Abstract
COVID-19 is a global pandemic impacting the daily living of millions. As variants of the virus evolve, a complete comprehension of the disease and drug targets becomes a decisive duty. The Omicron variant, for example, has a notably high transmission rate verified in 155 countries. We performed integrative transcriptomic and network analyses to identify drug targets and diagnostic biomarkers and repurpose FDA-approved drugs for SARS-CoV-2. Upon the enrichment of 464 differentially expressed genes, pathways regulating the host cell cycle were significant. Regulatory and interaction networks featured hsa-mir-93-5p and hsa-mir-17-5p as blood biomarkers while hsa-mir-15b-5p as an antiviral agent. MYB, RRM2, ERG, CENPF, CIT, and TOP2A are potential drug targets for treatment. HMOX1 is suggested as a prognostic biomarker. Enhancing HMOX1 expression by neem plant extract might be a therapeutic alternative. We constructed a drug-gene network for FDA-approved drugs to be repurposed against the infection. The key drugs retrieved were members of anthracyclines, mitotic inhibitors, anti-tumor antibiotics, and CDK1 inhibitors. Additionally, hydroxyquinone and digitoxin are potent TOP2A inhibitors. Hydroxyurea, cytarabine, gemcitabine, sotalol, and amiodarone can also be redirected against COVID-19. The analysis enforced the repositioning of fluorouracil and doxorubicin, especially that they have multiple drug targets, hence less probability of resistance.
【초록키워드】 COVID-19, Treatment, SARS-CoV-2, Biomarker, Antiviral, variant, Infection, Antibiotics, drug, omicron, FDA-approved drugs, virus, inhibitors, variants, cell cycle, global pandemic, Probability, therapeutic, pathway, drug target, repositioning, Omicron variant, targets, gemcitabine, antiviral agent, expression, Amiodarone, Differentially expressed genes, prognostic biomarker, Blood, Diagnostic biomarkers, Interaction, HMOX1, Analysis, Pathways, hydroxyurea, host cell, Doxorubicin, FLUOROURACIL, cytarabine, sotalol, digitoxin, FDA-approved drug, enrichment, daily living, transmission rate, Complete, transcriptomic, diagnostic biomarker, anthracyclines, CDK1, CENPF, mir-93, RRM2, TOP2A, identify, performed, example, the disease, less, suggested, analysis, Enhancing, mitotic, CIT, ERG, MYB, retrieved, 【제목키워드】 SARS-CoV-2, drugs, targets, Analysis, viral-host interaction,