Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 4 de 4
STAR Protoc ; 3(3): 101648, 2022 09 16.
Article in English | MEDLINE | ID: covidwho-1967230


Here, we describe a bioinformatics pipeline that evaluates the interactions between coagulation-related proteins and genetic variants with SARS-CoV-2 proteins. This pipeline searches for host proteins that may bind to viral protein and identifies and scores the protein genetic variants to predict the disease pathogenesis in specific subpopulations. Additionally, it is able to find structurally similar motifs and identify potential binding sites within the host-viral protein complexes to unveil viral impact on regulated biological processes and/or host-protein impact on viral invasion or reproduction. For complete details on the use and execution of this protocol, please refer to Holcomb et al. (2021).

COVID-19 , SARS-CoV-2 , Binding Sites , COVID-19/genetics , Host Microbial Interactions , Humans , SARS-CoV-2/genetics , Viral Proteins/genetics
Sci Rep ; 12(1): 11388, 2022 07 06.
Article in English | MEDLINE | ID: covidwho-1921711


The emergence of the novel SARS-CoV-2 virus is the most important public-health issue of our time. Understanding the diverse clinical presentations of the ensuing disease, COVID-19, remains a critical unmet need. Here we present a comprehensive listing of the diverse clinical indications associated with COVID-19. We explore the theory that anti-SARS-CoV-2 antibodies could cross-react with endogenous human proteins driving some of the pathologies associated with COVID-19. We describe a novel computational approach to estimate structural homology between SARS-CoV-2 proteins and human proteins. Antibodies are more likely to interrogate 3D-structural epitopes than continuous linear epitopes. This computational workflow identified 346 human proteins containing a domain with high structural homology to a SARS-CoV-2 Wuhan strain protein. Of these, 102 proteins exhibit functions that could contribute to COVID-19 clinical pathologies. We present a testable hypothesis to delineate unexplained clinical observations vis-à-vis COVID-19 and a tool to evaluate the safety-risk profile of potential COVID-19 therapies.

Antibody Formation , COVID-19 , Cross Reactions , Epitopes , Humans , SARS-CoV-2
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