Abstract

BackgroundThe emergence and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in thelate 2019 has caused a devastating global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19). Although vaccines have been and are being developed, they are not accessible to everyone and not everyone can receive these vaccines. Also, it typically takes more than 10 years until a new therapeutic agent is approved for usage. Therefore, repurposing of known drugs can lend itself well as a key approach for significantly expediting the development of new therapies for COVID-19.MethodsWe have incorporated machine learning-based computational tools and in silico models into the drug discovery process to predict Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles of 90 potential drugs for COVID-19 treatment identified from two independent studies mainly with the purpose of mitigating late-phase failures because of inferior pharmacokinetics and toxicity.ResultsHere, we summarize the cardiotoxicity and general toxicity profiles of 90 potential drugs for COVID-19 treatment and outline the risks of repurposing and propose a stratification of patients accordingly. We shortlist a total of five compounds based on their non-toxic properties.ConclusionIn summary, this manuscript aims to provide a potentially useful source of essential knowledge on toxicity assessment of 90 compounds for healthcare practitioners and researchers to find off-label alternatives for the treatment for COVID-19. The majority of the molecules discussed in this manuscript have already moved into clinical trials and thus their known pharmacological and human safety profiles are expected to facilitate a fast track preclinical and clinical assessment for treating COVID-19.

Highlights

  • IntroductionThe emergence and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in thelate 2019 has caused a devastating global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19)

  • The emergence and rapid spread of SARS-CoV-2 in thelate 2019 has caused a devastating global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19)

  • Since December 2019, much of the world has suffered from the outbreak of coronavirus disease 2019 (COVID19), the disease caused by a novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) [1]

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Summary

Introduction

The emergence and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in thelate 2019 has caused a devastating global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19). One of the crucial threats of COVID-19 is the combination of respiratory failure and cardiovascular complications combined with widespread endothelial dysfunction and severe inflammation. It appears that an overproduction of pro-inflammatory cytokines (known as “cytokine storm”) that can be detected with interleukins and tumor necrosis biomarkers, is observed in the lungs of severely ill COVID-19 patients [3]. SARS-CoV-2 spike proteins bind to ACE2 receptor proteins on the host cell surface, perceived as angiotensin converting enzyme 2 (ACE2)

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