 therapy.
Keywords: ACE2; BSG; COVID-19; SARS-CoV-2; SNV; TMPRSS2; expression; pharmacotranscriptomics.