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

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.

Computational Insights and Virtual Screening of Repurposed FDA-Approved Drug Against SARS-CoV-2 Protease

“…All the compounds show negative carcinogenicity values. The negative hERG and Ames mutagenicity values prove that the compounds do not affect the potassium channels in the heart which in turn may lead to cardiac arrhythmia (Aminpour et al 2021 ).…”

COVID-19 GPH: tracking the contribution of genomics and precision health to the COVID-19 pandemic response

“…Genomic surveillance has documented the emergence and spread of the omicron and delta SARS-CoV-2 variants in Denmark [ 4 ] as well as the unique mutations that differ between these two variants [ 5 ]. Other studies have described the role of human genetic polymorphisms in COVID-19 susceptibility [ 6 ], the upregulation of proinflammatory cytokine genes in severe COVID-19 patients [ 7 ], and the toxicity profiles of 90 possible COVID-19 treatments using machine learning [ 8 ].…”

The Concomitant Use o f Melatonin and Bebtelovimab as a Treatment Strategy for Omicron and Future Variants of Concern

“…SARS-CoV-2 has developed more as the pandemic has spread, as expected. Numerous variants are considered to have been produced by selective pressures and viral adaptability during protracted, inadequately treated infections; some of these mutations dramatically reduce the efficacy of COVID-19 therapeutic countermeasures [3]. Variants of concern (VOC) form a highly observed subset of numerous SARS-CoV-2 variants.…”

“…Variants of concern (VOC) form a highly observed subset of numerous SARS-CoV-2 variants. This is because of their enhanced infectious potential, their high capacity to evade vaccination-induced immunity, and their tendency to reduce the efficacy of antibody-based therapies [3]. In addition, the Omicron variant was classified as a variant of concern by the World Health Organization in November 2021 [4].…”