Repurposing Didanosine as a Potential Treatment for COVID-19 Using Single-Cell RNA Sequencing Data

doi:10.1128/mSystems.00297-20

. 2020 Apr 14;5(2):e00297-20.

doi: 10.1128/mSystems.00297-20.

Repurposing Didanosine as a Potential Treatment for COVID-19 Using Single-Cell RNA Sequencing Data

Fadhl M Alakwaa¹

Affiliations

PMID: 32291351
PMCID: PMC7159901
DOI: 10.1128/mSystems.00297-20

Repurposing Didanosine as a Potential Treatment for COVID-19 Using Single-Cell RNA Sequencing Data

Fadhl M Alakwaa. mSystems. 2020.

. 2020 Apr 14;5(2):e00297-20.

doi: 10.1128/mSystems.00297-20.

Author

Fadhl M Alakwaa¹

Affiliation

¹ Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA alakwaaf@med.umich.edu.

PMID: 32291351
PMCID: PMC7159901
DOI: 10.1128/mSystems.00297-20

Abstract

As of today (7 April 2020), more than 81,000 people around the world have died from the coronavirus disease 19 (COVID-19) pandemic. There is no approved drug or vaccine for COVID-19, although more than 10 clinical trials have been launched to test potential drugs. In an urgent response to this pandemic, I developed a bioinformatics pipeline to identify compounds and drug candidates to potentially treat COVID-19. This pipeline is based on publicly available single-cell RNA sequencing (scRNA-seq) data and the drug perturbation database "Library of Integrated Network-Based Cellular Signatures" (LINCS). I developed a ranking score system that prioritizes these drugs or small molecules. The four drugs with the highest total score are didanosine, benzyl-quinazolin-4-yl-amine, camptothecin, and RO-90-7501. In conclusion, I have demonstrated the utility of bioinformatics for identifying drugs than can be repurposed for potentially treating COVID-19 patients.

Keywords: COVID-19; drug; repurposing.

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References

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[1] Zheng Y-Y, Ma Y-T, Zhang J-Y, Xie X. 5 March 2020. COVID-19 and the cardiovascular system. Nat Rev Cardiol doi:10.1038/s41569-020-0360-5. - DOI - PMC - PubMed

[2] Zheng Y-Y, Ma Y-T, Zhang J-Y, Xie X. 5 March 2020. COVID-19 and the cardiovascular system. Nat Rev Cardiol doi:10.1038/s41569-020-0360-5. - DOI - PMC - PubMed

[3] Reyfman PA, Walter JM, Joshi N, Anekalla KR, McQuattie-Pimentel AC, Chiu S, Fernandez R, Akbarpour M, Chen C-I, Ren Z, Verma R, Abdala-Valencia H, Nam K, Chi M, Han S, Gonzalez-Gonzalez FJ, Soberanes S, Watanabe S, Williams KJN, Flozak AS, Nicholson TT, Morgan VK, Winter DR, Hinchcliff M, Hrusch CL, Guzy RD, Bonham CA, Sperling AI, Bag R, Hamanaka RB, Mutlu GM, Yeldandi AV, Marshall SA, Shilatifard A, Amaral LAN, Perlman H, Sznajder JI, Argento AC, Gillespie CT, Dematte J, Jain M, Singer BD, Ridge KM, Lam AP, Bharat A, Bhorade SM, Gottardi CJ, Budinger G, Misharin AV. 2019. Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis. Am J Respir Crit Care Med 199:1517–1536. doi:10.1164/rccm.201712-2410OC. - DOI - PMC - PubMed

[4] Reyfman PA, Walter JM, Joshi N, Anekalla KR, McQuattie-Pimentel AC, Chiu S, Fernandez R, Akbarpour M, Chen C-I, Ren Z, Verma R, Abdala-Valencia H, Nam K, Chi M, Han S, Gonzalez-Gonzalez FJ, Soberanes S, Watanabe S, Williams KJN, Flozak AS, Nicholson TT, Morgan VK, Winter DR, Hinchcliff M, Hrusch CL, Guzy RD, Bonham CA, Sperling AI, Bag R, Hamanaka RB, Mutlu GM, Yeldandi AV, Marshall SA, Shilatifard A, Amaral LAN, Perlman H, Sznajder JI, Argento AC, Gillespie CT, Dematte J, Jain M, Singer BD, Ridge KM, Lam AP, Bharat A, Bhorade SM, Gottardi CJ, Budinger G, Misharin AV. 2019. Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis. Am J Respir Crit Care Med 199:1517–1536. doi:10.1164/rccm.201712-2410OC. - DOI - PMC - PubMed

[5] Subramanian A, Narayan R, Corsello SM, Peck DD, Natoli TE, Lu X, Gould J, Davis JF, Tubelli AA, Asiedu JK, Lahr DL, Hirschman JE, Liu Z, Donahue M, Julian B, Khan M, Wadden D, Smith IC, Lam D, Liberzon A, Toder C, Bagul M, Orzechowski M, Enache OM, Piccioni F, Johnson SA, Lyons NJ, Berger AH, Shamji AF, Brooks AN, Vrcic A, Flynn C, Rosains J, Takeda DY, Hu R, Davison D, Lamb J, Ardlie K, Hogstrom L, Greenside P, Gray NS, Clemons PA, Silver S, Wu X, Zhao W-N, Read-Button W, Wu X, Haggarty SJ, Ronco LV, Boehm JS, Schreiber SL, Doench JG, Bittker JA, Root DE, Wong B, Golub TR. 2017. A next generation connectivity map: L1000 platform and the first 1,000,000 profiles. Cell 171:1437–1452.e17. doi:10.1016/j.cell.2017.10.049. - DOI - PMC - PubMed

[6] Subramanian A, Narayan R, Corsello SM, Peck DD, Natoli TE, Lu X, Gould J, Davis JF, Tubelli AA, Asiedu JK, Lahr DL, Hirschman JE, Liu Z, Donahue M, Julian B, Khan M, Wadden D, Smith IC, Lam D, Liberzon A, Toder C, Bagul M, Orzechowski M, Enache OM, Piccioni F, Johnson SA, Lyons NJ, Berger AH, Shamji AF, Brooks AN, Vrcic A, Flynn C, Rosains J, Takeda DY, Hu R, Davison D, Lamb J, Ardlie K, Hogstrom L, Greenside P, Gray NS, Clemons PA, Silver S, Wu X, Zhao W-N, Read-Button W, Wu X, Haggarty SJ, Ronco LV, Boehm JS, Schreiber SL, Doench JG, Bittker JA, Root DE, Wong B, Golub TR. 2017. A next generation connectivity map: L1000 platform and the first 1,000,000 profiles. Cell 171:1437–1452.e17. doi:10.1016/j.cell.2017.10.049. - DOI - PMC - PubMed

[7] Mourad J-J, Levy BI. 30 March 2020. Interaction between RAAS inhibitors and ACE2 in the context of COVID-19. Nat Rev Cardiol doi:10.1038/s41569-020-0368-x. - DOI - PMC - PubMed

[8] Mourad J-J, Levy BI. 30 March 2020. Interaction between RAAS inhibitors and ACE2 in the context of COVID-19. Nat Rev Cardiol doi:10.1038/s41569-020-0368-x. - DOI - PMC - PubMed

[9] Perry CM, Balfour JA. 1996. Didanosine. Drugs 52:928–962. doi:10.2165/00003495-199652060-00014. - DOI - PubMed

[10] Perry CM, Balfour JA. 1996. Didanosine. Drugs 52:928–962. doi:10.2165/00003495-199652060-00014. - DOI - PubMed

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Repurposing Didanosine as a Potential Treatment for COVID-19 Using Single-Cell RNA Sequencing Data

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Repurposing Didanosine as a Potential Treatment for COVID-19 Using Single-Cell RNA Sequencing Data

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