The AI-discovered aetiology of COVID-19 and rationale of the irinotecan+ etoposide combination therapy for critically ill COVID-19 patients #MMPMID33254502
Lovetrue B
Med Hypotheses 2020[Nov]; 144 (?): 110180 PMID33254502show ga
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.
|*COVID-19 Drug Treatment[MESH]
|COVID-19/*etiology[MESH]
|Comorbidity[MESH]
|Critical Illness[MESH]
|Disease Outbreaks[MESH]
|Disease Progression[MESH]
|Drug Discovery[MESH]
|Drug Therapy, Combination[MESH]
|Etoposide/*administration & dosage[MESH]
|Humans[MESH]
|Irinotecan/*administration & dosage[MESH]
|SARS-CoV-2/drug effects/physiology[MESH]
|Sepsis/physiopathology[MESH]
|Signal Transduction[MESH]
|Topoisomerase I Inhibitors/administration & dosage[MESH]
|Topoisomerase II Inhibitors/administration & dosage[MESH]
free
free
free
Med+Hypotheses 2020 ; 144 (?): 110180
