The AI-discovered Aetiology of COVID-19 and Rationale of the Irinotecan+ Etoposide Combination Therapy for Criti- cally Ill COVID-19 Patients

Lovetrue, Bragi

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 con- sistently 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 topoi- somerase I inhibitor) and etoposide (an in-market topoisomerase II inhibitor) could poten- tially 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.