Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Advanced Adverse Outcome Pathways Potentially Bridging the Pathogenesis of COVID-19

Version 1 : Received: 2 January 2021 / Approved: 4 January 2021 / Online: 4 January 2021 (16:37:08 CET)

How to cite: kim, Y.; Park, C.G.; Lim, S.R.; Jun, I.; Lee, Y.O. Advanced Adverse Outcome Pathways Potentially Bridging the Pathogenesis of COVID-19. Preprints 2021, 2021010065 (doi: 10.20944/preprints202101.0065.v1). kim, Y.; Park, C.G.; Lim, S.R.; Jun, I.; Lee, Y.O. Advanced Adverse Outcome Pathways Potentially Bridging the Pathogenesis of COVID-19. Preprints 2021, 2021010065 (doi: 10.20944/preprints202101.0065.v1).

Abstract

Increasing global concern over COVID-19 has recently brought greater attention to studies due to the ease of person-to-person transmission and the current lack of effective antiviral therapy. Here, we proposed the application of the adverse outcome pathway (AOP) framework to support re-search on the pathogenesis of viral disease. We first constructed adverse outcome pathways (AOPs) applicable to COVID-19 management to understand whether the infection causes severe acute respiratory distress. Based on the AOP framework where mechanistic elucidation of the pathway from the interaction of chemicals (or viruses) to apical endpoints is represented, our COVID-19 AOP indicated that the molecular initiating event (MIE) was angiotensin-converting enzyme 2 (ACE2) interaction, and the key events (KEs) were the increased pro-inflammatory cytokines in immune cells, with increased mortality as an apical adverse outcome (AO). However, there is still limited information on the toxicity mechanisms of AOPs in COVID-19; therefore, detailed KEs and AOs on toxicity mechanisms will be required to fill these gaps in the data. This study demonstrated that the COVID-19 AOP framework is a suitable tool to design new drugs and to integrate crowded-sourced information for the battle against the COVID-19 pandemic.

Subject Areas

COVID-19; Angiotensin Converting Enzyme 2 (ACE2); Adverse outcome pathway(AOP); Molecular initiation Event (MIE); Key event (KE); Adverse Outcome (AO)

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