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Hub AOP (AOP430) to model viral biology of infection: entry to transmission
Citation:
Mayasich, S., M. João Amorim, L. Clerbaux, A. Paini, N. Parissis, Y. Jun Kim, AND P. Nymark. Hub AOP (AOP430) to model viral biology of infection: entry to transmission. 5th (Final) Workshop: Modelling the pathogenesis of COVID-19 using the Adverse Outcome Pathway (CIAO), NA, MN, February 08 - 09, 2023. https://doi.org/10.23645/epacomptox.22049186
Impact/Purpose:
Presentation to the Workshop: Modelling the pathogenesis of COVID-19 using the Adverse Outcome Pathway (CIAO) February 2023. After approximately three years since the start of the pandemic, this is the fifth and final workshop for the CIAO international effort to model the pathogenesis of COVID-19. The aim has been to organize literature, identify data gaps and characterize the disease using the Adverse Outcome Pathway (AOP) framework which was developed for use in toxicology. The AOPs have been found to be a unifying platform leading to collaborations to protect human health and the environment from COVID-19 and future pandemics. At this time the group wraps up the formal association and reflects on the theme of what we were expecting, what we achieved and actions for the future. The AOP 430 presentation takes up this theme to emphasize potential applications of the knowledge gained and data gaps to be addressed in the host cell entry to transmission events of SARS-CoV-2 viral infection.
Description:
Several AOPs have been developed to coalesce literature-derived information on separate adverse outcomes of COVID-19, including acute respiratory distress, hyperinflammation, thrombosis, and gut dysbiosis, to name a few. All start with the molecular initiating event of the viral spike protein binding to the host cell angiotensin converting enzyme 2 (ACE2) receptor and the key event of cell entry. Many also acknowledge the key event of antagonism of the innate immune interferon antiviral response that is crucial to allowing the virus to replicate unchecked. These events are captured in AOP 430, “Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation,” which has become a hub AOP. The adverse outcome is viral infection and host-to-host transmission, proliferated, which emphasizes the zoonotic aspect of the disease and the need to define the taxonomic domain of applicability and characterize the intermediate hosts. A poster on this CIAO-inspired ongoing project which uses EPA’s SeqAPASS bioinformatic tool was presented at the Society of Environmental Toxicology and Chemistry meeting in November 2022. A manuscript on AOP 430 is also in preparation as an AOP Report to be submitted to the journal Environmental Toxicology and Chemistry. Immunotoxicants like per- and polyfluoroalkyl substances (PFAS) and air pollutants, which have been linked to COVID-19 incidence and susceptibility, are discussed.
URLs/Downloads:
DOI: Hub AOP (AOP430) to model viral biology of infection: entry to transmission
2-8-2023_CIAO_COVID_WORKSHOP_AOP430_MAYASICH.PDF (PDF, NA pp, 1964.582 KB, about PDF)