SignificanceFavipiravir is a broad-spectrum antiviral that has shown promise in treatment of influenza virus infections, in particular due to the apparent lack of emergence of resistance mutations against the drug in cell culture or animal studies. We demonstrate here that a mutation in a conserved region of the viral RNA polymerase confers resistance to favipiravir in vitro and in cell culture. The resistance mutation has a cost to viral fitness, but this can be restored by a compensatory mutation in the polymerase. Our findings support the development of favipiravir-resistance diagnostic and surveillance testing strategies and reinforce the importance of considering combinations of therapies to treat influenza infections.

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A prototype dichotomous virtual impactor (DVI) using a single acceleration nozzle, operating at approximately 500 Il/min, and having an aerodynamic particle cutpoint diameter of about 2-3 pm has been constructed and tested. Under these conditions the flow through the acceleration nozrle is calculated to be turbulent. This sampler wa5 calibrated with a monodisperse aerosol, and the measured particle size-dependent collection efficiencies demonstrate that the sampler size fractionates atmospheric particulate matter as efficiently as the low-volume dichotomous virtual impactors. Analysis of tert data indicates that the high-volume sampler can be described by classical impaction theory. These data also indicate that over the range of Reynolds numbers from 24,000 to 81,000 there is little, if any, dependence of inferred acceleration nozzle turbulence on the performance characteristics of the sampling system. A comparison of the concentration of atmospheric particulate matter, sulfate, and calcium on the fine filter samples collected with colocated high-and low-volume virtual impactors also shows that the two samplers nre operating with similar performance characteristics. Additionally, the high-volume DVI collects at least 10-30 times the mass of particulate matter that the presently available virtual impactors collect and thus allows one to obtain improved precision in the measurement of those airborne species that are near the minimum detectable level of current analytical methods.Cunningham's slip correction factor (dimensionless) diameter of the collection probe (cm) diameter of the acceleration nozzle (cm) diameter of the particle (cm) diameter of the particle at 50% collection efficiency (cm) large particle air flow transport ratio (%) nozzle-to-probe spacing (cm) total flow rate (l/min) Reynolds number calculated for the acceleration nozzle (dimensionless) Stokes number (dimensionless) throat length of the acceleration nozzle (cm)