Viral Origin Research Articles

Screening of Efficient Adjuvants for the RBD-Based Subunit Vaccine of SARS-CoV-2.

The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more transmissible, with a reduced sensitivity to vaccines targeting the original virus strain. Therefore, developing an effective vaccine against both the original SARS-CoV-2 strain and its variants is an urgent need. It is known that the receptor-binding domain (RBD) in the S protein of SARS-CoV-2 is an important vaccine target, but subunit vaccines usually have lower immunogenicity and efficacy. Thus, selecting appropriate adjuvants to enhance the immunogenicity of protein-based subunit vaccine antigens is necessary. Here, an RBD-Fc subunit vaccine of SARS-CoV-2 has been generated, followed by vaccination in B6 mice, and four adjuvant regimens were investigated, including aluminum salts (Alum) + 3-O-desacyl-4'-monophosphoryl lipid A (MPL), AddaVax, QS21 + MPL, and Imiquimod. The adjuvant potency was evaluated by comparing the elicited polyclonal antibodies titers with measuring binding to RBD and S protein in ELISA and Western blot analysis, and also the cross-neutralizing antibodies titers using a pseudovirus infection assay of hACE2-expressing 293T cells, with pseudoviruses expressing the S protein of the SARS-CoV-2 original strain and Delta strain. The presence of QS21 + MPL adjuvant induced stronger polyclonal antibody response and neutralization potency blocking the original strain and Delta strain, as compared with the non-adjuvant RBD-Fc group and other adjuvant groups. Meanwhile, Imiquimod even had a negative effect in inducing specific antibodies and cross-neutralizing antibody production as an adjuvant.

The plasticity of biocompatibility

Biocompatibility concerns the phenomena that occur within the interactions between biomaterials and human patients, which ultimately control the performance of many facets of medical technology. It involves aspects of materials science, many different forms of engineering and nanotechnology, chemistry, biophysics, molecular and cellular biology, immunology, pathology and a myriad of clinical applications. It is not surprising that an overarching framework of mechanisms of biocompatibility has been difficult to elucidate and validate. This essay discusses one fundamental reason for this; we have tended to consider biocompatibility pathways as essentially linear sequences of events which follow well-understood processes of materials science and biology. The reality, however, is that the pathways may involve a great deal of plasticity, in which many additional idiosyncratic factors, including those of genetic, epigenetic and viral origin, exert influence, as do complex mechanical, physical and pharmacological variables. Plasticity is an inherent core feature of the performance of synthetic materials; here we follow the more recent biological applications of plasticity concepts into the sphere of biocompatibility pathways. A straightforward linear pathway may result in successful outcomes for many patients; we may describe this in terms of classic biocompatibility pathways. In other situations, which usually command much more attention because of their unsuccessful outcomes, these plasticity-driven processes follow alternative biocompatibility pathways; often, the variability in outcomes with identical technologies is due to biological plasticity rather than material or device deficiency.

Presepsin as a diagnostic and prognostic biomarker of severe bacterial infections and COVID-19

We aimed to develop presepsin as a marker of diagnosis of severe infections of either bacterial and viral origin. The derivation cohort was recruited from 173 hospitalized patients with acute pancreatitis or post-operative fever or infection suspicion aggravated by at least one sign of the quick sequential organ failure assessment (qSOFA). The first validation cohort was recruited from 57 admissions at the emergency department with at least one qSOFA sign and the second validation cohort from 115 patients with COVID-19 pneumonia. Presepsin was measured in plasma by the PATHFAST assay. Concentrations more than 350 pg/ml had sensitivity 80.2% for sepsis diagnosis in the derivation cohort (adjusted odds ratio 4.47; p < 0.0001). In the derivation cohort, sensitivity for 28-day mortality prognosis was 91.5% (adjusted odds ratio 6.82; p: 0.001). Concentrations above 350 pg/ml had sensitivity 93.3% for the diagnosis of sepsis in the first validation cohort; this was 78.3% in the second validation cohort of COVID-19 aiming at the early diagnosis of acute respiratory distress syndrome necessitating mechanical ventilation. The respective sensitivity for 28-day mortality was 85.7% and 92.3%. Presepsin may be a universal biomarker for the diagnosis of severe infections of bacterial origin and prediction of unfavorable outcome.

Prevalence of Intestinal Coccidia: First Description of Cyclosporidiosis Associated with Diarrhea in Children in Colombia

Background: In Colombia, the studies about the etiology of acute diarrhea disease (ADD) in children by using standard stool culture techniques methods and DNA detection tools for intestinal virus show that viral origin was the most frequent, however still between 16 to 45% of the cases of unknown etiology. Specific staining techniques or high sensitivity molecular methods for the intestinal coccidia Cryptosporidium sp and Cyclospora sp have been not applied in the Colombian studies, for this reason, the current situation of these intestinal coccidia in Colombia as cause of diarrhea is unknown. Objective: To estimate the frequency of Cryptosporidium sp. and Cyclospora sp. and to analyze the association between infection and clinical manifestations on children with acute diarrhea consulting the pediatrics emergency service of a third level Hospital. Methods: An observational descriptive study was performed in 150 children that consulted the emergency service at the Hospital San Juan de Dios in Armenia, Colombia, in the period between April 1st and May 31st of 2022. We applied questionnaires and collected primary data from clinical records of children, as well as stool samples of each child after receiving informed consent from the parents and/or legal guardian of the minors. To identify the pathogenic intestinal coccidia (Cryptosporidium sp. and Cyclospora sp.), we used stool fresh preparations with 1% iodine and stained by a modified Ziehl Nielsen coloration protocol (Kinyoun stain). Samples were examined by expert microbiologists on a light microscope with a 40x objective. Prevalence and odds ratios were estimated. For statistical analysis differences in proportions among groups were compared via the X2 test and Fisher exact test. For non-parametric data, differences of means between two groups were analyzed through a Kruskall-Wallis test. Differences of medians were analyzed via Kruskal-Wallis test for non-parametric variables and analysis of variance (ANOVA) for parametric variables; statistical significance was considered when p ≤ 0.05. Statistical calculations were made by using software factors in Epi Info 7.2 Epi-Info version 3.5.1 (CDC, Atlanta). Results: The prevalence of infection in the children that went to the urgency service was of 19,7% by Cryptosporidium sp. and 10,9% by Cyclospora sp. The 59,2% of children with cryptosporidiosis and 66,6% of children with cyclosporidiosis were hospitalized. There was a statistically significant association between the presence of parasite in stools and fever in cyclosporidiosis (93,3% of children with cyclosporidiosis vs. 56% by other causes, OR 10,7 IC95% 1,3-84; p= 0,004). Conclusions: The study results indicate the need to use specific diagnostic techniques to identify Cryptosporidium sp and Cyclospora sp in children with diarrhea, because they are frequent and are treatable with specific antiparasitic medication. We recommend that its search should be done systematically.

Antibiotic prescription patterns for acute upper respiratory tract infections in an outpatient population with health insurance in Syria — a retrospective cross-sectional study

BackgroundAntibacterial resistance is an ongoing global issue, threatening the lives of millions and affecting the quality of health systems, resulting in high costs to the worldwide economy. Syria is one of many countries with a high rate of antibiotic prescription or consumption, even before the war. MethodsA retrospective cross-sectional study was conducted to assess the pattern of antibiotic prescribing with regard to acute upper respiratory tract infection (AURTI) cases throughout the year 2019; data were collected from GlobeMed Syria (now Modern Healthcare Claims Management Company) following ethical approval. ResultsThe study comprised 14 913 cases, of which 13 382 (90%) had received an antibiotic prescription. All age groups showed high prescribing rates, with the 46–55 years age group having the highest (95.0%). Acute tonsillitis had the most significant percentage of antibiotics prescribed (98.7%). Cephalosporins were the most commonly prescribed antibiotic class. Family physicians were more inclined to prescribe antibiotics than those in other specialism groups. ConclusionSyria has a high rate of prescribing antibiotics for AURTIs, which may contribute to the evolution of resistant bacteria. The rate is higher than those reported in other Arab countries. Physicians need to commit to following the official guidelines, taking the appropriate prescribing of antibiotics more seriously, and should take more care in distinguishing viral origins of AURTIs.

Achievements in virus research

This paper brings a brief survey of the achievements in virology as published from the second half of 20th century til now. In beginning, the virus research has been performed at framework of microbiology and/or closely by related biological disciplines, such as parasitology, pathology, mycology and/or cytology. The reason why virologists have been involved in many related scientific disciplines, has been, in addition, because viruses infect not only great many mammalian species, but also lower vertabrates (such as birds and reptiles) and/or certain plants. Even though there could be difficult to assess such great variety of scientific information, a great proportion a great proportion of authors at least has attempted doing with success. Needless to mention that though precise origin of viruses has not been cleared till now, they have probably sequestrated from cellular organelles and then sequently underwent to own (rather independent) evolution

A recent outbreak of human H1N2 infection: correspondence.

A recent outbreak of human H1N2 infection: correspondence.

Les virus dans l’environnement, considérations virologiques et exemples de leur impact en santé humaine

AbstractAnimal viruses are present in most human environments. Their viability in these media is very variable and the most important element that conditions this viability is the existence or not of a phospholipid envelope surrounding the nucleocapsid. After some general considerations on the structure of viruses, their multiplication cycle and their resistance to different physico-chemical agents, some examples of the impact of animal viruses present in the environment on human health will be presented. The situations that are related concern recent epidemiological events: circulation of type 2 polioviruses derived from the Sabin vaccine strain in the wastewater of New York, London and Jerusalem; risk of transmission of Sars-CoV-2 during the spreading of sludge from wastewater treatment plants on agricultural land in the era of the Covid-19 pandemic; « new » forms of food-borne poisoning of viral origin (hepatitis E, tick-borne encephalitis, Nipah virus infection); contamination by epidemic viruses of mobile phones used by pediatricians; role of fomites in the spread of orthopoxvirus infections (smallpox, cowpox, monkeypox). The risk attached to animal viruses present in the environment must be assessed in a measured way without overestimating or underestimating their potential consequences for human health.

Prevalence of neuroinfectious diseases and outcomes in Africa

Prevalence of neuroinfectious diseases and outcomes in Africa

In silico prediction of potential inhibitors for SARS-CoV-2 Omicron variant using molecular docking and dynamics simulation-based drug repurposing

BackgroundIn November 2021, variant B.1.1.529 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified by the World Health Organization (WHO) and designated Omicron. Omicron is characterized by a high number of mutations, thirty-two in total, making it more transmissible than the original virus. More than half of those mutations were found in the receptor-binding domain (RBD) that directly interacts with human angiotensin-converting enzyme 2 (ACE2). This study aimed to discover potent drugs against Omicron, which were previously repurposed for coronavirus disease 2019 (COVID-19). All repurposed anti-COVID-19 drugs were compiled from previous studies and tested against the RBD of SARS-CoV-2 Omicron.MethodsAs a preliminary step, a molecular docking study was performed to investigate the potency of seventy-one compounds from four classes of inhibitors. The molecular characteristics of the best-performing five compounds were predicted by estimating the drug-likeness and drug score. Molecular dynamics simulations (MD) over 100 ns were performed to inspect the relative stability of the best compound within the Omicron receptor-binding site.ResultsThe current findings point out the crucial roles of Q493R, G496S, Q498R, N501Y, and Y505H in the RBD region of SARS-CoV-2 Omicron. Raltegravir, hesperidin, pyronaridine, and difloxacin achieved the highest drug scores compared with the other compounds in the four classes, with values of 81%, 57%, 18%, and 71%, respectively. The calculated results showed that raltegravir and hesperidin had high binding affinities and stabilities to Omicron with ΔGbinding of − 75.7304 ± 0.98324 and − 42.693536 ± 0.979056 kJ/mol, respectively. Further clinical studies should be performed for the two best compounds from this study.Graphical

Photogallery of diseases of the oral mucosa. Part II

Nowadays there are more than 300 types of diseases of the oral mucosa and the red fringe of the lips. The etiology of these lesions is extremely diverse and includes primary and secondary infectious diseases of bacterial, fungal and viral origin, autoimmune diseases, etc. In addition, there are a number of features associated with the age of manifestation of a particular lesion. For example, in childhood, primary rashes with herpes simplex often appear precisely on the oral mucosa. In adults, along with widespread rashes on the skin, it is possible to damage the oral mucosa in Kaposi's sarcoma with predominant localization on the hard palate. In primary and secondary syphilis, rashes on the oral mucosa can often be observed: primary hard chancre, syphilitic tonsillitis, syphilitic papules.&#x0D; This photo gallery presents images with various lesions of the oral mucosa.

The analysis of a cluster of koi herpesvirus disease outbreaks in intensive carp aquaculture using molecular and conventional epidemiology.

The analysis of a cluster of koi herpesvirus disease outbreaks in intensive carp aquaculture using molecular and conventional epidemiology.

Synthesis, Photophysical Characterization and Evaluation of Biological Properties of C7, a Novel Symmetric Tetra-Imidazolium-Bis-Heterocycle

A novel symmetric tetra-imidazolium-bis-heterocycle, called C7, was designed and synthesized in a quick two-step pathway, with the objective to synthesize biologically active supramolecular assembly. The synthesized compound was then analyzed for its photophysical properties, for a potential application in theragnostic (fluorescence) or phototherapy (photodynamic therapy, with the production of reactive oxygen species, such as singlet oxygen 1O2). C7 was thus screened for its biological activity, in particular against important human pathogens of viral origin (respiratory viruses such as adenovirus type 2 and human coronavirus 229E) and of fungal and bacterial origin. The compound showed limited antiviral activity, combined with very good antiproliferative activity against breast cancer, and head and neck squamous cell carcinoma models. Interestingly, the selected compound showed excellent antibacterial activity against a large array of Gram-positive and Gram-negative clinically isolated pathogenic bacteria, with a possible inhibitory mechanism on the bacterial cell wall synthesis studied with electron microscopy and molecular docking tools. Collectively, the newly synthesized compound C7 could be considered as a potential lead for the development of new antibacterial treatment, endowed with basic photophysical properties, opening the door towards the future development of phototherapy approaches.

Human Papillomavirus Genome Copy Number Is Maintained by S-Phase Amplification, Genome Loss to the Cytosol during Mitosis, and Degradation in G1 Phase.

The current model of human papillomavirus (HPV) replication is comprised of three modes of replication. Following infectious delivery, the viral genome is amplified during the establishment phase to reach up to some hundred copies per cell. The HPV genome copy number remains constant during the maintenance stage. The differentiation of infected cells induces HPV genome amplification. Using highly sensitive in situ hybridization (DNAscope) and freshly HPV16-infected as well as established HPV16-positive cell lines, we observed that the viral genome is amplified in each S phase of undifferentiated keratinocytes cultured as monolayers. The nuclear viral genome copy number is reset to pre-S-phase levels during mitosis. The majority of the viral genome fails to tether to host chromosomes and is lost to the cytosol. Cytosolic viral genomes gradually decrease during cell cycle progression. The loss of cytosolic genomes is blocked in the presence of NH4Cl or other drugs that interfere with lysosomal acidification, suggesting the involvement of autophagy in viral genome degradation. These observations were also made with HPV31 cell lines obtained from patient samples. Cytosolic viral genomes were not detected in UMSCC47 cells carrying integrated HPV16 DNA. Analyses of organotypic raft cultures derived from keratinocytes harboring episomal HPV16 revealed the presence of cytosolic viral genomes as well. We conclude that HPV maintains viral genome copy numbers by balancing viral genome amplification during S phase with the loss of viral genomes to the cytosol during mitosis. It seems plausible that restrictions to viral genome tethering to mitotic chromosomes reset genome copy numbers in each cell cycle. IMPORTANCE HPV genome maintenance is currently thought to be achieved by regulating the expression and activity of the viral replication factors E1 and E2. In addition, the E8^E2 repressor has been shown to be important for restricting genome copy numbers by competing with E1 and E2 for binding to the viral origin of replication and by recruiting repressor complexes. Here, we demonstrate that the HPV genome is amplified in each S phase. The nuclear genome copy number is reset during mitosis by a failure of the majority of the genomes to tether to mitotic chromosomes. Rather, HPV genomes accumulate in the cytoplasm of freshly divided cells. Cytosolic viral DNA is degraded in G1 in a lysosome-dependent manner, contributing to the genome copy reset. Our data imply that the mode of replication during establishment and maintenance is the same and further suggest that restrictions to genome tethering significantly contribute to viral genome maintenance.

Determining role of thymus in immune pathogenesis of autoimmune, oncological and infectious diseases

Research data presented in the article are based, mainly, on the concept that thymus, together with bone marrow represent the central organ of immune system being the source of all T cell populations that, following their migration from thymus to periphery, participate in development of immune response to any antigens of viral, bacterial and tissue origin, and to any allergens. This difference is principal, as opposed to the bone marrow which produces other members of immune response, i.e., dendritic cells, macrophages, B cells. E.g., the bone marrow also generates the cells which migrate to thymus where they undergo differentiation to the T cells. Over last 50 years, a plethora of data was accumulated on the leading role of immune system in pathogenesis of virtually all socially significant human diseases affecting the modern mankind, including infectious and malignant disorders, atherosclerosis, autoimmune and allergic diseases. Moreover, current studies show that the aberrant functions of different T cell populations play the leading role in pathogenesis of these diseases. These T cell disturbances in peripheral areas of different organs are proven to develop, mainly in the thymic area. Hence, thymus is a producing organ of T cells with altered functional activities which promote pathogenetic changes in these disorders. Currently, the entire set of immunotherapeutic approaches is aimed for correction of disturbances among the same T cells subpopulations at periphery, without taking into account thymic mechanisms which have induced these disturbances before their emigration from thymus. One should, therefore, develop novel methods and approaches to correct these alterations within thymic area.

Identify the Virus-like Models for COVID-19 as Bio-Threats: Combining Phage Display, Spectral Detection and Algorithms Analysis.

The rapid identification and recognition of COVID-19 have been challenging since its outbreak. Multiple methods were developed to realize fast monitoring early to prevent and control the pandemic. In addition, it is difficult and unrealistic to apply the actual virus to study and research because of the highly infectious and pathogenic SARS-CoV-2. In this study, the virus-like models were designed and produced to replace the original virus as bio-threats. Three-dimensional excitation-emission matrix fluorescence and Raman spectroscopy were employed for differentiation and recognition among the produced bio-threats and other viruses, proteins, and bacteria. Combined with PCA and LDA analysis, the identification of the models for SARS-CoV-2 was achieved, reaching a correction of 88.9% and 96.3% after cross-validation, respectively. This idea might provide a possible pattern for detecting and controlling SARS-CoV-2 from the perspective of combining optics and algorithms, which could be applied in the early-warning system against COVID-19 or other bio-threats in the future.

Insight into Oncogenic Viral Pathways as Drivers of Viral Cancers: Implication for Effective Therapy.

As per a recent study conducted by the WHO, 15.4% of all cancers are caused by infectious agents of various categories, and more than 10% of them are attributed to viruses. The emergence of COVID-19 has once again diverted the scientific community's attention toward viral diseases. Some researchers have postulated that SARS-CoV-2 will add its name to the growing list of oncogenic viruses in the long run. However, owing to the complexities in carcinogenesis of viral origin, researchers across the world are struggling to identify the common thread that runs across different oncogenic viruses. Classical pathways of viral oncogenesis have identified oncogenic mediators in oncogenic viruses, but these mediators have been reported to act on diverse cellular and multiple omics pathways. In addition to viral mediators of carcinogenesis, researchers have identified various host factors responsible for viral carcinogenesis. Henceforth owing to viral and host complexities in viral carcinogenesis, a singular mechanistic pathway remains yet to be established; hence there is an urgent need to integrate concepts from system biology, cancer microenvironment, evolutionary perspective, and thermodynamics to understand the role of viruses as drivers of cancer. In the present manuscript, we provide a holistic view of the pathogenic pathways involved in viral oncogenesis with special emphasis on alteration in the tumor microenvironment, genomic alteration, biological entropy, evolutionary selection, and host determinants involved in the pathogenesis of viral tumor genesis. These concepts can provide important insight into viral cancers, which can have an important implication for developing novel, effective, and personalized therapeutic options for treating viral cancers.

The Politicization of COVID-19 Origin Stories: Insights from a Cross-Sectional Survey in China

The search for the origins of COVID-19 has yielded no conclusive evidence. In the face of this uncertainty, other social and political factors can influence perceptions of virus origins, which in turn can influence policy formation and global efforts to combat future pandemics. Vastly different COVID-19 origin stories may circulate both within the same country but also between different countries. This article examines COVID-19 origins debates as they circulate in China, drawing from a 974-respondent survey conducted in mainland China. Our results show that within China there is a strong belief that COVID-19 originated outside the country, either in the United States or Europe. This contrasts with mainstream media coverage in the United State and Europe, which generally holds that the virus most likely originated in China. Given such global dissonance, moving forward with pandemic prevention reforms is challenging. Yet, even in the face of such diverse beliefs, building support for reform is still possible. As the search for COVID-19 continues, policy reform can be pursued across a plurality of domains, including wet markets, the wildlife trade, cold-chain products, and gain-of-function virology research, all in the interest of preventing the next global pandemic.

PREHOST: Host prediction of coronaviridae family using machine learning

Coronavirus, a zoonotic virus capable of transmitting infections from animals to humans, emerged as a pandemic recently. In such circumstances, it is essential to understand the virus's origin. In this study, we present a novel machine-learning pipeline PreHost for host prediction of the family, Coronaviridae. We leverage the complete viral genome and sequences at the protein level (spike protein, membrane protein, and nucleocapsid protein). Compared with the current state-of-the-art approaches, the random forest model attained high accuracy and recall scores of 99.91% and 0.98, respectively, for genome sequences. In addition to the spike protein sequences, our study shows membrane and nucleocapsid protein sequences can be utilized to predict the host of viruses. We also identified important sites in the viral sequences that help distinguish between different host classes. The host prediction pipeline PreHost will cater as a valuable tool to take effective measures to govern the transmission of future viruses.

On the 130th Anniversary of Virology – Historical Aspects of the Study of Viruses which Cause Infectious Diseases in Farm Animals

The year 2022 witnessed the 130th anniversary of the virology science. It was the Russian scientist Dmitri Ivanovsky who proved in 1892, for the first time, the existence of a virus (a new type of pathogen). On February 14, 1892 the results of his research were presented in the report "On two tobacco diseases" at the Academy of Sciences, and later on published in the journal "Agriculture and Forestry". For many decades, every year saw rising interest in viruses, these microscopic extracellular life forms which stand between the living and the non-living, and are capable of infecting cells of living organisms, including bacteria. To this day, the origin of viruses remains one of the most interesting mysteries of biology. There are thousands of viruses which have been studied, however, there are still millions of unknown microorganisms. Viruses in the past and at present remain one of the main etiologic agents of many infectious diseases and they are of great practical interest for veterinary medicine, healthcare and crop production. The virology science have set in long before the viruses themselves were discovered. Back at the end of the XVIII century, a British physician Edward Jenner made the greatest discovery - he developed a live vaccine against smallpox, with which the world began the fight against this terrible disease. After that Louis Pasteur created a method of vaccinations using live weakened vaccines against other diseases, thereby laying the foundation for the scientific justification of the fight against viral diseases.