Gene variants of coagulation related proteins that interact with SARS-CoV-2.

David Holcomb, Aikaterini Alexaki, Nancy Hernandez, Ryan Hunt, Kyle Laurie, Jacob Kames, Nobuko Hamasaki-Katagiri, Anton A Komar, Michael DiCuccio, Chava Kimchi-Sarfaty

PLoS computational biology 2021 Mar

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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.

Citation

David Holcomb, Aikaterini Alexaki, Nancy Hernandez, Ryan Hunt, Kyle Laurie, Jacob Kames, Nobuko Hamasaki-Katagiri, Anton A Komar, Michael DiCuccio, Chava Kimchi-Sarfaty. Gene variants of coagulation related proteins that interact with SARS-CoV-2. PLoS computational biology. 2021 Mar;17(3):e1008805