Your browser doesn't support javascript.
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.
  • Zarubin A; Tomsk National Medical Research Center, Research Institute for Medical Genetics, 634050 Tomsk, Russia.
  • Stepanov V; Tomsk National Medical Research Center, Research Institute for Medical Genetics, 634050 Tomsk, Russia.
  • Markov A; Tomsk National Medical Research Center, Research Institute for Medical Genetics, 634050 Tomsk, Russia.
  • Kolesnikov N; Tomsk National Medical Research Center, Research Institute for Medical Genetics, 634050 Tomsk, Russia.
  • Marusin A; Tomsk National Medical Research Center, Research Institute for Medical Genetics, 634050 Tomsk, Russia.
  • Khitrinskaya I; Tomsk National Medical Research Center, Research Institute for Medical Genetics, 634050 Tomsk, Russia.
  • Swarovskaya M; Tomsk National Medical Research Center, Research Institute for Medical Genetics, 634050 Tomsk, Russia.
  • Litvinov S; Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, 450000 Ufa, Russia.
  • Ekomasova N; Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, 450000 Ufa, Russia.
  • Dzhaubermezov M; Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, 450000 Ufa, Russia.
  • Maksimova N; Medical Institute, North-Eastern Federal University, 677000 Yakutsk, Russia.
  • Sukhomyasova A; Medical Institute, North-Eastern Federal University, 677000 Yakutsk, Russia.
  • Shtygasheva O; Medical-Psychological-Social Institute, Katanov State University of Khakassia, 655017 Abakan, Russia.
  • Khusnutdinova E; Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, 450000 Ufa, Russia.
  • Radzhabov M; Laboratory of Genomic Medicine, Dagestan State Medical University, 367000 Makhachkala, Russia.
  • Kharkov V; Tomsk National Medical Research Center, Research Institute for Medical Genetics, 634050 Tomsk, Russia.
Genes (Basel) ; 12(1)2020 12 25.
Article in English | MEDLINE | ID: covidwho-1021948
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Gene Expression Regulation, Enzymologic / Molecular Targeted Therapy / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment Type of study: Diagnostic study / Observational study / Prognostic study Topics: Variants Limits: Humans Country/Region as subject: Asia / Europa Language: English Year: 2020 Document Type: Article Affiliation country: Genes12010019

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Gene Expression Regulation, Enzymologic / Molecular Targeted Therapy / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment Type of study: Diagnostic study / Observational study / Prognostic study Topics: Variants Limits: Humans Country/Region as subject: Asia / Europa Language: English Year: 2020 Document Type: Article Affiliation country: Genes12010019