Multi-omics-based identification of SARS-CoV-2 infection biology and candidate drugs against COVID-19

Abstract

SARS-CoV-2 has ushered a global pandemic with no effective drug being available at present. Although several FDA-approved drugs are currently under clinical trials for drug repositioning, there is an on-going global effort for new drug identification. In this paper, using multi-omics (interactome, proteome, transcriptome, and bibliome) data and subsequent integrated analysis, we present the biological events associated with SARS-CoV-2 infection and identify several candidate drugs against this viral disease. We found that: (i) Interactome-based infection pathways differ from the other three omics-based profiles. (ii) Viral process, mRNA splicing, cytokine and interferon signaling, and ubiquitin mediated proteolysis are important pathways in SARS-CoV-2 infection. (iii) SARS-CoV-2 infection also shares pathways with Influenza A, Epstein-Barr virus, HTLV-I, Measles, and Hepatitis virus. (iv) Further, bacterial, parasitic, and protozoan infection pathways such as Tuberculosis, Malaria, and Leishmaniasis are also shared by this virus. (v) A total of 50 candidate drugs, including the prophylaxis agents and pathway specific inhibitors are identified against COVID-19. (vi) Betamethasone, Estrogen, Simvastatin, Hydrocortisone, Tositumomab, Cyclosporin A etc. are among the important drugs. (vii) Ozone, Nitric oxide, plasma components, and photosensitizer drugs are also identified as possible therapeutic candidates. (viii) Curcumin, Retinoic acids, Vitamin D, Arsenic, Copper, and Zinc may be the candidate prophylaxis agents. Nearly 70% of our identified agents are previously suggested to have anti-COVID-19 effects or under clinical trials. Among our identified drugs, the ones that are not yet tested, need validation with caution while an appropriate drug combination from these candidate drugs along with a SARS-CoV-2 specific antiviral agent is needed for effective COVID-19 management.

Keywords: COVID-19; Candidate drugs; Infection pathways; Interactome; Prophylaxis agents; Proteome; SARS-CoV-2; Transcriptome.

Graphical abstract

Fig. 1

The flow diagram of the overall strategy applied in this analysis. For details, see the methods section.

Fig. 2

Consolidated biological processes and pathways. (A) Biological processes enriched in at least 3 omics-based analyses. (B) Pathways enriched in at least 3 omics-based analyses. The X axis represents the number of appearances of the biological processes/pathways combining all of our omics-based analyses.

Fig. 3

Consolidated drugs and drug categories. (A) Top drugs enriched in at least 3 omics-based analyses. (B) Top drug categories with at least 2 drugs. The X axis represents the number of appearances of the drugs/drug categories combining all of our omics-based analyses.

Fig. 4

Consolidated drugs under the top ten drug categories. The X axis represents the number of appearances of the drugs under each category as per our combined all omics-based analyses.

Fig. 5

Consolidated drugs and drug categories by combining the five pathways. (A) Top drugs enriched in at least 3 omics-based analyses. (B) Top drug categories with at least 2 drugs. The X axis represents the number of appearances of the drugs/drug categories combining all of our omics-based analyses.

Fig. 6

Consolidated drugs under the top nine drug categories. The X axis represents the number of appearances of the drugs under each category as per our combined all omics-based analyses.