Preprint Hypothesis Version 1 Preserved in Portico This version is not peer-reviewed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

Lovetrue, B. The AI-Discovered Aetiology of COVID-19 and Rationale of the Irinotecan+ Etoposide Combination Therapy for Critically Ill COVID-19 Patients. Medical Hypotheses, 2020, 144, 110180. https://doi.org/10.1016/j.mehy.2020.110180. Lovetrue, B. The AI-Discovered Aetiology of COVID-19 and Rationale of the Irinotecan+ Etoposide Combination Therapy for Critically Ill COVID-19 Patients. Medical Hypotheses, 2020, 144, 110180. https://doi.org/10.1016/j.mehy.2020.110180.

Abstract

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.

Keywords

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

Subject

Biology and Life Sciences, Virology

Comments (0)

Comment 1
Received: 14 April 2020
Commenter: Namnama P. Villarta-De Dios
The commenter has declared there is no conflict of interests.
Comment: Hi. I am interested in the possible benefit of etoposide in the management of cytokine storm among COVID-19 patients. I am part of a group (University of the Philippines College of Medicine) evaluating the literature on anything related to the pandemic. May I ask about the clinical trial you mentioned in the article -- has it commenced? Do you have a writeup on that? Would like to read that as well.

Kind regards,
Nama De Dios
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