Two biological types of influenza virus are known and distinguished by the structure of the surface glycoprotein, hemagglutinin (HA). The noninfectious virions contain the uncleaved HA0 (80 kDa), whereas the infectious type have a cleaved form of two subunits, HA1 (55 kDa) and HA2 (25 kDa). The point cleavage of HA0→HA1+HA2 by host proteases regulates the virion integrity to maintain the functionality of the intravirion axis HA→M2→M1→RNP. The HA0 containing virions are more resistant than the HA1/HA2 virions to the 75 °C temperature used in pasteurizing milk and foods. The noninfectious HA0 virions treated at 75 °C were able to retain infectious potential, which was activated by trypsin; in contrast, the infectious HA1/HA2 virions lost infectivity irreversibly under pasteurization. The data suggest that (i) influenza viruses retain their infectious potential in the external environment by means of noninfectious virions containing the uncleaved HA0 and (ii) a stronger pasteurization regimen in terms of temperature and duration of thermal treatment is recommended to inactivate such potentially infectious virions in food products.
Influenza A virus has a wide natural areal among birds, mammals, and humans. One of the main regulatory adaptors of the virus host range is the major NP protein of the viral nucleocapsid. Phylogenetic analysis of the NP protein of different viruses has revealed the existence of two phylogenetic cohorts in human influenza virus population. Cohort I includes classical human viruses that caused epidemics in 1957, 1968, 1977. Cohort II includes the H1N1/2009pdm virus, which had a mixed avian–swine origin but caused global human pandemic. Also, the highly virulent H5N1 avian influenza virus emerged in 2021 and caused outbreaks of lethal infections in mammals including humans, appeared to have the NP gene of the second phylogenetic cohort and, therefore, by the type of adaptation to human is similar to the H1N1/2009pdm virus and seems to possess a high epidemic potential for humans. The data obtained shed light on pathways and dynamics of adaptation of avian influenza viruses to humans and propose phylogenetic algorithm for systemic monitoring of dangerous virus strains to predict epidemic harbingers and take immediate preventive measures.
A number of new conjugates of dehydroabiethylamine and adamantane was obtained using a three-step synthetic scheme in order to study the effect of linker type and length on biological activity. The inhibitory activity of the synthesized compounds toward the DNA repair enzyme Tyrosyl-DNA phosphodiesterase 1 was studied. The compounds are potent inhibitors, exhibiting activity in micromolar concentrations.
To date, various strategies have been proposed to increase the efficiency of cancer therapy. It is known that the action of DNA repair system can determine the resistance of cancer cells to DNA-damaging chemotherapy and radiotherapy, and one of these ways to increase therapeutic efficiency is the search for inhibitors of enzymes of the DNA repair system. Inhibition of the DNA repair enzyme tyrosyl-DNA phosphodiesterase1 (Tdp1) leads to an increase in the effectiveness of the topoisomerase 1 (Top1) inhibitor, the anticancer drug topotecan. Covalent complexes Top1-DNA, which are normally short-lived and are not a threat to the cell, are stabilized under the influence of topotecan and lead to cell death. Tdp1 eliminates such stabilized complexes and thus weaken the effect of topotecan therapy. We have previously shown that the use of the usnic acid hydrazonothiazole derivative OL9-119 in combination with topotecan increased the antitumor and antimetastatic efficacy of the latter in a mouse model of Lewis lung carcinoma. In this work, it was shown that the combined use of topotecan and Tdp1 inhibitor, the hydrazonothiazole derivative of usnic acid OL9-119 , leads to an increase in the DNA-damaging effect of topotecan which is used in the clinic for the treatment of cancer. The study of the proapoptotic effect of the compound OL9-119 showed that the compound itself does not induce apoptosis, but increases the proapoptotic effect of topotecan. The results of the study could be used to improve the effectiveness of anticancer therapy and/or to reduce the therapeutic dose of topotecan and, therefore, the severity of side effects.
The antiviral drug favipiravir (FVP), which is a structural analogue of guanosine, undergoes chemical transformation in infected cells by cellular enzymes into a nucleotide form — favipiravir ribose triphosphate (FVPRTP). FVP-RTP is able to bind to viral RNA-dependent RNA polymerase and integrate into the viral RNA chain, causing a significant mutagenic effect through G→A and С→U transitions in the viral RNA genome. Besides the virus inhibiting effect, the increased synthesis of mutant virions under the action of FPV possess a threat of the emergence of novel threatening viral strains with high pathogenicity for humans and animals and acquired resistance to chemotherapeutic compound. There are three ways to minimize this mutagenic effect of FP. (1) Synthesis of new FPV modifications lacking the ability to integrate into the synthesized viral RNA molecule. (2) The combined use of FPV with antiviral chemotherapeutic drugs of a different mechanism of action directed at various viral and/or host cell targets. (3) Permanent application of high therapeutic doses of FPV under the strict medical control to enhance the lethal mutagenic effect on an infectious virus in the recipient organism to prevent the multiplication of its mutant forms.
Solar and geomagnetic data demonstrate that, at the decay phase of solar activity in 2016, the dominating role in strong geomagnetic perturations was played by long-lived corotating regions of interaction between solar-wind streams with different velocities. The results of monitoring of interplanetary scintillations in time intervals preceding the arrival to the Earth of several corotating solar-wind perturbations observed in 2016 have been analyzed. The aim of the study is to determine the characteristic features of the dynamics of the scintillation level. The scintillations in the twilight sector weaken three to four days before the arrival of the compressed part of the perturbation at the Earth, which can be interpreted as a considerable decrease in the level of small-scale plasma turbulence in the extended region upstream of the frontal part of the perturbation. The arrival of the perturbation at the Earth is not always accompanied by a magnetic storm. Confident short-term geomagnetic activity forecasting requires additional data about the direction of the Bz magnetic field component in the perturbed stream. Monitoring of interplanetary scintillations shows that, simultaneous with the magnetic storm, second-timescale scintillations are enhanced, which are recorded most clearly if the storm takes place during twilight or night-time hours. In contrast to flare-driven perturbations, when the enhancement of night-time scintillations is due to the perturbed ionosphere, in the case of corotating perturbations, the accompanying scintillation enhancement is related to the interplanetary medium adjacent to the Earth, and is due to an increase in the absolute level of small-scale turbulence in the compressed part of the perturbation.
In the course of monitoring interplanetary scintillations of a large number of sources using the Big Scanning Antenna of the Lebedev Physical Institute, a search for pulsars with periods ≥0.4 s at declinations −9◦ < δ < 42◦ and right ascensions 0h < α < 24h was simultaneously carried out. The search was conducted using four years of observations carried out at 110.25MHz in six frequency channels making up a 2.5 MHz band and having a time resolution of 100 ms. The initial identification of pulsar candidates was done using Fourier power spectra averaged over the entire observational period; the pulsar candidates were then verified using observations with higher frequency and time resolution: 32 frequency channels and a time resolution of 12.5 ms. Eighteen new pulsars were discovered in the studied area, whose main characteristics are presented.