Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 3 de 3
Arch Virol ; 166(8): 2089-2108, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1209235


The SARS-CoV-2 pandemic has become one of the most serious health concerns globally. Although multiple vaccines have recently been approved for the prevention of coronavirus disease 2019 (COVID-19), an effective treatment is still lacking. Our knowledge of the pathogenicity of this virus is still incomplete. Studies have revealed that viral factors such as the viral load, duration of exposure to the virus, and viral mutations are important variables in COVID-19 outcome. Furthermore, host factors, including age, health condition, co-morbidities, and genetic background, might also be involved in clinical manifestations and infection outcome. This review focuses on the importance of variations in the host genetic background and pathogenesis of SARS-CoV-2. We will discuss the significance of polymorphisms in the ACE-2, TMPRSS2, vitamin D receptor, vitamin D binding protein, CD147, glucose-regulated protein 78 kDa, dipeptidyl peptidase-4 (DPP4), neuropilin-1, heme oxygenase, apolipoprotein L1, vitamin K epoxide reductase complex 1 (VKORC1), and immune system genes for the clinical outcome of COVID-19.

COVID-19/genetics , ABO Blood-Group System/genetics , Angiotensin-Converting Enzyme 2/genetics , Apolipoprotein L1/genetics , Basigin/genetics , COVID-19/epidemiology , COVID-19/therapy , Dipeptidyl Peptidase 4/genetics , Endoplasmic Reticulum Chaperone BiP , Heat-Shock Proteins/genetics , Heme Oxygenase-1/genetics , Humans , Immunity/genetics , Neuropilin-1/genetics , Patient Outcome Assessment , Polymorphism, Genetic , Receptors, Calcitriol/genetics , SARS-CoV-2 , Serine Endopeptidases/genetics , Vitamin D-Binding Protein/genetics , Vitamin K Epoxide Reductases/genetics
PLoS Comput Biol ; 17(3): e1008805, 2021 03.
Article in English | MEDLINE | ID: covidwho-1181166


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.

Blood Coagulation , Blood Proteins/genetics , COVID-19/metabolism , Complement C1 Inhibitor Protein/genetics , Poly(A)-Binding Proteins/genetics , SARS-CoV-2/metabolism , Vitamin K Epoxide Reductases/genetics , Anticoagulants/administration & dosage , Blood Proteins/metabolism , COVID-19/physiopathology , COVID-19/virology , Complement C1 Inhibitor Protein/metabolism , Genome-Wide Association Study , Humans , Models, Molecular , Mutation , Poly(A)-Binding Proteins/metabolism , Protein Binding , SARS-CoV-2/genetics , Severity of Illness Index , Viral Proteins/metabolism , Vitamin K Epoxide Reductases/metabolism , Warfarin/administration & dosage
Med Hypotheses ; 144: 110218, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-728777


Covid-19, caused by SARS-CoV-2, has major world-wide health-related and socio-economic consequences. There are large disparities in the burden of Covid-19 with an apparent lower risk of poor outcomes in East Asians compared to populations in the West. A recent study suggested that Covid-19 leads to a severe extrahepatic vitamin K insufficiency, which could lead to impaired activation of extrahepatic proteins like endothelial anticoagulant protein S in the presence of normal hepatic procoagulant activity. This would be compatible with the enhanced thrombogenicity in severe Covid-19. The same study showed that vitamin K antagonists (VKA) that inhibit vitamin K recycling, had a greater impact on procoagulant activity than on the activation of extrahepatic vitamin K-dependent proteins during SARS-CoV-2 infections. A genetic polymorphism in the vitamin K epoxide reductase complex 1, VKORC1 -1639A, is particularly prevalent in East Asia and associates with low vitamin K recycling rates. Carriage of the allele may be regarded as bioequivalent to low-dose VKA use. We speculate that VKORC1 -1639A confers protection against thrombotic complications of Covid-19 and that differences in its allele frequency are partially responsible for the differences in Covid-19 severity between East and West.

COVID-19/genetics , Vitamin K Epoxide Reductases/genetics , Americas/epidemiology , COVID-19/complications , COVID-19/enzymology , Europe/epidemiology , Asia, Eastern/epidemiology , Gene Frequency , Humans , Models, Biological , Pandemics , Polymorphism, Single Nucleotide , SARS-CoV-2 , Severity of Illness Index , Thrombosis/etiology , Thrombosis/genetics , Thrombosis/prevention & control , Vitamin K/antagonists & inhibitors , Vitamin K Deficiency/etiology