De Meyer, S. | Search bioRxiv

bioRxiv2020

In Vitro Activity of Itraconazole Against SARS-CoV-2

BackgroundAs long as there is no vaccine available, having access to inhibitors of SARS-CoV-2 will be of utmost importance. Antivirals against coronaviruses do not exist, hence global drug re-purposing efforts have been carried out to identify agents that may provide clinical benefit to patients with COVID-19. Itraconazole, an antifungal agent, has been reported to have potential activity against animal coronaviruses. MethodsUsing cell-based phenotypic assays, the in vitro antiviral activity of itraconazole and 17-OH itraconazole was assessed against clinical isolates from a German and Belgian patient infected with SARS-CoV-2. ResultsItraconazole demonstrated antiviral activity in human Caco-2 cells (EC50 = 2.3 M; MTT assay). Similarly, its primary metabolite, 17-OH itraconazole, showed inhibition of SARS-CoV-2 activity (EC50 = 3.6 M). Remdesivir inhibited viral replication with an EC50 = 0.4 M. Itraconazole and 17-OH itraconazole resulted in a viral yield reduction in vitro of approximately 2-log10 and approximately 1-log10, as measured in both Caco-2 cells and VeroE6-eGFP cells, respectively. The viral yield reduction brought about by remdesivir or GS-441524 (parent nucleoside of the antiviral prodrug remdesivir; positive control) was more pronounced, with an approximately 3 log10 drop and >4 log10 drop in Caco-2 cells and VeroE6-eGFP cells, respectively. DiscussionItraconazole and 17-OH itraconazole exert in vitro low micromolar activity against SARS-CoV-2. Despite the in vitro antiviral activity, itraconazole did not result in a beneficial effect in hospitalized COVID-19 patients in a clinical study (EudraCT Number: 2020-001243-15). HighlightsO_LIItraconazole exerted in vitro low micromolar activity against SARS-CoV-2 (EC50 = 2.3 M) C_LIO_LIRemdesivir demonstrated potent antiviral activity, confirming validity of the assay C_LIO_LIItraconazole has since shown no efficacy in a clinical study in hospitalized COVID-19 patients C_LI

pharmacology and toxicology↗

bioRxiv2020

Using single-plant -omics in the field to link maize genes to functions and phenotypes

Most of our current knowledge on plant molecular biology is based on experiments in controlled lab environments. Over the years, lab experiments have generated substantial insights in the molecular wiring of plant developmental processes, stress responses and phenotypes. However, translating these insights from the lab to the field is often not straightforward, in part because field growth conditions are very different from lab conditions. Here, we test a new experimental design to unravel the molecular wiring of plants and study gene-phenotype relationships directly in the field. We molecularly profiled a set of individual maize plants of the same inbred background grown in the same field, and used the resulting data to predict the phenotypes of individual plants and the function of maize genes. We show that the field transcriptomes of individual plants contain as much information on maize gene function as traditional lab-generated transcriptomes of pooled plant samples subject to controlled perturbations. Moreover, we show that field-generated transcriptome and metabolome data can be used to quantitatively predict at least some individual plant phenotypes. Our results show that profiling individual plants in the field is a promising experimental design that could help narrow the lab-field gap.

systems biology↗