The present study assesses copper metabolism of the host organism as a target of antiviral strategy, basing on the “virocell” concept. Silver nanoparticles (AgNPs) were used as a specific active agent because they reduce the level of holo-ceruloplasmin, the main extracellular cuproenzyme. The mouse model of influenza virus A infection was used with two doses: 1 LD₅₀ and 10 LD₅₀. Three treatment regimens were used: Scheme 1—mice were pretreated 4 days before infection and then every day during infection development; Scheme 2—mice were pretreated four days before infection and on the day of virus infection; Scheme 3—virus infection and AgNP treatment started simultaneously, and mice were injected with AgNPs until the end of the experiment. The mice treated by Scheme 1 demonstrated significantly lower mortality, the protection index reached 60–70% at the end of the experiment, and mean lifespan was prolonged. In addition, the treatment of the animals with AgNPs resulted in normalization of the weight dynamics. Despite the amelioration of the infection, AgNP treatment did not influence influenza virus replication. The possibility of using nanosilver as an effective indirectly-acting antiviral drug is discussed.

The influenza virus continually evolves because of the high mutation rate, resulting in dramatic changes in its pathogenicity and other biological properties. This study aimed to evaluate the evolution of certain essential properties, understand the connections between them, and find the molecular basis for the manifestation of these properties. To that end, 21 A(H1N1)pdm09 influenza viruses were tested for their pathogenicity and toxicity in a mouse model with a ts/non-ts phenotype manifestation and HA thermal stability. The results demonstrated that, for a strain to have high pathogenicity, it must express a toxic effect, have a non-ts phenotype, and have a thermally stable HA. The ancestor A/California/07/2009 (H1N1)pdm influenza virus expressed the non-ts phenotype, after which the cycling trend of the ts/non-ts phenotype was observed in new strains of A(H1N1)pdm09 influenza viruses, indicating that the ratio of the ts phenotype will increase in the coming years. Of the 21 tested viruses, A/South Africa/3626/2013 had the high pathogenicity in the mouse model. Sequence alignment analysis showed that this virus has three unique mutations in the polymerase complex, two of which are in the PB2 gene and one that is in the PB1 gene. Further study of these mutations might explain the distinguishing pathogenicity.

The number of lung-adapted influenza viruses is limited. Most of them are not antigenically related to current circulating viruses. Viruses similar to recent strains are required for screening modern antiviral compounds and studying new vaccine candidates against novel influenza viruses. The process by which an influenza virus adapts to a new host is rather difficult. The aim of this study was to select a non-adapted current virus whose major biological properties correspond to those of classical lab-adapted viruses. Mice were inoculated intranasally with non-lung-adapted influenza viruses of subtype H1N1pdm09. They were monitored closely for body weight loss, mortality outcomes and gross pathology for 14 days following inoculation, as well as viral replication in lung tissue. Lung-adapted PR8 virus was used as a control. The tested viruses multiplied equally well in the lower respiratory tract of mice without prior adaptation but dramatically differed in lethality; the differences in their toxicity and pathogenicity in mice were established. A/South Africa/3626/2013 (H1N1)pdm09 virus was found to be an appropriate candidate to replace PR8 as a model virus for influenza research. No prior adaptation to the animal model is needed to reach the pathogenicity level of the classical mouse-adapted PR8 virus.

A wide diversity of zoonotic viruses that are capable of overcoming host range barriers facilitate the emergence of new potentially pandemic viruses in the human population. When faced with a new virus that is rapidly emerging in the human population, we have a limited knowledge base to work with. The pandemic invasion of the new SARS-CoV-2 virus in 2019 provided a unique possibility to quickly learn more about the pathogenesis of respiratory viruses. In this review, the impact of pandemics on the circulation of seasonal respiratory viruses is considered. The emergence of novel respiratory viruses has often been accompanied by the disappearance of existing circulating strains. Some issues arising from the spread of pandemic viruses and underlying the choices of a strategy to fight the coronavirus infection are discussed.

Silver nanoparticles (AgNPs) of various sizes and shapes are widely used because of their antibacterial properties. However, their bioactivity in mammals is insufficiently investigated. The aim of the present study was to assess the effect of AgNPs' shape on their antibacterial activity, cytotoxicity, and ability to interfere in copper metabolism in mice. For this, AgNPs with the same linear size (75 nm), but different shape (spherical and quasi-spherical), were fabricated by chemical reduction from silver nitrate. The test of the biological activity of AgNPs showed that both types of particles suppressed bacterial (E. coli) and mammalian (A549) cell growth in a time- and dose-dependent manner. Quasi-spherical AgNPs had stronger antibacterial activity (several orders of magnitude) than the spherical AgNPs. In mice, the intake, distribution and accumulation of silver from AgNPs depending on the administration method were compared and intraperitoneal injections were chosen as the most appropriate. Silver concentration in organs of mice and its distribution in the organs did not depend on the shape of AgNPs. During the 7 days of intraperitoneal treatment with AgNPs, the silver concentration in blood serum increased, while the copper concentration and ceruloplasmin (Cp) oxidase activity (measured by the o-dianisidine in-gel assay) decreased. At the same time, the Cp protein concentration determined by immunoblotting did not change. Analysis of the blood serum by gel-filtration has shown that blood serum silver was associated with Cp and with a larger protein, presumably α-2-macroglobulin. After the AgNP injections were cancelled, the organs and the blood serum were cleared from silver through bile, while the copper concentration and Cp oxidase activity of blood serum recovered to their normal levels. So, the correlation between particle shape and their biological activity was observed. Quasi-spherical AgNPs having more edges possessed higher antibacterial activity. At the same time, both types of AgNPs lowered the copper status of blood serum in mice in a similar manner. In the article, the potential danger of AgNP's low doses for mammals, including humans, and the specificity of the nanosilver turnover in the mammalian body, which suggests that AgNPs can be used for safe treatment, are discussed.