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.
Highlights
The outbreak of SARS-CoV-2 started in 2019, and extended to multiple continents within a month, which has been declared to be a public health emergency of international concern by the World Health Organization
By uploading the query files of the the differentially expressed genes (DEGs) and the genes co-expressed with angiotensin-converting enzyme 2 (ACE2) in lung, we identified several candidate drugs for the treatment of COVID-19
The DEGs of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) of patients with COVID-19 were sourced from the previous study of Yong X et al.1 (Supplementary File 1)
Summary
The outbreak of SARS-CoV-2 started in 2019, and extended to multiple continents within a month, which has been declared to be a public health emergency of international concern by the World Health Organization. COVID-19 manifests with fever, nonproductive cough, dyspnea, myalgia, fatigue, normal or decreased leukocyte counts, and severe lung injury (Wu et al, 2020). Severe and lethal cases showed organ dysfunction, including shock, acute respiratory distress syndrome (ARDS), acute cardiac injury, acute kidney injury, liver dysfunction and secondary inflammation (Chen et al, 2020; Huang et al, 2020; Wang et al, 2020; Wei-jie Guan, 2020). The coronavirus disease 2019 (COVID-19) has become a worldwide public health crisis. 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. We used the Connectivity map (Cmap) database to search for candidate drugs using transcriptome profiles of patients with COVID-19
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