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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
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
Sci Rep ; 10(1): 15643, 2020 09 24.
Article in English | MEDLINE | ID: covidwho-796202


As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses, for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.

Betacoronavirus/genetics , Coronavirus Infections/prevention & control , Nucleocapsid Proteins/genetics , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/genetics , Viral Vaccines/immunology , Base Sequence , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Nucleocapsid Proteins , Genome, Viral/genetics , Humans , Nucleocapsid Proteins/immunology , Phosphoproteins , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Inactivated/immunology , Whole Genome Sequencing