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Review
. 2022 Jul 14:13:935399.
doi: 10.3389/fphar.2022.935399. eCollection 2022.

Use of Tox21 Screening Data to Evaluate the COVID-19 Drug Candidates for Their Potential Toxic Effects and Related Pathways

Srilatha Sakamuru  1 , Ruili Huang  1 , Menghang Xia  1
Affiliations
Review

Use of Tox21 Screening Data to Evaluate the COVID-19 Drug Candidates for Their Potential Toxic Effects and Related Pathways

Srilatha Sakamuru et al. Front Pharmacol. .

Abstract

Currently, various potential therapeutic agents for coronavirus disease-2019 (COVID-19), a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are being investigated worldwide mainly through the drug repurposing approach. Several anti-viral, anti-bacterial, anti-malarial, and anti-inflammatory drugs were employed in randomized trials and observational studies for developing new therapeutics for COVID-19. Although an increasing number of repurposed drugs have shown anti-SARS-CoV-2 activities in vitro, so far only remdesivir has been approved by the US FDA to treat COVID-19, and several other drugs approved for Emergency Use Authorization, including sotrovimab, tocilizumab, baricitinib, paxlovid, molnupiravir, and other potential strategies to develop safe and effective therapeutics for SARS-CoV-2 infection are still underway. Many drugs employed as anti-viral may exert unwanted side effects (i.e., toxicity) via unknown mechanisms. To quickly assess these drugs for their potential toxicological effects and mechanisms, we used the Tox21 in vitro assay datasets generated from screening ∼10,000 compounds consisting of approved drugs and environmental chemicals against multiple cellular targets and pathways. Here we summarize the toxicological profiles of small molecule drugs that are currently under clinical trials for the treatment of COVID-19 based on their in vitro activities against various targets and cellular signaling pathways.

Keywords: COVID-19; coronavirus; drugs; high throughput screening; in vitro assay.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Activity of the drugs from Tox21 screenings. In the heat map, each column is an assay readout and each row is a drug. The heatmap is colored by the activity. The darkest of red and blue indicates the most active agonists and antagonists respectively. The other shades of red and blue indicates the respective inconclusives and in majority of the assays the drugs are inactive.
FIGURE 2
FIGURE 2
Cytotoxicity of the drugs from Tox21 screenings. In the heat map, each row is an assay readout and each column is a drug. The heatmap is colored by the activity. The different shades of blue indicates the cytotoxicity of the drugs in a particular assay. The cytotoxic assays performed for Tox21 screenings are grouped mainly into four categories- CellTiter-Fluor, CellTiter-Glo, CellTox-Green, and RT Cell-Viability and further subgroups are the cell types used for each assay.
See this image and copyright information in PMC

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