Preprint Hypothesis Version 1 Preserved in Portico This version is not peer-reviewed

The AI-Discovered Aetiology of COVID-19 and Rationale of the Irinotecan+Etoposide Combination Therapy for Critically Ill COVID-19 Patients

Version 1 : Received: 20 March 2020 / Approved: 23 March 2020 / Online: 23 March 2020 (06:56:57 CET)

A peer-reviewed article of this Preprint also exists.

Journal reference: Medical Hypotheses 2020
DOI: 10.1016/j.mehy.2020.110180


We present the AI-discovered aetiology of COVID-19, based on a precise disease model of COVID-19 built under five weeks that best matches the epidemiological characteristics, transmission dynamics, clinical features, and biological properties of COVID-19 and consistently explains the rapidly expanding COVID-19 literature. We present that SARS-CoV-2 implements a unique unbiased survival strategy of balancing viral replication with viral spread by increasing its dependence on (i) ACE2-expressing cells for viral entry and spread, (ii) PI3K signaling in ACE2-expressing cells for viral replication and egress, and (iii) viral-non-structural-and-accessory-protein-dependent immunomodulation to balance viral spread and viral replication. We further propose the combination of irinotecan (an in-market topoisomerase I inhibitor) and etoposide (an in-market topoisomerase IIinhibitor) could potentially be an exceptionally effective treatment to protect critically ill patients from death caused by COVID-19-specific cytokine storms triggered by sepsis, ARDS, and other fatal comorbidities.


Aetiology; Treatment; Cytokine Storm; ICU; COVID-19; ACE2; Irinotecan; Etoposide



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