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PMC:7890668 / 5316-6422
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7890668","sourcedb":"PMC","sourceid":"7890668","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7890668","text":"Executing this query generated 47 subgraphs ranked by an algorithm implemented in ROBOKOP (Morton et al., 2019), with the pathway serving as a rationale for the linagliptin clinical trial against COVID-19 (Linagliptin-T2D-DPP4-COVID-19; Fig. 1B) ranked the highest. Three conditions—pneumonia, T2D and hypertensive disorder—were identified as associated with COVID-19. Genes associated with these conditions and also linked to linagliptin are annotated in Figure 1B. Pneumonia was not directly related to any of these genes except for transforming growth factor beta (TGFβ-1), the inhibition of which results in increased susceptibility to pneumonia in mice with a pneumonia-resistant phenotype (Neill et al., 2012). Relatedly, linagliptin has been reported to ‘significantly decrease’ TGFβ-1 transcript levels (Wang et al., 2015). Our answer graph suggests that linagliptin may inhibit TGFβ-1 transcription and thus possibly increase patients’ risk of developing more severe pneumonia, even though it may alleviate some of the more severe pathologies of COVID-19 seen in T2D patients via DPP-4 inhibition.","tracks":[]}