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Resistance to antiviral drugs for influenza is an ongoing public health concern. The neuraminidase (NA) inhibitor oseltamivir is the most prescribed antiviral drug for controlling influenza. However, during 2007-2009, oseltamivir-resistant [...]

Influenza viruses are classified into 4 types: A, B, C, and D (1). Influenza A viruses infect a wide range of species and pose threats to human and animal health. [...]

In this work, with a change in the time of mechanical processing in a high-energy planetary mill, composite particles were obtained from a mixture of titanium powders (grade PTS – 1) and titanium nitride powder in the size range from 10 to 100 μm. It was shown that ultrafine refractory particles of titanium nitride are uniformly distributed over the volume of agglomerates. It is assumed that the spraying of the composite powder by the method of cold or thermal spraying will increase the homogeneity of the distribution of refractory inclusions in the coating. The structure and morphology of the composite particle surface were studied, their X-ray diffraction patterns were obtained, and elemental analysis was carried out. It was found that during mechanical processing of the material, titanium nitride particles act as a surfactant and prevent the growth of agglomerates. It was shown that after 3 minutes of mechanical processing of the powder mixture, titanium nitride is uniformly distributed throughout the entire volume of the composite particle.

Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in the polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold) but also on in vitro replicative fitness. Although I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, control viruses outcompeted those carrying I38M or I38T substitutions, although their advantage was limited. These findings offer insights into the attributes of baloxavir-resistant viruses needed for informed risk assessment. [ABSTRACT FROM AUTHOR]

Baloxavir showed broad-spectrum in vitro replication inhibition of 4 types of influenza viruses (90% effective concentration range 1.2-98.3 nmol/L); susceptibility pattern was influenza A ˃ B ˃ C ˃ D. This drug also inhibited influenza A viruses of avian and swine origin, including viruses that have pandemic potential and those resistant to neuraminidase inhibitors. [ABSTRACT FROM AUTHOR]

Baloxavir showed broad-spectrum in vitro replication inhibition of 4 types of influenza viruses (90% effective concentration range 1.2-98.3 nmol/L); susceptibility pattern was influenza A ˃ B ˃ C ˃ D. This drug also inhibited influenza A viruses of avian and swine origin, including viruses that have pandemic potential and those resistant to neuraminidase inhibitors. [ABSTRACT FROM AUTHOR]

Since 2013, a total of 167 human infections with swine-origin (variant) influenza A viruses of A(H1N1)v, A(H1N2)v, and A(H3N2)v subtypes have been reported in the United States. Analysis of 147 genome sequences revealed that nearly all had S31N substitution, an M2 channel blocker-resistance marker, whereas neuraminidase inhibitor-resistance markers were not found. Two viruses had a polymerase acidic substitution (I38M or E199G) associated with decreased susceptibility to baloxavir, an inhibitor of viral cap-dependent endonuclease (CEN). Using phenotypic assays, we established subtype-specific susceptibility baselines for neuraminidase and CEN inhibitors. When compared with either baseline or CEN-sequence-matched controls, only the I38M substitution decreased baloxavir susceptibility, by 27-fold. Human monoclonal antibodies FI6v3 and CR9114 targeting the hemagglutinin's stem showed variable (0.03 to >10 µg/mL) neutralizing activity toward variant viruses, even within the same clade. Methodology and interpretation of laboratory data described in this study provide information for risk assessment and decision-making on therapeutic control measures.

Antiviral susceptibility of influenza viruses was assessed using a high-content imaging-based neutralization test. Cap-dependent endonuclease inhibitors, baloxavir and AV5116, were superior to AV5115 against type A viruses, and AV5116 was most effective against PA mutants tested. However, these three inhibitors displayed comparable activity (EC 50 8-22 nM) against type C viruses from six lineages. Banana lectin and a monoclonal antibody, YA3, targeting the hemagglutinin-esterase protein effectively neutralized some, but not all, type C viruses., Competing Interests: Andrei A. Ivashchenko and Alexandre V. Ivachtchenko are the cofounders of ChemDiv, managing members of AVISA LCC. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.