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. 2021 Oct 21;22(1):61.
doi: 10.1186/s40360-021-00519-5.

Computational determination of toxicity risks associated with a selection of approved drugs having demonstrated activity against COVID-19

Maral Aminpour  1 , Williams Ernesto Miranda Delgado  2 , Soren Wacker  2 , Sergey Noskov  2 , Michael Houghton  3 , D Lorne J Tyrrell  3 , Jack A Tuszynski  4
Affiliations

Computational determination of toxicity risks associated with a selection of approved drugs having demonstrated activity against COVID-19

Maral Aminpour et al. BMC Pharmacol Toxicol. .

Abstract

Background: 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). 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.

Methods: We 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.

Results: Here, 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.

Conclusion: In 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.

Keywords: COVID-19; Repurposing drugs, hERG); Toxicity.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Models in ADMET Predictor’s Toxicity Module
See this image and copyright information in PMC

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