ArticleFrontiers in genetics2020
Underlying Mechanisms and Candidate Drugs for COVID-19 Based on the Connectivity Map Database.
Article in Frontiers in genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 21 citations in OpenAlex.
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- Machine learning and network medicine approaches for drug repositioning for COVID-19.Patterns (New York, N.Y.) · 2022Article
- Strategies to identify candidate repurposable drugs: COVID-19 treatment as a case example.Translational psychiatry · 2021Review
- Potential for the Repurposing of Adamantane Antivirals for COVID-19.Drugs in R&D · 2021Review
- Identification of 37 Heterogeneous Drug Candidates for Treatment of COVID-19 via a Rational Transcriptomics-Based Drug Repurposing Approach.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Co-crystallization and structure determination: An effective direction for anti-SARS-CoV-2 drug discovery.Computational and structural biotechnology journal · 2021Review
- All-cause mortality among patients treated with repurposed antivirals and antibiotics for COVID-19 in Mexico City: A real-world observational study.EXCLI journal · 2021Article
- Gaining insights on immune responses to the novel coronavirus, COVID-19 and therapeutic challenges.Life sciences · 2020Article
- Investigating the human protein-host protein interactome of SARS-CoV-2 infection in the small intestine.Gastroenterology and hepatology from bed to bench · 2020Article
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2 authors at 1 institution in 1 country.
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Abstract
backgroundThe coronavirus disease 2019 (COVID-19) has become a worldwide public health crisis. At present, there are no effective antiviral drugs to treat COVID-19. Although some vaccines have been developed, late-stage clinical trials that allow licensure by regulatory agencies are still needed. Previous reports have indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV are highly homologous and both use angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells, and SARS-CoV infection reduces the ACE2 expression in the lung. Therefore, the analysis of genes co-expressed with ACE2 in the lung may uncover the underlying mechanism of COVID-19. Finally, we used the Connectivity map (Cmap) database to search for candidate drugs using transcriptome profiles of patients with COVID-19.
methodBased on the differentially expressed genes (DEGs), indicated by the expression of RNAs isolated from bronchoalveolar lavage fluid (BALF) cells of patients with COVID-19, we performed functional enrichment analysis and hub gene cluster analysis. Furthermore, we identified genes co-expressed with ACE2 in healthy lung samples and analyzed the significant genes. Additionally, to identify several candidate drugs for the treatment of COVID-19, we queried Cmap using DEGs and genes co-expressed with ACE2. RESULTS AND
conclusionThe up-regulated genes in the BALF cells of patients with COVID-19 are related to viral mRNA translation. The down-regulated genes are related to immune response functions. Genes positively correlated with ACE2 are related to immune defense and those negatively correlated are enriched in synaptic transmission functions. The results reflected prosperous viral proliferation and immune dysfunction in patients. Furthermore, ACE2 may not only mediate viral entrance, but also play an important role in immune defense. By using Cmap with transcriptome profiles of patients with COVID-19, we identified candidate drugs for the treatment of COVID-19, such as amantadine and acyclovir.
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