The AI-discovered aetiology of COVID-19 and rationale of the irinotecan+ etoposide combination therapy for critically ill COVID-19 patients

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 II inhibitor) 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.

• Tipo de recurso: Article of investigation
• Fecha de publicación: 2020
• Institución: Universidad de Bogotá Jorge Tadeo Lozano
• Repositorio: Expeditio: repositorio UTadeo
• Idioma: eng
• OAI Identifier: oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/13618
• Acceso en línea: https://doi.org/10.1016/j.mehy.2020.110180; http://hdl.handle.net/20.500.12010/13618
• Palabra clave: Aetiology; Treatment; Cytokine storm; ICU; COVID-19; ACE2; Irinotecan; Etoposide; SARS-CoV-2; Síndrome respiratorio agudo grave; COVID-19; SARS-CoV-2; Coronavirus
• License: Abierto (Texto Completo)