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. 2022 Aug:147:105788.
doi: 10.1016/j.compbiomed.2022.105788. Epub 2022 Jun 30.

In-silico screening and in-vitro assay show the antiviral effect of Indomethacin against SARS-CoV-2

Rajkumar Chakraborty  1 , Gourab Bhattacharje  2 , Joydeep Baral  2 , Bharat Manna  3 , Jayati Mullick  4 , Basavaraj S Mathapati  4 , Priya Abraham  4 , Madhumathi J  5 , Yasha Hasija  6 , Amit Ghosh  7 , Amit Kumar Das  8
Affiliations

In-silico screening and in-vitro assay show the antiviral effect of Indomethacin against SARS-CoV-2

Rajkumar Chakraborty et al. Comput Biol Med. 2022 Aug.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the worldwide spread of coronavirus disease 19 (COVID-19), and till now, it has caused death to more than 6.2 million people. Although various vaccines and drug candidates are being tested globally with limited to moderate success, a comprehensive therapeutic cure is yet to be achieved. In this study, we applied computational drug repurposing methods complemented with the analyses of the already existing gene expression data to find better therapeutics in treatment and recovery. Primarily, we identified the most crucial proteins of SARS-CoV-2 and host human cells responsible for viral infection and host response. An in-silico screening of the existing drugs was performed against the crucial proteins for SARS-CoV-2 infection, and a few existing drugs were shortlisted. Further, we analyzed the gene expression data of SARS-CoV-2 in human lung epithelial cells and investigated the molecules that can reverse the cellular mRNA expression profiles in the diseased state. LINCS L1000 and Comparative Toxicogenomics Database (CTD) were utilized to obtain two sets of compounds that can be used to counter SARS-CoV-2 infection from the gene expression perspective. Indomethacin, a nonsteroidal anti-inflammatory drug (NSAID), and Vitamin-A were found in two sets of compounds, and in the in-silico screening of existing drugs to treat SARS-CoV-2. Our in-silico findings on Indomethacin were further successfully validated by in-vitro testing in Vero CCL-81 cells with an IC50 of 12 μM. Along with these findings, we briefly discuss the possible roles of Indomethacin and Vitamin-A to counter the SARS-CoV-2 infection in humans.

Keywords: COVID-19; Differential gene expression; Drug repurposing; Indomethacin; SARS-CoV-2; Virtual screening.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Fig. 1
Fig. 1
Flow chart representing steps followed in shortlisting available SARS-Cov2-Human interacting partners.
Fig. 2
Fig. 2
CTD-Gene set data mapping pipeline.
Fig. 3
Fig. 3
The number of total drug molecules with binding energy < −5 kcal/mol for (a) Host targets and (b) Viral targets.
Fig. 4
Fig. 4
Differentially expressed genes in NHBE cell lines.
Fig. 5
Fig. 5
Number of molecules retrieved from various data sets.
Fig. 6
Fig. 6
Host targets human heme oxygenase-1, human sirtuin homolog 5, human glutathione peroxidase-1, human insulin degrading enzyme, catalytic and ubiquitin-associated domains of MARK-1/PAR-1, kinase and ubiquitin-associated domains of MARK3/PAR-1, NTF2 domains of Ras GTPase activating protein-binding domain, human plakophilin-2, Ubiquitin-protein ligase Mib1, G3BP2 NTF2-like domain, SmgGDS-558, and Angiotensin-converting enzyme 2 are docked with Indomethacin and their interactive residues at the active sites are shown in the images. Detailed interactions are listed in supplementary file 6.
Fig. 7
Fig. 7
Viral targets NSP-15, NSP-16/10, Papain like protease, Spike S1, Main protease, and RNA dependent RNA polymerase (RdRp) are docked with Indomethacin and their interactive residues at the active sites are shown in the images. Detailed interactions are listed in supplementary file 7.
Fig. 8
Fig. 8
Effect of Indomethacin treatment on Vero CCL-81 cells infected with SARS-CoV-2. Vero CCL-81 cells were infected with SARS-CoV-2 and treated with different concentrations of Indomethacin for 72 h. Virus control (VC) was not treated with the drug. RNA isolated from the respective cells after 72 h were subjected to qRT-PCR for the RdRp-2 gene target. All data are expressed as mean ± SD (standard deviation) for n = 3.
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References

    1. Abdellatif K.R.A., et al. New indomethacin analogs as selective COX-2 inhibitors: synthesis, COX-1/2 inhibitory activity, anti-inflammatory, ulcerogenicity, histopathological, and docking studies. Arch. Pharm. 2021;354 - PubMed
    1. Abd El-Mageed H.R., et al. In silico evaluation of different flavonoids from medicinal plants for their potency against SARS-CoV-2. Biologics. 2021;1:416–434. 1, 416–434 (2021)
    1. Elmaaty Ayman Abo, et al. Computational insights on the potential of some NSAIDs for treating COVID-19: priority set and lead optimization. Molecules. 2021;26(12):3772. - PMC - PubMed
    1. Aibana O., et al. Impact of vitamin A and carotenoids on the risk of tuberculosis progression. Clin. Infect. Dis. 2017;65:900–909. - PMC - PubMed
    1. Al-Horani R.A., Kar S. Potential anti-SARS-CoV-2 therapeutics that target the post-entry stages of the viral life cycle: a comprehensive review. Viruses. 2020;12 - PMC - PubMed