T-705-Derived Prodrugs Show High Antiviral Efficacies against a Broad Range of Influenza A Viruses with Synergistic Effects When Combined with Oseltamivir.

Emerging influenza A viruses (IAV) bear the potential to cause pandemics with unpredictable consequences for global human health. In particular, the WHO has declared avian H5 and H7 subtypes as high-risk candidates, and continuous surveillance of these viruses as well as the development of novel, broadly acting antivirals, are key for pandemic preparedness. In this study, we sought to design T-705 (Favipiravir) related inhibitors that target the RNA-dependent RNA polymerase and evaluate their antiviral efficacies against a broad range of IAVs.

Transcatheter Aortic Valve Replacement for Severe Aortic Valve Stenosis: Do Patients Experience Better Quality of Life Regardless of Gradient?

Background: Aortic valve replacement improves survival for patients with low-gradient aortic valve stenosis, but there is a paucity of data on postoperative quality of life for this population.

Methods: In a single-center retrospective analysis of 304 patients with severe aortic valve stenosis who underwent transcatheter aortic valve replacement, patients were divided into 4 groups based on mean pressure gradient, left ventricular ejection fraction, and stroke volume index. Using the Kansas City Cardiomyopathy Questionnaire-12, quality of life was assessed immediately before and 1 month after transcatheter aortic valve replacement.

Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106.

The antiviral pseudo-base T705 and its de-fluoro analog T1106 mimic adenine or guanine and can be competitively incorporated into nascent RNA by viral RNA-dependent RNA polymerases. Although dispersed, single pseudo-base incorporation is mutagenic, consecutive incorporation causes polymerase stalling and chain termination. Using a template encoding single and then consecutive T1106 incorporation four nucleotides later, we obtained a cryogenic electron microscopy structure of stalled influenza A/H7N9 polymerase.

Impact of frailty on mortality and quality of life in patients with a history of cancer undergoing transcatheter aortic valve replacement.

Background: Transcatheter aortic valve replacement (TAVR) is increasingly offered for aortic stenosis (AS) treatment in patients with a history of cancer. The impact of frailty on outcomes in this specific patient population is not well described.

Hypothesis: Frailty is associated with mortality and poorer quality of life (QOL) outcomes in patients undergoing TAVR with a history of cancer.

Targeting viral genome synthesis as broad-spectrum approach against RNA virus infections.

Zoonotic spillover, i.e. pathogen transmission from animal to human, has repeatedly introduced RNA viruses into the human population.