Spread Of Virus Infection Research Articles

Modeling the Spread of Viral Infection in a Local Atmosphere Infected with the SARS-CoV-2 Virus: Constant Virion Concentration

Modeling the Spread of Viral Infection in a Local Atmosphere Infected with the SARS-CoV-2 Virus: Constant Virion Concentration

Limitation of Human Rights and Freedoms amid New Global Challenges (Lessons from the Pandemic)

Globalization has had far-reaching effects on all key spheres of public life, leading to mixed outcomes, both positive and negative. One of the recent global trends is the fast and large-scale spread of viral infections, which has profoundly reshaped the economic landscapes, political environments, and government systems of most states. As the COVID-19 pandemic progressed, governments worldwide were forced to impose unprecedented restrictions that interfered with fundamental human rights, such as the freedom of movement and speech, to curb the virus spread. It sparked rigorous debate among the academic community and practicing lawyers. This article overviews the measures taken by Russia and other states in response to the COVID-19 pandemic. The obtained results highlight the need to legally establish new conceptual frameworks related to disease control, as well as to develop clear legal guidelines on optional and mandatory steps that public authorities should take in order to ensure the sanitary and epidemiological well-being of the population. Therefore, it was concluded that certain legal provisions must be specified to define the grounds and extent to which the rights and freedoms of citizens can be limited in case of viral epidemics.

Disruption of herpes simplex virus type 2 pUL21 phosphorylation impairs secondary envelopment of cytoplasmic nucleocapsids.

It is well known that post-translational modification of proteins by phosphorylation can regulate protein function. Here, we determined that phosphorylation of the multifunctional HSV-2 tegument protein pUL21 requires the viral serine/threonine kinase pUL13. In addition, we identified serine residues within HSV-2 pUL21 that can be phosphorylated. Phenotypic analysis of mutant HSV-2 strains with deficiencies in pUL21 phosphorylation revealed reductions in both cell-cell spread of virus infection and virus replication. Deficiencies in pUL21 phosphorylation also compromised the secondary envelopment of cytoplasmic nucleocapsids, a critical final step in the maturation of all herpes virions. Unlike HSV-2 pUL21, phosphorylation of HSV-1 pUL21 was not detected. This fundamental difference between HSV-2 and HSV-1 may underlie our previous observations that the requirements for pUL21 differ between HSV species.

Dendritic Cells Pulsed with HAM/TSP Exosomes Sensitize CD4 T Cells to Enhance HTLV-1 Infection, Induce Helper T-Cell Polarization, and Decrease Cytotoxic T-Cell Response.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive demyelinating disease of the spinal cord due to chronic inflammation. Hallmarks of disease pathology include dysfunctional anti-viral responses and the infiltration of HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ T cells in the central nervous system. HAM/TSP individuals exhibit CD4+ and CD8+ T cells with elevated co-expression of multiple inhibitory immune checkpoint proteins (ICPs), but ICP blockade strategies can only partially restore CD8+ T-cell effector function. Exosomes, small extracellular vesicles, can enhance the spread of viral infections and blunt anti-viral responses. Here, we evaluated the impact of exosomes isolated from HTLV-1-infected cells and HAM/TSP patient sera on dendritic cell (DC) and T-cell phenotypes and function. We observed that exosomes derived from HTLV-infected cell lines (OSP2) elicit proinflammatory cytokine responses in DCs, promote helper CD4+ T-cell polarization, and suppress CD8+ T-cell effector function. Furthermore, exosomes from individuals with HAM/TSP stimulate CD4+ T-cell polarization, marked by increased Th1 and regulatory T-cell differentiation. We conclude that exosomes in the setting of HAM/TSP are detrimental to DC and T-cell function and may contribute to the progression of pathology with HTLV-1 infection.

Efficient Green Solvent Extraction and Bioassay Studies of Favipiravir in Rat Dried Blood Spots Using Ionic Liquid-Based Dispersive Liquid-Liquid Microextraction (IL-DLLME) Coupled with HPLC-PDA: Application to Bioequivalence Studies

Background: Favipiravir is an antiviral drug having pyrazine group moiety. It is a reliable and an efficient green solvent, and a highly recoverable bio-sampling method is required for it. It is widely used in COVID-19 treatment for the prevention of the spread of viral infections in the body Objective: This proposed green solvent (ionic liquid)-based bioassay study aimed to quantify favipiravir in rat-dried blood spots using Dispersive Liquid-liquid Microextraction (IL-DLLME). Methods: The proposed bioassay separation was achieved through an isocratic elution mode using a hybrid silica-based ODS column (250 × 4.6 mm; 5 μm), a column temperature of 25°C, an injection volume of 10 μL, a flow rate of 1.0 mL/min, and a detector wavelength set at 310 nm. The run time was less than 10 minutes. Mobile phase was delivered with acetonitrile, methanol, and 10 mM Na2HPO4 at pH 4.0 ± 0.5, (15: 20: 65, v/v/v). In a microtube, 50 mL of Ionic Liquid (IL), 500 μL of disperser ACN, 50 μL of 10% NaCl, and IS (20 ng mL-1) were added to perform the Dried Blood Spot (DBS) sample extraction methodology. The advantages of the proposed methodology have been found to include minimum hematocrit effect and an adequate blood volume for testing, easy transportation, and significant extraction recovery. The sample analysis has been carried out using HPLC-PDA with oseltamivir used as an internal standard. Results: We have investigated the important variables, i.e., salt concentration (10% NaCl, analyte recovery being higher) and disperser solvent [50μL of BMIHP plus 500 μL of ACN (v/v) yielding the highest recovery], in the extraction process. Extraction Recovery (ER) and Enrichment Factor (EF) were also evaluated using the IL-DLLME method. The calibration curve examined a range of 0.5-150 μg/mL, with a lower Limit of Quantification (LOQ) being 0.5 μg/mL in QC as well as calibration samples, respectively. Conclusion: Significant bioanalytical validation has been performed and all the parameters have been evaluated systematically as per bioanalytical method validation protocols, i.e., US FDA- 2018 guidelines. The following analytical parameters have been covered: standard curve, limit of quantification, range, recovery, stability, accuracy, precision, sensitivity, ER, EF, and selectivity. The developed bioassay method has been successfully applied in the pharmacokinetic studies of rats and successfully applied in bulk drugs.

Oral microbiota autobacteriocins directed against pathogens of bacterial complications of respiratory infections

Recent years have been marked by a wide spread of respiratory viral infections, which are often accompanied by the development of bacterial complications. The greatest danger is posed by nosocomial strains with multidrug resistance. One of the ways to combat antibiotic-resistant strains is the possibility of using bacteriocins produced by certain bacteria that are present in the human body, food, and the environment. The most interesting are the strains of autobacteriocins isolated from the human's own normal microbiota, which does not have immune rejection. The purpose of the study: to investigate the antibacterial effect of autobacteriocins of the oral microbiota against the main pathogens of bacterial complications in respiratory infections. Six reference strains from the ESKAPE group (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) and 18 multi-resistant strains of the same group isolated from the respiratory tract of individuals with bacterial complications of viral infections were examined. The study used bacteriological, molecular biological, and statistical methods, as well as mass spectrometric research method. The autobacteriocins isolated from Enterococcus faecalis, Streptococcus salivarius, and Lactobacillus paracasei bacteria were the most effective against multidrug-resistant strains from the ESKAPE group. Notably, the concentration of bacteriocin-producing bacteria in the medium of co-cultivation was 500 and 1,000 times less than the strains against which they were directed. Suppression of the growth of multidrug-resistant strains by 2-3 times compared with the initial one was observed after 2 hours. Thus, the antibacterial effectiveness of autobacteriocins against resistant strains of bacteria isolated from the same individual suggests the possibility of a personalized approach to obtaining and using autoprobiotic strains of bacteria to combat bacterial complications of the respiratory tract.

Technology for Protecting Building Envelopes in Construction Using Magnetron Sputtering

The global environmental agenda is aimed at saving energy resources in all areas of human activity. An important condition for energy saving and increasing energy efficiency is the thermal protection of buildings and structures of all types. Currently, when designing and constructing buildings, structurally oriented solutions are needed to provide conditions for the implementation of modern innovative technologies. At the same time, when producing new thermal insulation (heat-protective) materials, it is necessary to take into account such important issues as environmental friendliness and ensuring a comfortable microclimate. Issues of indoor air exchange are extremely important, especially during the spread of new viral infections. Thermal insulation (thermal protection) of buildings must ensure air circulation, that is, be vapor permeable. Polyester material has this property. Modern technologies make it possible to impart heat-reflecting properties to such materials by applying metallized nanolayers or their compounds to their surface. Among the methods for applying such layers, a special place is occupied by the magnetron sputtering method, which is used in the technology of applying protective coatings to the surface of products made from roll and sheet materials. With the development of applied technological research in the chemical industry, many substances (compounds) were invented, some of which gained such popularity that they began to be used in the production of a huge number of materials, including in the construction industry. One of these substances was polyester as a high-molecular compound, which became widely used in many areas of industry. Polyester material is often combined with other man-made or natural fibers. Among them: cotton, linen, wool, polyamide. As a result, we obtain a canvas (materials) with new characteristics, adding new unique properties, such as strength and wear resistance, does not fade in the sun, and does not require special care. Polyester fabric is used for suspended ceilings and in building materials. Its high density of 250 kg per cubic meter allows this to be done. By combining the production of polyester and cotton, the material acquires the properties of breathability, hygroscopicity and low thermal conductivity. The purpose of this article is to describe the technology of the ion-plasma processing method of combined linen materials with possible application in the construction industry.

Repetition in social contacts: implications in modelling the transmission of respiratory infectious diseases in pre-pandemic and pandemic settings.

The spread of viral respiratory infections is intricately linked to human interactions, and this relationship can be characterized and modelled using social contact data. However, many analyses tend to overlook the recurrent nature of these contacts. To bridge this gap, we undertake the task of describing individuals' contact patterns over time by characterizing the interactions made with distinct individuals during a week. Moreover, we gauge the implications of this temporal reconstruction on disease transmission by juxtaposing it with the assumption of random mixing over time. This involves the development of an age-structured individual-based model, using social contact data from a pre-pandemic scenario (the POLYMOD study) and a pandemic setting (the Belgian CoMix study), respectively. We found that accounting for the frequency of contacts impacts the number of new, distinct, contacts, revealing a lower total count than a naive approach, where contact repetition is neglected. As a consequence, failing to account for the repetition of contacts can result in an underestimation of the transmission probability given a contact, potentially leading to inaccurate conclusions when using mathematical models for disease control. We, therefore, underscore the necessity of acknowledging contact repetition when formulating effective public health strategies.

Update on Monkeypox Virus Infection

The World Health Organization declared the 2022 Monkeypox outbreak as a Public Health Emergency of International Concern, reflecting the rapid spread of infections in non-endemic countries. Since 2022, more than 95,000 confirmed cases with 185 deaths were reported in at least 117 countries, most of them in Europe and USA. Gender-based studies documented preponderance in men (96.8%). Most of them were men who have sex with men (MSM) suggesting the sexual route as the main way of transmission. Mpox infection is usually transmitted by close contact through body fluids, and genital secretions. Exposure to infected respiratory droplets occurs after prolonged exposure. Indirect contact is less frequent. Incubation period is in average 12 days. Prodromal symptoms are systemic and nonspecific succeed with lymphadenopathy. Eruptive rash is changing from macules-papules-blisters-pustules to scabs. Diagnosis is based on clinical occurrence of typical skin and/or mucosal lesions, systemic symptoms, and potential contact to a Mpox-infected individual. The preferred diagnostic test is real-time or conventional polymerase chain reaction (PCR). Laboratory tests based on the detection of antigens or antibodies are not used due to serological cross-reactivity with other orthopoxviruses. The world health authorities agree that smallpox vaccines protect against Mpox infection due to the antigenic similarity between both viruses. New vaccine approved is MVA-BN which contain an attenuated form of vaccinia virus “Ankara” related to the smallpox virus. Antivirals are used to treat Mpox infection, namely cidofovir, tecovirimat and brincidofovir. Individual and universal protective measures should be used to prevent the spread of Mpox viral infection.

A multiplex RT-qPCR assay for simultaneous detection of cucurbit viruses from individual whitefly and plant samples.

Whiteflies (Bemisia tabaci) are a significant pest of cucurbits and vectors many viruses leading to substantial economic losses. Modern diagnostic tools offer the potential for early detection of viruses in the whiteflies before crop production. One such tool is the multiplex reverse transcriptase quantitative PCR (RT-qPCR) probe-based technique, which can detect multiple targets in a single reaction and simultaneously quantify the levels of each target, with a detection limit of 100 copies per target. In this study, a multiplex RT-qPCR-based detection system capable of identifying one DNA virus and three RNA viruses in whiteflies: cucurbit leaf crumple virus (CuLCrV), cucurbit chlorotic yellows virus (CCYV), cucurbit yellow stunting disorder virus (CYSDV), and squash vein yellowing virus (SqVYV) was developed. To ensure the reliability of the assay, an internal gene control as the fifth target to monitor false-negative results was incorporated. This newly developed molecular diagnostic tool possesses several advantages. It can detect up to five desired targets from a single whitefly RNA sample, even at concentrations as low as 1 ng/µl. To evaluate its sensitivity, we conducted experiments using serially diluted cloned plasmids and in vitro transcribed RNA transcripts of the target viruses. We also assessed the specificity of the assay by including aphid-transmitted viruses and other viruses known to infect cucurbits. The diagnostic method successfully detected all five targets simultaneously and allowed for the quantification of up to 100 copies using a mixture of healthy? RNA and in vitro transcribed RNA. Our aim with this study was to develop a highly specific and sensitive one-step multiplex RT-qPCR system for the simultaneous detection of viruses transmitted by whiteflies in cucurbits. This system offers significant advantages for early detection, enabling prompt control measures to mitigate the further spread of viral infections and reduce yield losses. Additionally, we demonstrated the ability to simultaneously detect mixed viruses (CCYV, CYSDV, CuLCrV, and SqVYV) in individual whiteflies and quantify the number of viral copies carried by each whitefly. The multiplex RT-qPCR assay outperforms currently available techniques for detecting many samples at a given time and can be effectively utilized for early monitoring of plant viruses in individual whiteflies and symptomless plants.

Sanitary Protection of the Territory: Specific Aspects of the Dynamics and Intensity of the Spread of Viral Respiratory Infections in the Rostov Region in 2005–2022

Sanitary Protection of the Territory: Specific Aspects of the Dynamics and Intensity of the Spread of Viral Respiratory Infections in the Rostov Region in 2005–2022

Uncovering and evaluating coconut oil-loaded silica nanoemulsion as anti-viral, bacterial, and fungal: synthesis, fabrication, characterization, and biosafety profiles

BackgroundCoconut oil, a natural component abundant in terpenoids, possesses various physiological functions. The global concern over the spread of viral infections and antimicrobial-resistant bacteria and fungi has highlighted the need for novel treatments. Coconut oil, with its known antimicrobial properties, presents an attractive candidate for combating these pathogens. This study aims to investigate the potential of coconut oil-loaded silica nanoemulsion (ON@SiO2) as a novel therapeutic agent against viral, antimicrobial-resistant bacteria, and fungal pathogens.ResultsThe study synthesized coconut oil-loaded silica nanoemulsion (ON@SiO2) using an eco-friendly, cost-effective method with native coconut oil (CO). Characterization confirmed successful synthesis on the nanoscale with good distribution. Three nanoemulsion samples (ON-1@SiO2, ON-2@SiO2, and ON-3@SiO2) were prepared, with average particle sizes of 193 nm, 200 nm, and 325 nm, respectively. Evaluation of cytotoxicity on Vero-E6 cell lines indicated safety of ON-0@SiO2 and ON-3@SiO2, with CC50 values of 97.5 mg/ml and 89.1 mg/ml, respectively. ON-3@SiO2 demonstrated anti-Herpes I and II (HSV1 and HSV2) activity, with IC50 values of 1.9 mg/ml and 2.1 mg/ml, respectively. Additionally, ON-3@SiO2 exhibited promising antibacterial activity against E. coli, P. aeruginosa, S. aureus, and B. subtilis, with MIC values of 25 mg/ml, 12.5 mg/ml, 25 mg/ml, and 3.12 mg/ml, respectively.ConclusionsON-3@SiO2 showed potential antifungal activity against C. albicans, a unicellular fungus, with an MIC of 12.5 mg/ml. Overall, ON@SiO2 possesses antiviral, antibacterial, and antifungal properties.

Identification of new triazolo annulated dipyridodiazepine derivatives as HIV-1 reverse transcriptase inhibitors: Design, synthesis, DFT, molecular modelling and in silico studies

With the tremendous increase in viral infection spread and drug resistance, it is imperative to explore new efficient antiviral agents. Two series of novel compounds, triazole-annulated dipyridodiazepines 9(a–e) and methyl-substituted triazole-annulated dipyridodiazepines 10(a–e), were successfully synthesised and characterised by IR, NMR spectroscopy and mass spectrometry. The in vitro reverse transcriptase inhibitory ability of synthesized derivatives was determined using an HIV-1 reverse transcriptase assay kit. Results revealed that 9a and 10a were most potent with an IC50 of 66 and 71 nM compared with reference drug nevirapine 88nM. A density functional theory (DFT) study of the synthesized compound showed that both triazole series possess noticeably distorted butterfly-like structures, triazole and pyridine rings tilted relative to the diazepine ring and the phenyl ring is perpendicular to the diazepine ring. Significant HOMO/LUMO gap values for both series, 3.71–4.59 eV for the compounds 9(a–e) and 3.69–4.68 eV for compounds 10(a–e), suggest their quite noticeable stability. Further, these analogues were in silico analysed for molecular docking, drug-likeness, physicochemical and ADMET studies. The good binding scores (high interaction energies) obtained in the molecular docking studies are in good agreement with the molecular electrostatic potential (MEP) analysis results showing accumulations of negative and positive electrostatic potential on different parts of the molecules of the compounds studied. In conclusion, all these results suggest that synthesized analogues could be a potential candidate to inhibit HIV-1 reverse transcriptase and may be considered as lead molecules in the development of new anti-reverse transcriptase agents.

Lumpy Skin Disease: An Emerging Concern in Pakistan and its Impact on National Economic Loss

Lumpy Skin Disease (LSD), an emerging viral infection of cattle and buffalo, poses significant challenges to the livestock industry in Pakistan. Symptoms of this disease include enlarged appearance of lumps, high fever, discharge from the eyes and nose, and loss of appetite. The incubation period of this virus in cattle is approximately 28 days, as per the report of the Food and Agriculture Organization (FAO). This viral infection spreads through direct contact among herds. The World Organization for Animal Health (WOAH) and the FAO both warn that the spread of illnesses could lead to serious economic losses. A considerable financial loss in this industry is due to the mortality rate, reduced milk and meat production rate, and increasing management and treatment expenses. Generally, the best administrative approach to treating this disease is vaccination, which is also an economically effective strategy. This review aims to provide insights into the symptoms, risk factors, control, and disease administrative strategies, economic loss associated with Lumpy Skin Disease, and the potential role of vaccination in future disease management strategies.

A dual fluorescent herpes simplex virus type 1 recombinant reveals divergent outcomes of neuronal infection.

Critical stages of lytic herpes simplex virus type 1 (HSV-1) replication are marked by the sequential expression of immediate early (IE) to early (E), then late (L) viral genes. HSV-1 can also persist in neuronal cells via a non-replicative, transcriptionally repressed infection called latency. The regulation of lytic and latent transcriptional profiles is critical to HSV-1 pathogenesis and persistence. We sought a fluorescence-based approach to observe the outcome of neuronal HSV-1 infection at the single-cell level. To achieve this goal, we constructed and characterized a novel HSV-1 recombinant that enables discrimination between lytic and latent infection. The dual reporter HSV-1 encodes a human cytomegalovirus-immediate early (hCMV-IE) promoter-driven enhanced yellow fluorescent protein (eYFP) to visualize the establishment of infection and an endogenous mCherry-VP26 fusion to report lytic replication. We confirmed that viral gene expression, replication, and spread of infection are not altered by the incorporation of the fluorescent reporters, and fluorescent protein (FP) detection virtuously reports the progression of lytic replication. We demonstrate that the outcome of HSV-1 infection of compartmentalized primary neurons is determined by viral inoculating dose: high-dose axonal inoculation proceeds to lytic replication, whereas low-dose axonal inoculation establishes a latent HSV-1 infection. Interfering with low-dose axonal inoculation via small molecule drugs reports divergent phenotypes of eYFP and mCherry reporter detection, correlating with altered states of viral gene expression. We report that the transcriptional state of neuronal HSV-1 infection is variable in response to changes in the intracellular neuronal environment.IMPORTANCEHerpes simplex virus type 1 (HSV-1) is a prevalent human pathogen that infects approximately 67% of the global human population. HSV-1 invades the peripheral nervous system, where latent HSV-1 infection persists within the host for life. Immunological evasion, viral persistence, and herpetic pathologies are determined by the regulation of HSV-1 gene expression. Studying HSV-1 gene expression during neuronal infection is challenging but essential for the development of antiviral therapeutics and interventions. We used a recombinant HSV-1 to evaluate viral gene expression during infection of primary neurons. Manipulation of cell signaling pathways impacts the establishment and transcriptional state of HSV-1 latency in neurons. The work here provides critical insight into the cellular and viral factors contributing to the establishment of latent HSV-1 infection.

Using SCENTinel® to predict SARS-CoV-2 infection: insights from a community sample during dominance of Delta and Omicron variants.

Based on a large body of previous research suggesting that smell loss was a predictor of COVID-19, we investigated the ability of SCENTinel®, a newly validated rapid olfactory test that assesses odor detection, intensity, and identification, to predict SARS-CoV-2 infection in a community sample. Between April 5, 2021, and July 5, 2022, 1,979 individuals took one SCENTinel® test, completed at least one physician-ordered SARS-CoV-2 PCR test, and endorsed a list of self-reported symptoms. Among the of SCENTinel® subtests, the self-rated odor intensity score, especially when dichotomized using a previously established threshold, was the strongest predictor of SARS-CoV-2 infection. SCENTinel® had high specificity and negative predictive value, indicating that those who passed SCENTinel® likely did not have a SARS-CoV-2 infection. Predictability of the SCENTinel® performance was stronger when the SARS-CoV-2 Delta variant was dominant rather than when the SARS-CoV-2 Omicron variant was dominant. Additionally, SCENTinel® predicted SARS-CoV-2 positivity better than using a self-reported symptom checklist alone. These results indicate that SCENTinel® is a rapid assessment tool that can be used for population-level screening to monitor abrupt changes in olfactory function, and to evaluate spread of viral infections like SARS-CoV-2 that often have smell loss as a symptom.

Nanomedicine for the Treatment of Viral Diseases: Smaller Solution to Bigger Problems.

The continuous evolution of new viruses poses a danger to world health. Rampant outbreaks may advance to pandemic level, often straining financial and medical resources to breaking point. While vaccination remains the gold standard to prevent viral illnesses, these are mostly prophylactic and offer minimal assistance to those who have already developed viral illnesses. Moreover, the timeline to vaccine development and testing can be extensive, leading to a lapse in controlling the spread of viral infection during pandemics. Antiviral therapeutics can provide a temporary fix to tide over the time lag when vaccines are not available during the commencement of a disease outburst. At times, these medications can have negative side effects that outweigh the benefits, and they are not always effective against newly emerging virus strains. Several limitations with conventional antiviral therapies may be addressed by nanotechnology. By using nano delivery vehicles, for instance, the pharmacokinetic profile of antiviral medications can be significantly improved while decreasing systemic toxicity. The virucidal or virus-neutralizing qualities of other special nanomaterials can be exploited. This review focuses on the recent advancements in nanomedicine against RNA viruses, including nano-vaccines and nano-herbal therapeutics.

Does Travel Spread Infection?—Effects of Social Stirring Simulated on SEIRS Circuit Grid

Previous models of the spread of viral infection could not explain the potential risk of non-infectious travelers and exceptional events, such as the reduction in infected cases with an increase in travelers. In this study, we provide an explanation for improving the model by considering two factors. First, we consider the travel of susceptible (S), exposed (E), and recovered (R) individuals who may become infected and infect others in the destination region in the near future, as well as infectious (I). Second, people living in a region and those moving from other regions are treated as separate but interacting groups to consider the potential influence of movement before infection. We show the results of the simulation of infection spread in a country where individuals travel across regions and the government chooses regions to vaccinate with priority. As a result, vaccinating people in regions with larger populations better suppresses the spread of infection, which turns out to be a part of a general law that the same quantity of vaccines can work efficiently by maximizing the conditional entropy Hc of the distribution of vaccines to regions. This strategy outperformed vaccination in regions with a larger effective regeneration number. These results, understandable through the new concept of social stirring, correspond to the fact that travel activities across regional borders may even suppress the spread of vaccination if processed at a sufficiently high pace. This effect can be further reinforced if vaccines are equally distributed to local regions.

Modeling the spread of viral infection in a local atmosphere infected with SARS-COV-2 virus. Constant virion concentration

Представлена математическая модель инфицирования вирусом COVID-19 при абсорбции вирионов из локальной атмосферы. В стандартную эпидемиологическую модель включены новые слагаемые, учитывающие начальный иммунитет и поток микрочастиц патогена из окружающей среды в организм. Показано, что иммунитет уменьшает степень поражения клеток организма и увеличивает интервал времени между началом инфицирования и взрывным ростом концентрации микрочастиц патогена. Начальный иммунитет обеспечивает критическую начальную концентрацию вирионов в организме, превышение которой приводит к интенсивному росту концентрации микрочастиц вируса. При начальной концентрации вирионов меньше критического значения вирус в организме вырождается. Результаты расчетов по модифицированной модели сопоставляются с экспериментальными данными. На начальной стадии инфицирования найдено аналитическое решение, описывающее рост концентрации патогена в организме при постоянном потоке вирионов из атмосферы. Найдено критическое значение потока вирионов из атмосферы, превышение которого приводит к монотонному росту концентрации клеток патогена. Предложена математическая модель вакцинации, снижающей вероятность поражения клеток организма микрочастицами вируса. Проиллюстрированы различные сценарии развития вирусной инфекции в организме индивида, эвакуированного из атмосферы, зараженной вирусом.

Human adenovirus type 3 restores pharmacologically inhibited exosomal cargo in lung carcinoma cells.

Introduction: Drug repurposing is fast growing and becoming an attractive approach for identifying novel targets, such as exosomes for cancer and antiviral therapy. Exosomes are a specialized class of extracellular vesicles that serve as functional mediators in intercellular communication and signaling that are important in normal physiological functions. A continuously growing body of evidence has established a correlation between the abnormal release of exosomes with various viral disease pathologies including cancer. Cells that are virus-infected release exosomes known to influence the process via the loading and transfer of viral components, such as miRNA, small (s) RNA, DNA, and proteins. Inhibition of exosome release may abate the spread and severity of viral infection, thus making exosomes an attractive target for antiviral therapies. We previously demonstrated the pharmacological inhibition of exosomes. Methods: Herein, we used a cell-based assay to determine the effect of Human adenovirus type 3 (HAdV3) on the exosome inhibition process by azole and Heparin derivatives. HAdV3-infected cells were treated with two concentrations of each inhibitor at different time points. Results: HAdV3 activities led to increased total sRNA, DNA, and exosome particle concentrations via particle tracking in the presence of Climbazole and Heparin relative to uninfected exosomes. In addition, there was an increased expression of classical markers such as ALG-2 interacting protein X (ALIX), and tetraspanin (CD63), (p < 0.05) and upregulated transcription factor interferon regulatory factor (IRF) 8 in the presence of HAdV3 after 24hours (h) of treatment. Whereas higher concentrations of Climbazole and Heparin sodium salt were found to inhibit total exosome protein (p < 0.001) and exo-RNA (p < 0.01) content even in the presence of HAdV3 relative to infected exosomes only. Activities of HAdV3 in the presence of selected inhibitors resulted in the positive regulation of exosome related DNA damage/repair signaling proteins. Blocking exosome secretion partially obstructed viral entry. Immunological studies revealed that HAdV3 fiber protein levels in A549 cells were reduced at all concentrations of Climbazole and Heparin and both multiplicities of infections (p < 0.001). Discussion: Our findings suggest that while HAdV may bolster inhibited exosome content and release when modulating certain activities of the endosomal pathway mediators, HAdV entry might be constrained by the activities of these pharmacological agents.