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Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy

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...

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Autores principales: Zarubin, Aleksei, Stepanov, Vadim, Markov, Anton, Kolesnikov, Nikita, Marusin, Andrey, Khitrinskaya, Irina, Swarovskaya, Maria, Litvinov, Sergey, Ekomasova, Natalia, Dzhaubermezov, Murat, Maksimova, Nadezhda, Sukhomyasova, Aitalina, Shtygasheva, Olga, Khusnutdinova, Elza, Radzhabov, Magomed, Kharkov, Vladimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823984/
https://www.ncbi.nlm.nih.gov/pubmed/33375616
http://dx.doi.org/10.3390/genes12010019
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author Zarubin, Aleksei
Stepanov, Vadim
Markov, Anton
Kolesnikov, Nikita
Marusin, Andrey
Khitrinskaya, Irina
Swarovskaya, Maria
Litvinov, Sergey
Ekomasova, Natalia
Dzhaubermezov, Murat
Maksimova, Nadezhda
Sukhomyasova, Aitalina
Shtygasheva, Olga
Khusnutdinova, Elza
Radzhabov, Magomed
Kharkov, Vladimir
author_facet Zarubin, Aleksei
Stepanov, Vadim
Markov, Anton
Kolesnikov, Nikita
Marusin, Andrey
Khitrinskaya, Irina
Swarovskaya, Maria
Litvinov, Sergey
Ekomasova, Natalia
Dzhaubermezov, Murat
Maksimova, Nadezhda
Sukhomyasova, Aitalina
Shtygasheva, Olga
Khusnutdinova, Elza
Radzhabov, Magomed
Kharkov, Vladimir
author_sort Zarubin, Aleksei
collection PubMed
description 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.
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spelling pubmed-78239842021-01-24 Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy Zarubin, Aleksei Stepanov, Vadim Markov, Anton Kolesnikov, Nikita Marusin, Andrey Khitrinskaya, Irina Swarovskaya, Maria Litvinov, Sergey Ekomasova, Natalia Dzhaubermezov, Murat Maksimova, Nadezhda Sukhomyasova, Aitalina Shtygasheva, Olga Khusnutdinova, Elza Radzhabov, Magomed Kharkov, Vladimir Genes (Basel) Article 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. MDPI 2020-12-25 /pmc/articles/PMC7823984/ /pubmed/33375616 http://dx.doi.org/10.3390/genes12010019 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zarubin, Aleksei
Stepanov, Vadim
Markov, Anton
Kolesnikov, Nikita
Marusin, Andrey
Khitrinskaya, Irina
Swarovskaya, Maria
Litvinov, Sergey
Ekomasova, Natalia
Dzhaubermezov, Murat
Maksimova, Nadezhda
Sukhomyasova, Aitalina
Shtygasheva, Olga
Khusnutdinova, Elza
Radzhabov, Magomed
Kharkov, Vladimir
Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy
title Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy
title_full Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy
title_fullStr Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy
title_full_unstemmed Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy
title_short Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy
title_sort structural variability, expression profile, and pharmacogenetic properties of tmprss2 gene as a potential target for covid-19 therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823984/
https://www.ncbi.nlm.nih.gov/pubmed/33375616
http://dx.doi.org/10.3390/genes12010019
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