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Identification of potential SARS-CoV-2 intermediate host species using SeqAPASS
Citation:
Mayasich, S. AND C. LaLone. Identification of potential SARS-CoV-2 intermediate host species using SeqAPASS. SETAC North America, Pittsburgh, PA, November 13 - 17, 2022. https://doi.org/10.23645/epacomptox.21559485
Impact/Purpose:
Poster presented to the Society of Environmental Toxicology and Chemistry (SETAC) annual meeting November 2022. This focuses on the effort to identify intermediate host species of the zoonotic virus SARS-CoV-2 that is the pathogen causing the current COVID-19 disease pandemic. The study uses EPA’s Sequence Alignment to Predict Across-Species Susceptibility (SeqAPASS) bioinformatic tool to compare host antiviral protein sequences across species. Sally Mayasich will present the work at a session she is co-chairing with Eric Villegas (EPA-Cincinnati), on Leveraging and adapting environmental methods and monitoring tools for COVID-19 public health research and surveillance. The session intends to engage stakeholders in both human and ecosystem health, potentially exploiting One Health, New Approach Methodologies (NAMs), bioinformatics tools, development of Adverse Outcome Pathways, and other unifying platforms and frameworks leading to collaborations to protect human health and the environment from COVID-19 and future pandemics. Presentation in this session will showcase a novel use of SeqAPASS to study host-pathogen protein-protein interactions across species with the hope of identifying intermediate hosts for environmental surveillance efforts
Description:
COVID-19 is a zoonotic disease caused by infection of the coronavirus SARS-CoV-2. SARS-CoV-2 has been demonstrated to pass from animals to humans and from humans to animals; infections have been detected in animals in North America including minks, ferrets, white-tailed deer, big cats, and domestic animals. SARS-CoV-2 enters the cells of host animals and replicates to transmissible levels by evading host innate immune responses through a variety of interactions with host proteins. The viral spike protein binds to the angiotensin converting enzyme 2 (ACE2) protein as a receptor on the host cell surface to enter the cell. The virus uses the host cell machinery to translate its RNA genome into proteins that block host proteins in the interferon-I (IFN-I) antiviral pathway, a crucial process allowing the virus to replicate. Understanding conservation of these host antiviral proteins across species could aid in determining which species are likely to serve as reservoirs or intermediate hosts. The web-based US EPA Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool facilitates the comparison of proteins to evaluate conservation across hundreds of species rapidly. In this novel application, critical domains and amino acids involved in protein-protein interactions between viral proteins and human host antiviral proteins were identified. Conservation of antiviral protein sequences across species compared to the human proteins was evaluated to assess their vulnerability to attack by SARS-CoV-2 viral proteins. From a literature review, IFN-I antiviral pathway protein targets such as mitochondrial antiviral signaling protein (MAVS), IFN regulatory factor 3 (IRF3), and IFN-stimulated gene 15 (ISG-15) were selected for evaluation. The SeqAPASS Level 1 primary amino acid sequence comparison indicated a lack of conservation of these proteins in non-mammals. Further, functional domains and critical amino acids in the human IFN-protein-to-viral-protein interaction sites were queried and results were evaluated from species that had previously been studied empirically for COVID-19 infectability or bioinformatically for ACE2 binding potential. A list of mammals exhibiting structural conservation for these proteins could then be mapped to geographic regions across the United States to inform zoonotic disease surveillance efforts. This abstract neither constitutes nor necessarily reflects USEPA policy.
URLs/Downloads:
DOI: Identification of potential SARS-CoV-2 intermediate host species using SeqAPASS
MAYASICH_SETAC_2022_SEQAPASS_COVID_POSTER_72X44_STICS_FINAL.PDF (PDF, NA pp, 4104.679 KB, about PDF)