ABSTRACT
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).
Subject(s)
COVID-19 , SARS-CoV-2 , Binding Sites , COVID-19/genetics , Host Microbial Interactions , Humans , SARS-CoV-2/genetics , Viral Proteins/geneticsABSTRACT
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.