Infections with respiratory viruses constitute a huge burden on our health and economy. Antivirals against some respiratory viruses are available, but further options are urgently needed. Enisamium iodide (laboratory code FAV00A, trade name Amizon®) is an antiviral marketed in countries of the Commonwealth of Independent States for the treatment of viral respiratory infections, but its clinical efficacy and mode of action are not well understood. Here, we investigated the efficacy of enisamium in patients aged between 18-60 years with confirmed influenza and other viral respiratory infections. Enisamium treatment resulted in reduced influenza virus shedding (at day 3, 71.2% in enisamium group tested negative versus 25.0% in placebo group, p < 0.0001), faster patient recovery (at day 14, 93.9% in enisamium group had recovered versus 32.5% in placebo group, p < 0.0001), and reduced disease symptoms compared to placebo (from 9.6 ± 0.7 to 4.6 ± 0.9 score points in enisamium group versus 9.7 ± 1.1 to 5.6 ± 1.1 score points in placebo group, p < 0.0001). Using mass-spectrometry, and cell-based and cell-free viral RNA synthesis assays, we identified a hydroxylated metabolite of enisamium, VR17-04. VR17-04 is capable of inhibiting influenza virus RNA synthesis and present in plasma of patients treated with enisamium. VR17-04 inhibits the activity of the influenza virus RNA polymerase more potently than its parent compound. Overall, these results suggest that enisamium is metabolized in humans to an inhibitor of the influenza virus RNA polymerase that reduces viral shedding and improves patient recovery in influenza patients.

Background: The use of recombinant human follicle-stimulating hormone (r-hFSH) in ovarian stimulation protocols for infertility treatment in assisted reproductive technology (ART) clinical practice is well established. More recent advancements include the availability of biosimilar r-hFSH products, which expand the choices available to healthcare practitioners and patients. Better understanding of how such a product contributes to routine clinical practice is valuable to help prescribers make informed treatment choices. The objective of this study was to examine the effectiveness and safety of ovarian stimulation (OS) with follitropin alfa (Ovaleap®) for routine IVF or intracytoplasmic sperm injection treatment in gonadotropin-releasing hormone (GnRH) antagonist cycles in real-world ART clinical practice.Methods: This non-interventional, multicenter, prospective study was initiated in 34 specialized reproductive medicine centers in Germany. Eligible women were 18-40 years old with a body mass index < 30 kg/m 2 , menstrual cycle 24-35 days and anti-Müllerian hormone ≥1 ng/mL, who were undergoing a first OS cycle exclusively with Ovaleap® during routine ART using a GnRH antagonist protocol. Primary effectiveness outcomes were number of retrieved oocytes after OS and clinical pregnancy rate (CPR). Secondary outcomes included fertilization rate, number of transferred embryos, live birth delivery rate, safety, and user satisfaction with the Ovaleap® pen.

Infections with respiratory viruses constitute a huge burden on our health and economy. Antivirals against some respiratory viruses are available, but further options are urgently needed. Enisamium iodide (laboratory code FAV00A, trade name Amizon®) is an antiviral marketed in countries of the Commonwealth of Independent States for the treatment of viral respiratory infections, but its clinical efficacy and mode of action are not well understood. Here, we investigated the efficacy of FAV00A in patients aged between 18-60 years with confirmed influenza and other viral respiratory infections. FAV00A treatment resulted in reduced influenza virus shedding (at day 3, 71.2% in FAV00A group tested negative versus 25.0% in placebo group, p < 0.0001), faster patient recovery (at day 14, 93.9% in FAV00A group had recovered versus 32.5 % in placebo group, p < 0.0001), and reduced disease symptoms compared to placebo (from 9.6 ± 0.7 to 4.6 ± 0.9 score points in FAV00A group versus 9.7 ± 1.1 to 5.6 ± 1.1 score points in placebo group, p < 0.0001). Using mass-spectrometry, and cell-based and cell-free viral RNA synthesis assays, we identified a hydroxylated metabolite of FAV00A, VR17-04. VR17-04 is capable of inhibiting influenza virus RNA synthesis and present in plasma of patients treated with FAV00A. VR-17-04 inhibits the activity of the influenza virus RNA polymerase more potently than its parent compound. Overall, these results suggest that FAV00A is metabolized in humans to an inhibitor of the influenza virus RNA polymerase that reduces viral shedding and improves patient recovery in influenza patients.Clinical data are available on ClincalTrials.gov under NCT04682444.