Gene variants of coagulation related proteins that interact with SARS-CoV-2
| Autor: | Jacob Kames, Anton A. Komar, Michael DiCuccio, Ryan C. Hunt, Nobuko Hamasaki-Katagiri, Chava Kimchi-Sarfaty, Aikaterini Alexaki, Kyle Laurie, Nancy E. Hernandez, David D. Holcomb |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
RNA viruses
0301 basic medicine Viral Diseases Vitamin K RNA splicing Coronaviruses Organic chemistry Genome-wide association study Plasma protein binding 030204 cardiovascular system & hematology medicine.disease_cause Biochemistry Medical Conditions 0302 clinical medicine Medicine and Health Sciences Biology (General) Pathology and laboratory medicine Coronavirus Genetics Mutation Ecology Nucleotides Genomics Vitamins Medical microbiology Nucleic acids Physical sciences Chemistry Infectious Diseases Computational Theory and Mathematics Modeling and Simulation Viruses VKORC1 SARS CoV 2 Pathogens Research Article SARS coronavirus QH301-705.5 B vitamins Vitamin K Epoxide Reductase Complex Subunit 1 Biology Genome Complexity Microbiology Chemical compounds 03 medical and health sciences Cellular and Molecular Neuroscience Organic compounds medicine Non-coding RNA Molecular Biology Gene Ecology Evolution Behavior and Systematics SARS Natural antisense transcripts Biology and life sciences Binding protein Organisms Viral pathogens Computational Biology Covid 19 Introns Gene regulation Microbial pathogens MicroRNAs 030104 developmental biology RNA processing RNA Gene expression |
| Zdroj: | PLoS Computational Biology, Vol 17, Iss 3, p e1008805 (2021) PLoS Computational Biology |
| ISSN: | 1553-7358 |
| Popis: | Thrombosis is a recognized complication of Coronavirus disease of 2019 (COVID-19) and is often associated with poor prognosis. There is a well-recognized link between coagulation and inflammation, however, the extent of thrombotic events associated with COVID-19 warrants further investigation. Poly(A) Binding Protein Cytoplasmic 4 (PABPC4), Serine/Cysteine Proteinase Inhibitor Clade G Member 1 (SERPING1) and Vitamin K epOxide Reductase Complex subunit 1 (VKORC1), which are all proteins linked to coagulation, have been shown to interact with SARS proteins. We computationally examined the interaction of these with SARS-CoV-2 proteins and, in the case of VKORC1, we describe its binding to ORF7a in detail. We examined the occurrence of variants of each of these proteins across populations and interrogated their potential contribution to COVID-19 severity. Potential mechanisms, by which some of these variants may contribute to disease, are proposed. Some of these variants are prevalent in minority groups that are disproportionally affected by severe COVID-19. Therefore, we are proposing that further investigation around these variants may lead to better understanding of disease pathogenesis in minority groups and more informed therapeutic approaches. Author summary Increased blood clotting, especially in the lungs, is a common complication of COVID-19. Infectious diseases cause inflammation, which in turn can contribute to increased blood clotting. However, the extent of clot formation that is seen in the lungs of COVID-19 patients suggests that there may be a more direct link. We identified three human proteins that are involved indirectly in the blood clotting cascade and have been shown to interact with proteins of SARS virus, which is closely related to the novel coronavirus. We examined computationally the interaction of these human proteins with the viral proteins. We looked for genetic variants of these proteins and examined how they are distributed across populations. We investigated whether variants of these genes could impact severity of COVID-19. Further investigation around these variants may provide clues for the pathogenesis of COVID-19, particularly in minority groups. |
| Databáze: | OpenAIRE |
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