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Introduction: The curve of spee plays an important role to create Christensen’s phenomenon in natural dentition. This study was performed to assess the difference in depth of the curve of Spee between normal and attrited dentition. Methods: An analytical cross-sectional study was performed to measure the depth of curve speed in a total of 80 willing participants who met the inclusion criteria, of which 40 had normal dentition and 40 had attrited dentition. Measurements were done on stone casts by using a rigid metal scale and a digital vernier caliper. Analytical statistical analysis (independent t-test) was done using SPSS Statistical Software Package (version 21.0). Results: There was a statistically significant difference in the depth of the curve of Spee between the two groups. Conclusions: The depth of the curve of spee decreases with the advancing of the age of human as attrition of the teeth occurs with age. Although there is a decrease in the depth of the curve of spee it should be maintained and created while performing full mouth rehabilitation and other extensive prosthodontic treatments.

The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has been proven to be more severe than the previous coronavirus outbreaks due to the virus’ high transmissibility. With the emergence of new variants, this global phenomenon took a more dramatic turn, with many countries recently experiencing higher surges of confirmed cases and deaths. On top of this, the inadequacy of effective treatment options for COVID-19 aggravated the problem. As a way to address the unavailability of target-specific viral therapeutics, computational strategies have been employed to hasten and systematize the search. The objective of this review is to provide initial data highlighting the utility of polyphenols as potential prophylaxis or treatment for COVID-19. In particular, presented here are virtually screened polyphenolic compounds which showed potential as either antagonists to viral entry and host cell recognition through binding with various receptor-binding regions of SARS-CoV-2 spike protein or as inhibitors of viral replication and post-translational modifications through binding with essential SARS-CoV-2 non-structural proteins.

Hepatitis C is a liver illness caused by the hepatitis C virus (HCV). Acute and chronic hepatitis can be caused by the virus. Hepatitis C infection affects an estimated 71 million people worldwide. Two hundred blood samples were collected (128 males and 72 females), ranged in age from 4 to 80 years and diagnosed through a rapid test and the real time-PCR from the teaching medical city hospital in Baghdad from October 2018 until April 2019. The results showed that 89 samples were positive for HCV by serological tests, and other samples are not. Also, the most frequent age of infection of HCV was between 51 and 80 years. In all samples, the partial region of the NS5A gene was successfully amplified and sequenced. PCR-sequencing revealed three subtyping were; subtype 1a, 1b, and 4a. Phylogenetic analysis revealed subtype concordance of 99 % with a bootstrap hepatitis C virus subtype 1b isolate AASN1 Iraq (ID:MT554101.1). The clusters including HCV subtype 1a isolate AASN20 Iraq (ID:MT554100.1) the identical 96 %, and the clusters including HCV subtype 4a isolate AASN35 Iraq (ID:MT554099.1) the identical 99%.

Chronic inflammation caused by persistent infections and metabolic disorders is thought to contribute to the increased cancer risk and the accelerated cancer progression. Oppositely, acute inflammation induced by bacteria-based vaccines or that is occurring after cancer selectively inhibits cancer progression and metastasis. However, the interaction between inflammation and cancer may be more complex than the current explanations for the relationship between chronic and acute inflammation and cancer. In this review, we described the impact of inflammation on cancer on the basis of three perspectives, including inflammation with different durations (chronic and acute inflammation), different scopes (systemic and local inflammation) and different occurrence sequences (inflammation occurring after and before cancer). In addition, we also introduced bacteria/virus-based cancer immunotherapies. We perceive that inflammation may be a double-edged sword with cancer-promoting and cancer-suppressing functions in certain cases. We expect to further improve the understanding of the relationship between inflammation and cancer and provide a theoretical basis for further research on their complex interaction.

Coronavirus disease 2019 has affected more than 4 million people throughout the world since December 2019. It seems this infection has been the most insidious virus of the coronavirus family. This virus causes severe respiratory failure and symptoms in patients and can result in death. Designing a restrict protocol to deal with infections from severe acute respiratory syndrome coronavirus type 2 is critical in cell therapy institutes. In this review, we present the important aspects related to this virus in cell therapy protocols.

Background Enhanced nonpharmaceutical interventions (NPIs) to prevent the Coronavirus Disease 2019 (COVID-19) have shown various levels of impact on common respiratory pathogens. We aimed to analyze the epidemiological changes seen in certain common respiratory viruses found in Taiwanese children (e.g., influenza virus, enterovirus, parainfluenza virus, adenovirus and respiratory syncytial virus (RSV)) after the implementation of public health measures, as well as interpret the possible meaning of these changes. Methods This retrospective observational study examined the viral isolation from children younger than 18 years at a medical center in central Taiwan during the period January 2015 – December 2020, a time frame of six years. Viral isolations prior to the COVID-19 pandemic (January 2015 – December 2019), along with those during the post-COVID-19 period (January – December 2020) were analyzed and compared. Results A total of 6,899 throat swab samples were collected during the pre-pandemic period of 2015 to 2019, with 2,681 of them having a positive result (38.86%). There were a total of 713 samples collected in 2020, with 142 of them showing positive results (19.92%). The overall positive rate of viral isolates significantly decreased in 2020 (p < 0.001). Declines in the isolation of the influenza virus, parainfluenza virus, adenovirus and enterovirus were observed. The RSV surprisingly became the leading isolate, with up to 47 (6.59%) instances in 2020, and showing an unusual peak in the winter of 2020. The rise began in September of 2020 and reached its plateau in November of that year. Conclusions Most respiratory viruses decreased under NPIs regarding SARS-CoV-2. However, the RSV outbreak in the winter of 2020 had shown the limitation of current NPIs. Possible explanations have been discussed in details and public preventive measures should be reinforced for RSV, particularly amongst people having young children both at home and in care centers.

In early 2013, human infections caused by a novel H7N9 avian influenza virus (AIV) were first reported in China; these infections caused severe disease and death. The virus was initially low pathogenic to poultry, enabling it to spread widely in different provinces, especially in live poultry markets. Importantly, the H7N9 low pathogenic AIVs (LPAIVs) evolved into highly pathogenic AIVs (HPAIVs) in the beginning of 2017, causing a greater threat to human health and devastating losses to the poultry industry. Fortunately, nationwide vaccination of chickens with an H5/H7 bivalent inactivated avian influenza vaccine since September 2017 has successfully controlled H7N9 avian influenza infections in poultry and, importantly, has also prevented human infections. In this review, we summarize the biological properties of the H7N9 viruses, specifically their genetic evolution, adaptation, pathogenesis, receptor binding, transmission, drug resistance, and antigenic variation, as well as the prevention and control measures. The information obtained from investigating and managing the H7N9 viruses could improve our ability to understand other novel AIVs and formulate effective measures to control their threat to humans and animals.

Background: The novel coronavirus 2019 (COVID-19) infection has caused the global emergence of coronavirus in humans during the last 12 months. Till May 11, 2021, the confirmed global COVID-19 cases and deaths reached 158551526 and 3296855, respectively. Methods: Goblet cells and ciliated cells in the nose act as the initial infection site of SARS-CoV-2. Thus, mucus immunity is important to protect from infection. The outburst of SARS-CoV-2 infection can be halted only when an effective vaccine will be developed. Results: Globally, over 100 different vaccines are under investigation, including DNA vaccines, RNA vaccines, inactivated virus vaccines, adenovirus-based vaccines, recombinant/subunit protein vaccines, peptide vaccines, virus-like particles, etc. Inactivated virus vaccines and mRNA, and adenovirus-based vaccines have moved fast into clinical trials. Conclusion: Vaccines containing spike protein of SARS-CoV as subunit could effectively prevent binding of coronavirus to the host cell and membrane fusion. Thus, spike protein can be used as a major target for subunit vaccine preparation.

Many microorganisms have mechanisms that protect cells against attack from viruses. The fermentation components of Streptomyces sp. 1647 exhibit potent anti-influenza A virus (IAV) activity. This strain was isolated from soil in southern China in the 1970s, but the chemical nature of its antiviral substance(s) has remained unknown until now. We used an integrated multi-omics strategy to identify the antiviral agents from this streptomycete. The antibiotics and Secondary Metabolite Analysis Shell (antiSMASH) analysis of its genome sequence revealed 38 biosynthetic gene clusters (BGCs) for secondary metabolites, and the target BGCs possibly responsible for the production of antiviral components were narrowed down to three BGCs by bioactivity-guided comparative transcriptomics analysis. Through bioinformatics analysis and genetic manipulation of the regulators and a biosynthetic gene, cluster 36 was identified as the BGC responsible for the biosynthesis of the antiviral compounds. Bioactivity-based molecular networking analysis of mass spectrometric data from different recombinant strains illustrated that the antiviral compounds were a class of structural analogues. Finally, 18 pseudo-tetrapeptides with an internal ureido linkage, omicsynins A1–A6, B1–B6, and C1–C6, were identified and/or isolated from fermentation broth. Among them, 11 compounds (omicsynins A1, A2, A6, B1–B3, B5, B6, C1, C2, and C6) are new compounds. Omicsynins B1–B4 exhibited potent antiviral activity against IAV with the 50% inhibitory concentration (IC50) of approximately 1 µmol∙L–1 and a selectivity index (SI) ranging from 100 to 300. Omicsynins B1–B4 also showed significant antiviral activity against human coronavirus HCoV-229E. By integrating multi-omics data, we discovered a number of novel antiviral pseudo-tetrapeptides produced by Streptomyces sp. 1647, indicating that the secondary metabolites of microorganisms are a valuable source of novel antivirals.

Epstein–Barr virus (EBV)-infected plasma cell mucositis (PCM) presenting as concurrent oral and laryngeal lesions. A 77-year-old woman presented with gingival swelling, soreness, a dry cough, and hoarseness. Incisional biopsies of the gingiva and larynx were performed. Histological examination revealed PCM. Dramatic improvement was observed after systemic glucocorticoid administration. The serum free light chain levels were correlated with disease activity. EBV infection boosts local B cell lymphoproliferation. Various immunosuppressive states trigger direct EBV-mediated activation of B cell lymphoproliferation by suppressing the functions of T cells. This case suggests a possible pathogenetic mechanism of plasma cell lymphoproliferation of the PCM.

The factors leading to the global emergence of enterovirus D68 (EV-D68) in 2014 as a cause of acute flaccid myelitis (AFM) in children are unknown. To investigate potential changes in virus transmissibility or population susceptibility, we measured the seroprevalence of EV-D68-specific neutralising antibodies in serum samples collected in England in 2006, 2011 and 2017. Using catalytic mathematical models, we estimate an approximately two-fold increase in the basic reproduction number over the 10-year study period, coinciding with the emergence of clade B around 2009. Despite such increase in transmission, the virus was already widely circulating before the AFM outbreaks and the increase of infections by age cannot explain the observed number of AFM cases. Therefore, the acquisition of or an increase in neuropathogenicity would be additionally required to explain the emergence of outbreaks of AFM. Our results provide evidence that changes in enterovirus phenotypes cause major changes in disease epidemiology.

BACKGROUND MXPyV, like MWPyV, was identified in stool samples from children suffering diarrhea in Mexico. In this study, we used a home-made real time PCR to investigate the presence of this novel viruses in stool specimen collected from under-Five- Year-Old Children with gastroenteritis. METHODS A total of 192 fecal specimens previously screened for RV, ADV, NoV, HPeV and SaV, were tested for MWPyV with Taqman real time PCR. RESULTS The most commonly detected virus was NoV GII (33.8%), followed by RV (21.3%), SaV (10.9%), HPeV(8%), NoV GI (6.7%) and AdV (1%). Real time PCR detected MWPyV in 1/192 (0.5%) patients. CONCLUSIONS We detected MWPyV in 0.5% of fecal specimens collected from pediatric patients suffering gastroenteritis which is smaller than the previously reported in literature (4.4% in Australia and 12% Mexico).

Pre existing immunity to Adeno-Associated Virus (AAV) poses a concern in AAV vector– mediated gene therapy. Localized administration of low doses of carefully chosen AAV serotypes can mitigate the risk of an immune response. This article will illustrate the low risk of immune response to AAV serotype 2 vector–mediated gene therapy to the brain with support from clinical trial data in aromatic L-amino acid decarboxylase deficiency and Parkinson disease.

Sensitive PCR detection of viral nucleic acids plays a critical role in infectious disease research, diagnosis and monitoring. In the context of SARS-CoV-2 detection, recent reports indicate that digital PCR-based tests are significantly more sensitive than traditional qPCR tests. Numerous factors can influence digital PCR reaction sensitivity. In this review, using a model for human HIV infection and the Raindance ddPCR platform as an example, we describe technical aspects that contribute to sensitive viral signal detection in DNA and RNA from tissue samples, which often harbor viral reservoirs and serve as better predictors of disease outcome and indicators of treatment efficacy.

In this study, SB216763 and cyclosporine A were identified as anti-influenza A virus (IAV) agents by transcriptome signature reversion (TSR) analysis through deep mining of the cellular transcriptome of human airway and lung cell lines infected with 3 strains of IAV and the chemical perturbations library. A synergistic effect of SB216763 and cyclosporine A against influenza A was disclosed by quantification of the network-based relationship, which was validated in vitro. Along with burgeoning omics approaches, transcriptome-based drug development is flourishing, which provides a novel insight into antivirals discovery with comprehensive cellular transcriptional information of disease and chemical perturbations in multicomponent intervention. This strategy can be applied as a new approach in discovering multitarget antiviral agents from approved drugs, clinical compounds, natural products or other known bioactive compounds.

By December 2019, humanity was challenged by a new infectious respiratory disease named coronavirus disease of 2019 or COVID-19. This is a viral infection based on the presence of the previously non-problematic coronavirus with assigned number 2. This virus causes severe acute respiratory distress and is known now as SARS-CoV2. Since SARS-CoV2 is an RNA virus, remdesivir and favipiravir, both broad-spectrum RNA polymerase inhibitors, were repurposed for treating COVID-19 patients. Remdesivir and favipiravir are antimetabolites, and they are structurally related to the naturally occurring structural elements of RNA. Both agents are prodrugs and must be activated intracellularly to exert their effects through numerous and different mechanisms of action. Efforts have been exerted to determine their efficacy and safety against COVID-19 through clinical trials. Clinical trials have shown an association of remdesivir with increased frequency of adverse effects (in comparison to favipiravir). Nevertheless, the data obtained with remdesivir resulted in its approval by the FDA on the 22nd of October 2020 for COVID-19 treatment. At present, remdesivir is being recommended by several treatment guidelines for the treatment of COVID-19 patients. The evidence in favor of favipiravir is compromised by the small number and low-quality of trials conducted. Favipiravir has shown various benefits when administered in mild and moderate cases of COVID-19, while remdesivir was more beneficial in more severe cases of the disease. Since the two agents are suitable for different groups of patients, both drugs can play a significant role in fighting this pandemic. The goal of this work is to summarize the information available on two antimetabolites - remdesivir and favipiravir - and to compare clinical experience obtained so far with these two agents in COVID-19 patients.

To determine if biological sex and age intersect to affect universal influenza vaccine-induced immunity, adult and aged male and female C57BL/6 mice were sequentially immunized with a chimeric-hemagglutinin (cHA) stalk-based H1 vaccine. Adult mice developed greater quantity and quality of H1-stalk antibodies, that were more cross-reactive with other group 1, but not group 2, influenza viruses, than aged mice. The vaccine did not induce neutralizing or hemagglutination inhibition antibodies, but rather antibody-dependent cellular cytotoxicity, which was greater in adult than aged mice. Vaccinated adult mice were better protected than aged mice after challenge with 2009 H1N1 virus, experiencing less morbidity and having lower pulmonary virus titers. The age-associated decline in immunity and protection was consistently greater among females than males, with the reduction in immunity and protection for aged as compared with adult females often being the sole comparison driving the overall age-associated significant differences. The age-associated reduction in stalk-based immunity in females was not, however, associated with changes in estradiol. To determine if the better antibodies in adults could be utilized to protect aged mice, serum was passively transferred from vaccinated adult mice into naïve sex-matched aged mice. Even with transferred serum from young adult mice, aged females still suffered greater morbidity than aged males. These data suggest there are sex-dependent effects of aging on cHA-based universal influenza virus vaccine-induced immunity that cannot be reversed through transfer of serum from young animals. The lack of consideration of sex-specific effects of aging on immunity could hinder efforts toward universal vaccines.

The ability of HIV-1 to evade neutralizing antibodies (NAbs) in vivo is well demonstrated, but the impact of NAb escape mutations on HIV-1 phenotype other than immune escape itself has rarely been studied. Here, we show that immune escape mutations selected by V3-glycan specific NAbs in vivo can alter the coreceptor usage repertoire of the transmitted/founder (T/F) HIV-1. In a participant developed V3-glycan NAb response, naturally selected mutations at the V3 N301 and N332 glycan sites abrogated CCR8 usage while conferred APJ usage on the cognate T/F strain. Mutations at the N301 glycan also impaired CCR3 usage and partially compromised the efficiency in using CCR5, which could be fully restored by a single escape mutation at the N332 glycan site. Our study demonstrates the link between NAb escape and coreceptor usage alteration in natural HIV-1 infection and indicates that NAb response could drive virus entry tropism evolution in vivo.

Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, desirability of different routes of administration, and emergence of SARS-CoV-2 variants such as the Delta variant. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden Syrian hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titers of blood anti-RBD IgG as well as detectable mucosal responses. Neutralizing antibody activity against wild-type and Delta variants was evident in all vaccinated subjects. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided body mass loss, had lower virus titers in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches.

Hepatitis B virus is a small enveloped RNA virus, which replicates independently but requires the hepatitis B virus (HBV) to provide the envelope proteins necessary for the assembly of its own viral particles. Approximately 5% of chronic hepatitis B virus carriers are infected with HDV. HBV vaccination remains the best preventive treatment for HDV. All HBV patients should be screened for HDV (anti-HDV serology). In case of positive HDV serology, HDV replication (HDV RNA) should be investigated using a sensitive and specific technique. Hepatitis Delta is often complicated by cirrhosis and hepatocellular carcinoma (HCC). For this reason, every patient with Delta cirrhosis should be screened for HCC by abdominal ultrasound every 6 months. The historical treatment was based on PEG-IFN with many side effects. A new treatment has been approved, Bulevirtide (Hepcludex®) an HDV/HBV entry inhibitor, for any patient with chronic hepatitis Delta infection (CHD) with active replication (except in decompensated cirrhosis), at a dose of 2mg/day by subcutaneous injection. The exact duration on-treatment is unknown, thus treatment should be continued if clinical benefit is observed.

Hemolytic anemia and pure red cell aplasia are rare hematological complications of hepatitis B virus infection. We herein report a 24-year-old man who was diagnosed with hemolytic anemia and possible transient pure red cell anemia eight weeks after a severe episode of acute hepatitis B virus infection. Rapid recovery was observed with conservative management. Hemoglobin returned to baseline within three months. As the clinical features of hemolytic anemia associated with hepatitis B virus have not yet been elucidated, we conducted a systematic review and present an analysis of the 20 reported cases, including our present case.

Patients with established rheumatoid arthritis (RA) demonstrate altered immune responses to Epstein-Barr virus (EBV), but the presence and roles of EBV have not been fully explored during the pre-clinical disease period. This study was undertaken to determine if EBV infection, as evidenced by an altered anti-EBV antibody response, either plays an important role in driving the development of RA or is a result of expanded RA-related autoimmunity.A total of 83 subjects with RA according to the 1987 American College of Rheumatology (ACR) criteria and 83 age-, sex-, and race-matched control subjects without RA were included in our study. We collected sera from RA subjects and matched controls during the pre-RA and post-RA diagnosis periods and tested the sera for the presence of 5 anti-EBV antibodies (anti-EBV nuclear antigen 1 IgG isotype, anti-viral capsid antigen [anti-VCA] isotypes IgG and IgA, and anti-early antigen [EA] isotypes IgG and IgA), 7 RA-related autoantibodies (rheumatoid factor measured by nephelometry [RF-Neph] as well as isotype-specific IgA-RF, IgM-RF, and IgG-RF, and anti-cyclic citrullinated peptide [anti-CCP] antibodies, including anti-CCP2, anti-CCP3, and anti-CCP3.1), 22 cytokines/chemokines, 36 individual anti-citrullinated protein antibodies, and IgG-cytomegalovirus (CMV) antibodies. Random forest classification, mixed modeling, and joint mixed modeling were used to determine differences in anti-EBV antibody levels between RA subjects and controls.Random forest analysis identified the presence of preclinical EBV antibodies in the serum that differentiated RA subjects from controls without RA. Specifically, IgG-EA antibody levels were higher in RA subjects (mean ± SD 0.82 ± 0.72 international standardized ratio [ISR]) compared to controls (mean ± SD 0.49 ± 0.28 ISR). In subjects with RA, elevated serum IgG-EA levels in the preclinical period before seroconversion were significantly correlated with increased serum IgM-RF levels (P = 0.007), whereas this correlation was not seen in control subjects without RA (P = 0.15). IgG-CMV antibody levels did not differ between groups.Subjects whose serum IgG-EA antibody levels are elevated in the preclinical period will eventually develop RA, which suggests that EBV reactivation cycles are increased during the preclinical period of RA. A combination of RF and EBV reactivation may play an important role in the development of RA.

Quantifying the composition of viral vectors used in vaccine development and gene therapy is critical for assessing their functionality. Adeno-Associated Virus (AAV) vectors, which are the most widely used viral vectors for in-vivo gene therapy, are typically characterized using PCR, ELISA, and Analytical Ultracentrifugation which require laborious protocols or hours of turnaround time. Emerging methods such as Charge-Detection Mass Spectroscopy, Static Light Scattering, and Mass Photometry offer turnaround times of minutes for measuring AAV mass, but mostly require purified AAV-based reference materials for calibration. Here, we demonstrate a method for using Suspended Nanomechanical Resonators (SNR) to directly measure both AAV mass and aggregation from a few microliters of sample within minutes. We achieve a resolution near 10 zeptograms which corresponds to 1% of the genome holding capacity of the AAV capsid. Our results show the potential of our method for providing real-time quality control of viral vectors during biomanufacturing.

During the current SARS-CoV-2 pandemic, a variety of mutations have accumulated in the viral genome, and currently, four variants of concern (VOCs) are considered potentially hazardous to human society1. The recently emerged B.1.617.2/Delta VOC is closely associated with the COVID-19 surge that occurred in India in the spring of 20212. However, its virological properties remain unclear. Here, we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates spike protein cleavage and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity than its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity., SARS-CoV-2デルタ株に特徴的なP681R変異は ウイルスの病原性を増大させる. 京都大学プレスリリース. 2021-11-26.

Brilacidin, a mimetic of host defense peptides (HDPs), is currently in Phase 2 clinical trial as an antibiotic drug candidate. A recent study reported that brilacidin has antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by inactivating the virus. In this study, we discovered an additional mechanism of action of brilacidin by targeting heparan sulfate proteoglycans (HSPGs) on the host cell surface. Brilacidin, but not acetyl brilacidin, inhibits the entry of SARS-CoV-2 pseudovirus into multiple cell lines, and heparin, an HSPG mimetic, abolishes the inhibitory activity of brilacidin on SARS-CoV-2 pseudovirus cell entry. In addition, we found that brilacidin has broad-spectrum antiviral activity against multiple human coronaviruses (HCoVs) including HCoV-229E, HCoV-OC43, and HCoV-NL63. Mechanistic studies revealed that brilacidin has a dual antiviral mechanism of action including virucidal activity and binding to coronavirus attachment factor HSPGs on the host cell surface. Brilacidin partially loses its antiviral activity when heparin was included in the cell cultures, supporting the host-targeting mechanism. Drug combination therapy showed that brilacidin has a strong synergistic effect with remdesivir against HCoV-OC43 in cell culture. Taken together, this study provides appealing findings for the translational potential of brilacidin as a broad-spectrum antiviral for coronaviruses including SARS-CoV-2.

The most severe consequences of dengue virus infection include shock, haemorrhage, and major organ failure; however, the frequency of these manifestations varies, and the relative contribution of pre-existing anti-dengue virus antibodies, virus characteristics, and host factors (including age and comorbidities) are not well understood. Reliable characterisation of the epidemiology of severe dengue first depends on the use of consistent definitions of disease severity. As vaccine trials have shown, severe dengue is a crucial interventional endpoint, yet the infrequency of its occurrence necessitates the inclusion of thousands of study participants to appropriately compare its frequency among participants who have and have not been vaccinated. Hospital admission is frequently used as a proxy for severe dengue; however, lack of specificity and variability in clinical practices limit the reliability of this approach. Although previous infection with a dengue virus is the best characterised risk factor for developing severe dengue, the influence of the timing between dengue virus infections and the sequence of dengue virus infections on disease severity is only beginning to be elucidated. To improve our understanding of the diverse factors that shape the clinical spectrum of disease resulting from dengue virus infection, prospective, community-based and clinic-based immunological, virological, genetic, and clinical studies across a range of ages and geographical regions are needed.

Objective: To determine if non‐pharmaceutical interventions (NPIs) impacted on respiratory virus detections in Queensland, Australia, during the COVID‐19 pandemic year of 2020. Methods: We analysed weekly counts of influenza, human metapneumovirus, parainfluenza, respiratory syncytial virus, rhinovirus, and adenovirus available from a Queensland laboratory network for the year 2020. These were compared with averaged counts from 2015 to 2019. Results: Overall, 686,199 tests were performed. The timing of NPI implementation was associated with a sharp and sustained decline in influenza, where during the typical annual influenza season (weeks 23–40) no cases were detected from 163,296 tests compared with an average of 26.1% (11,844/45,396) of tests positive in 2015–2019. Similar results were observed for human metapneumovirus and parainfluenza. Respiratory syncytial virus detections also declined but increased in weeks 48–52 (5.6%; 562/10,078) to exceed the 2015–2019 average (2.9%; 150/5,018). Rhinovirus detections increased after schools reopened, peaking in weeks 23–27 (57.4%; 36,228/63,115), exceeding the 2017–2019 detections during that period (21.9%; 8,365/38,072). Conclusions: NPIs implemented to control COVID‐19 were associated with altered frequency and proportions of respiratory virus detections. Implications for public health: NPIs derived from influenza pandemic plans were associated with profound decreases in influenza detections during 2020.

Abstract: Due to its fast international spread and substantial mortality, the coronavirus disease COVID-19 evolved to a global threat. Since there is currently no causative drug against this viral infection available, science is striving for new drugs and other approaches to treat the new disease. Studies have shown that the cell entry of coronaviruses into host cells takes place through the binding of the viral spike (S) protein to cell receptors. Priming of the S protein occurs via hydrolysis by different host proteases. The inhibition of these proteases could impair the processing of the S protein, thereby affecting the interaction with the host-cell receptors and preventing virus cell entry. Hence, inhibition of these proteases could be a promising strategy for treatment against SARSCoV- 2. In this review, we discuss the current state of the art of developing inhibitors against the entry proteases furin, the transmembrane serine protease type-II (TMPRSS2), trypsin, and cathepsin L.

Abstract: The world population has suffered as a result of the COVID-19 pandemic. The disease has become life-threatening in a very short time, harming citizens and the economic systems globally. The novel virus SARS-CoV-2 has been known as the causative agent of COVID-19. The SARS-CoV-2 is a single-stranded RNA virus having ~30 kb genomic components, which are 70% identical to SARS-CoV. The main process of the pathophysiology of COVID-19 has been associated with the interaction of a novel coronavirus with host cell receptor, angiotensin-converting enzyme-2 (ACE 2), by fusion. Therapeutic agents having serine protease inhibitors and ACE-2 blockers may be explored for the treatment by inhibiting the viral target such as Mpro, RdRp, PLpro, and helicase. Herbal medicine has a wide array of chemical entities with potential health benefits, including antiviral activity, which may be explored as an alternative treatment for COVID-19. The herbal bioactives like catechins, andrographolide, hesperidin, biorobin, scutellarein, silvestrol, shikonin, tryptanthrin, vitexin quercetin, myricetin, caffeic acid, psoralidin, luteolin, etc. have shown potential inhibitory effect against SARS-CoV-2. Recent research reports indicate that the various plant secondary metabolites have shown potential antiviral activities. The present review article highlights the recent information on the mechanism of actions and applications of herbal medicine in the treatment of COVID-19.

Background: The Covid-19 virus emerged a few months ago in China and infections rapidly escalated into a pandemic. Objective: To date, there is no selective antiviral agent for the management of pathologies associated with covid-19 and the need for an effective agent against it is essential. Method: In this work two home-made databases from synthetic quinolines and coumarins were virtually docked against viral proteases (3CL and PL), human cell surface proteases (TMPRSS2 and furin) and spike proteins (S1 and S2). Chloroquine, a reference drug without a clear mechanism against coronavirus was also docked on mentioned targets and the binding affinities compared with title compounds. Result: The best compounds of synthetic coumarins and quinolines for each target were determined. All compounds against all targets showed binding affinity between -5.80 to -8.99 kcal/mol in comparison with the FDA-approved drug, Chloroquine, with binding affinity of -5.7 to -7.98 kcal/mol. Two compounds, quinoline-1 and coumarin-24, were found to be effective on three targets – S2, TMPRSS2 and furin – simultaneously, with good predicted affinity between -7.54 to -8.85 kcal/mol. In silico ADME studies also confirmed good oral absorption for them. Furthermore, PASS prediction was calculated and coumarin-24 had higher probable activity (Pa) than probable inactivity (Pi) with acceptable protease inhibitory as well as good antiviral activity against Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) and influenza. Conclusion: Quinoline-1 and Coumarin-24 have the potential to be used against Covid-19. Hence these agents could be useful in combating covid-19 infection after further in vitro and in vivo studies.

Introduction The assessment of the risk of virus transmission through papers, such as postcards, is important. However, the stability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) on different types of papers is currently unknown. Investigation of the survival time of these viruses on different types of papers will provide insights into their risk of long-distance transport by postal items. Methods We evaluated the stability of SARS-CoV-2 and IAV, mixed with a culture medium, on the surface of postcards with various coatings, including plain paper (PP), inkjet paper (IP), and inkjet photo paper (IPP). The surface structure of each paper was microscopically assessed. Results The surface structures of PP, IP, and IPP varied greatly depending on the presence or absence, and type, of coat layer, regardless of the base material. IP and IPP surfaces were less conducive to virus survival than PP surfaces, because of the difference in surface shapes. The survival times of SARS-CoV-2 on each paper were approximately 59.8 (PP), 6.5 (IP), and 9.8 h (IPP), and significantly longer than those of IAV (10.3, 1.8, and 3.3 h, respectively). Conclusions The risk of SARS-CoV-2 transmission via paper, such as postcards, is significantly higher than that of IAV transmission. While PP, IP, and IPP have the same base material, their surface structures differ, which affects viral stability. The IP and IPP surfaces are less suitable for virus survival. This study provides novel insights into the risks of viral transmission via paper.

Objective: Persistence of the viral reservoir is the main barrier to curing HIV. Initiation of ART during acute HIV infection can limit the size and diversity of the reservoir. In depth characterization of the reservoir in individuals who initiate ART during acute infection will be critical for clinical trial design and cure strategies. Methods: Four cohortswith participantswhoinitiatedARTduring acute infection or during chronic infectionwere enrolled in a cross-sectional, noninterventional study.Viral reservoir was evaluated by the Intact Proviral DNA Assay (IPDA), the Total HIVDNA Assay (THDA) and the Quantitative Viral Outgrowth Assay (QVOA). Viral diversity and susceptibility to V3-glycan bNAbs were determined by genotyping of the viral envelope gene. Results: Participants who initiated ART during the acute Fiebig I-IV stages had lower level of total HIV DNA than participants who initiated ART during chronic infection whereas no difference was observed in intact HIV DNA or outgrowth virus. Participants who initiated ART during Fiebig I-IV also had lower viral diversity and appeared to have higher susceptibility to bNAbs than participants initiating ART during chronic infection. Conclusion: Individuals initiating ART during Fiebig I-IV had small viral reservoirs, low viral diversity, and high susceptibility to bNAbs, and would be an optimal target population for proof-of-concept HIV cure trials.

Both human respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause immune-mediated under-five acute respiratory infections (ARIs), but differences in their disease pathogenesis, if any, are not well-known. This study was undertaken to analyze the epidemiological and immunological features of RSV and hMPV infections. Nasopharyngeal aspirates from children (aged 2 months to 5 years) with ARI, presenting to our tertiary care center between December 2013 and March 2016, were subjected to real-time polymerase chain reaction for the detection of RSV and hMPV. Positive samples were analyzed for co-infection and cytokine levels. Of the 349 nasopharyngeal aspirates, RSV was detected in 40.68% (142/349), hMPV in 6.59% (23/349), and both in 1.4% (5/349). Co-infections were common, with rhinovirus being the most common co-offender. The demographic and clinical parameters of RSV- and hMPV-infected children were comparable. The MMP-9/TIMP-1 ratio was significantly higher in RSV-mediated ARI and IFN-γ in hMPV-mediated ARI. Both RSV and hMPV are common among North Indian children with ARI, and coinfections are common. Their clinical features are non-discriminatory, and molecular diagnosis should be utilized to ascertain their individual epidemiology. The differences in their immune-pathogenesis (MMP-9/TIMP-1 ratio in RSV and IFN-γ in hMPV) could serve as useful tools for developing newer drugs.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency and resultant hyperglycemia. Complex interactions of genetic and environmental factors trigger the onset of autoimmune mechanisms responsible for development of autoimmunity to β cell antigens and subsequent development of T1D. A potential role of virus infections has long been hypothesized, and growing evidence continues to implicate enteroviruses as the most probable triggering viruses. Recent studies have strengthened the association between enteroviruses and development of autoimmunity in T1D patients, potentially through persistent infections. Enterovirus infections may contribute to different stages of disease development. We review data from both human cohort studies and experimental research exploring the potential roles and molecular mechanisms by which enterovirus infections can impact disease outcome. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has resulted in a pandemic that has had widespread effects on human activities. The clinical presentation of severe COVID-19 includes a broad spectrum of clinical disease, most notably acute respiratory distress syndrome, cytokine release syndrome (CRS), multiorgan failure, and death. Direct viral damage and uncontrolled inflammation have been suggested as contributory factors in COVID-19 disease severity. The COVID-19 pandemic has emphasized the critical role of an effective host immune response in controlling a virus infection and demonstrated the devastating effect of immune dysregulation. Understanding the nature of the immune response to SARS-CoV-2 pathogenesis is key to developing effective treatments for COVID-19. Here, we describe the nature of the dysregulated host immune response in COVID-19, identify potential mechanisms involved in CRS, and discuss potential strategies that can be used to manage immune dysregulation in COVID-19. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Las vacunas son productos biológicos que contienen antígenos que buscan generar protección frente a una exposición real al mismo. En cuanto a su importancia, constituyen de las intervenciones más costo-efectivas en salud pública, siendo superadas únicamente por el agua potable. A grandes rasgos, podemos dividir las vacunas en vivas atenuadas e inactivadas; no obstante, el nuevo coronavirus ha producido la emergencia de plataformas innovadoras que utilizan mecanismos intracelulares y moleculares con el mismo objetivo de generar inmunidad. Discusión Se realizó una búsqueda sistemática de la literatura utilizando las bases de datos electrónicas PUBMED, SCOPUS y Web of Science. Todos los tipos de diseño de estudio fueron considerados, sin embargo, considerando los redactados en inglés o español. Se hace una revisión de la literatura presente sobre las plataformas existentes para generar inmunidad frente al coronavirus SARS-CoV-2 y se desarrolla cada una según su ruta y forma de acción en aquellas basadas en: subunidades proteicas, vector viral recombinante, ácidos nucleicos, virus inactivados, partículas virales y virus vivos atenuados. Conclusión Los mecanismos por los cuales dichas vacunas generan inmunogenicidad son diferentes, no obstante, la constante inserción de mutaciones por parte del virus siguen siendo un objeto de interés y preocupación por los investigadores. Palabras claves: SARS CoV-2, COVID-19, Vacunas, Mutagénesis.

Серед персистуючих внутрішньоклітинних агентів провідне місце за поширеністю посідає група герпесвірусів. Всесвітня організація охорони здоров’я (ВООЗ) застерігає світове співтовариство про небезпеку прихованої пандемії герпетичної інфекції. За даними ВООЗ, від 70 до 90 % населення світу інфіковано одним або декількома типами вірусу герпесу і у 50 % з них через відсутність стійкого імунітету щорічно спостерігаються рецидиви захворювання. До родини герпесвірусів, що виявлені у людини, належать віруси простого герпесу 1-го і 2-го типів, герпесу Zoster, цитомегалії, Епштейна — Барр, герпесу людини 6, 7, 8-го типів. Так, у патогенезі герпетичної інфекції 1-го і 2-го типів виділяють чотири основні фази: проникнення в клітини епітелію → проникнення в нервові закінчення і паравертебральні ганглії → елімінація вірусу з тканин і органів → реактивація вірусів простого герпесу і його переміщення до воріт інфекції. Герпетична і цитомегаловірусна інфекція, що належить до групи TORCH-інфекцій, є найпоширенішою причиною інфікування плода, що може спричинити народження дитини з вадами розвитку. Герпесвірусні інфекції зараховують до групи інфекцій, асоційованих із синдромом імунодефіциту людини, вважають частою причиною ураження центральної нервової системи і внутрішніх органів в осіб зі вторинним імунодефіцитом. Практично всі відомі зараз герпесвіруси людини здатні спричиняти ураження нервової системи. У зв’язку з цим герпесвірусні інфекції стали однією з провідних медико-соціальних проблем і набувають загальнодержавного значення.

Numerous studies have shown that viruses can utilize or manipulate ribosomal proteins to achieve viral protein biosynthesis and replication. In our recent studies using proteomics analysis of virus-infected cells, we found that ribosomal protein L18 (RPL18) was the highest up-regulated differentially expressed protein, along with the increasingly expressed viral proteins later in Newcastle disease virus (NDV) infection. However, the association of RPL18 with viral protein biosynthesis and NDV replication remains unclear. In this study, we found that the expression and transcription levels of RPL18 was reduced early in NDV infection but increased later in NDV infection. In addition, the presence of cytoplasmic NDV matrix (M) protein was responsible for the increased expression of RPL18 in both virus-infected cells and plasmid-transfected cells. Moreover, cytoplasmic M protein increased RPL18 expression in a dose-dependent manner, even though they did not interact with each other. Furthermore, siRNA-mediated knockdown of RPL18 or overexpression of RPL18 dramatically reduced or enhanced NDV replication by decreasing or increasing viral protein translation rather than viral RNA synthesis and transcription. Taken together, these results suggested that the increased expression of RPL18 might be associated with the physical clumping together of the M protein, which in turn promoted viral protein biosynthesis and NDV replication. RESEARCH HIGHLIGHTSThe increased expression of RPL18 is associated with the presence of cytoplasmic M protein.Cytoplasmic M protein increases RPL18 expression in a dose-dependent manner.Knockdown of RPL18 reduces NDV replication by decreasing viral protein translation.Overexpression of RPL18 enhances NDV replication by increasing viral protein translation.

34 men were examined, who after participating in the liquidation of the Chornobyl NPP accident developed non-alcoholic fatty liver disease. The state of antiviral defense was evaluated by the levels of immunoglobulin (Ig) G and IgM antibodies in the blood serum. In most patients with non-alcoholic steatohepatitis, who were Chornobyl NPP accident liquidators, antibodies of the IgG, but not IgM class to the persistent mixed infection with herpes simplex virus types 1 and 2, cytomegaly and Epstein-Barr were found. A positive correlation was established between the antibody titers to the herpes simplex virus types 1 and 2 (anti-HSV-1/2 IgG) and cytomegalovirus (anti-CMV IgG) (rs = 0.383, p = 0.040), as well as between the antibodies titers to the nuclear antigen of Epstein-Barr virus (anti-EBV NA IgG) and antibodies to core antigen of Epstein-Barr (anti-EBV VCA IgG) (rs = 0.584, p = 0.002) in patients with persistent mixed infection of these herpesviruses.

Coronaviruses are large group of enveloped viruses with unsegmented, single-stranded, positive-sense RNA as genetic material. These are collection related RNA viruses that cause diseases of economically important vertebrate viz. mammals and birds. In humans, these viruses cause respiratory tract infections that can range from asymptomatic to life threatening. The asymptomatic disease include very similar to some cases of the common cold, while other deadly varieties can cause SARS, MERS, and COVID-19. The SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus) are zoonotic origin and extremely pathogenic coronaviruses that can cause localized and worldwide outbreak. The novel Coronaviruses, COVID-19 posses a unique morphology. The outer surface of the virus bearing surface spike and reveled like crown hence being named corona virus. The mode of replication of the virus is very unique as it replicate through the generation of nested set of viral mRNA. The HCoV (Human coronavirus) cause respiratory complication with asymptomatic to life threatening outcomes. From the past 15 years we have witnessed appearance of two zoonotic, extremely pathogenic human corona viruses the: SARS-CoV and MERS-CoV.

This article provides information about the processes of airway remodeling in children with bronchial asthma. There are described the changes in the levels of matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase, transforming growth factor, autoantibodies to collagen type III, endothelin-1 in bronchial asthma in children, uninfected and infected with intracellular infections caused by herpes simplex virus types I–II, cytomegalovirus, Epstein-Barr virus, Сhlamydophila pneumoniae and Mycoplasma pneumoniae., В статье представлены сведения о процессах ремоделирования дыхательных путей при бронхиальной астме у детей. Описаны изменения уровней матричных металлопротеиназ, тканевого ингибитора матричных протеиназ, трансформирующего фактора роста, аутоантител к коллагену III типа, эндотелина-1 у детей с бронхиальной астмой, не инфицированных и инфицированных внутриклеточными инфекциями, вызванными вирусом простого герпеса І–ІІ типов, цитомегаловирусом, вирусом Эпштейна — Барр, Сhlamydophila pneumoniae и Mycoplasma pneumoniae., У статті представлені відомості про процеси ремоделювання дихальних шляхів при бронхіальній астмі. Описано зміни рівнів матричних металопротеїназ, тканинного інгібітора матричних протеїназ, трансформуючого фактора росту, аутоантитіл до колагену III типу, ендотеліну-1 у дітей із бронхіальною астмою, не інфікованих та інфікованих внутрішньоклітинними інфекціями, викликаними вірусом простого герпесу І–ІІ типів, цитомегаловірусом, вірусом Епштейна — Барр, Сhlamydophila pneumoniae і Mycoplasma pneumoniae.

Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen in family Togaviridae, genus Alphavirus. Although CHIKV is well known for its ability to cause debilitating rheumatoid-like arthritis, it has been also been observed to cause cardiovascular symptoms such as arrhythmias. Here, using samples from a previous study, we sequenced RNA from serum, kidney, skeletal muscle, and cardiac muscle from CHIKV- and mock-infected IFN-αR−/− mice using two sequencing techniques to investigate heart-specific changes in virus mutational profiles and host gene expression. Mutation rates were similar across muscle tissues although heart tissue carried heart-specific CHIKV minority variants, one of which had a coding change in the nsP3 gene and another in the 3′UTR. Importantly, heart-specific transcriptional changes included differential expression of genes critical for ion transport and muscle contraction. These results demonstrate that CHIKV replicates in the hearts of immunodeficient mice and induce heart-specific mutations and host responses with implications for cardiac pathologies.

The ubiquitously-expressed proteolytic enzyme furin is closely related to the pathogenesis of SARS-CoV-2 and therefore represents a key target for antiviral therapy. Based on bioinformatic analysis and pseudovirus tests, we discovered a second functional furin site located in the spike protein. Furin still increased the infectivity of mutated SARS-CoV-2 pseudovirus in 293T-ACE2 cells when the canonical polybasic cleavage site (682–686) was deleted. However, K814A mutation eliminated the enhancing effect of furin on virus infection. Furin inhibitor prevented infection by 682–686-deleted SARS-CoV-2 in 293T-ACE2-furin cells, but not the K814A mutant. K814A mutation did not affect the activity of TMPRSS2 and cathepsin L but did impact the cleavage of S2 into S2′ and cell–cell fusion. Additionally, we showed that this functional furin site exists in RaTG13 from bat and PCoV-GD/GX from pangolin. Therefore, we discovered a new functional furin site that is pivotal in promoting SARS-CoV-2 infection.

Monoclonal antibodies are emerging as a viable treatment for the coronavirus disease 19 (COVID-19). However, newly evolved variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can reduce the efficacy of currently available antibodies and can diminish vaccine-induced immunity. Here, we demonstrate that the microscopic dynamics of neutralizing monoclonal antibodies can be profoundly modified by the mutations present in the spike proteins of the SARS-COV-2 variants currently circulating in the world population. The dynamical perturbations within the antibody structure, which alter the thermodynamics of antigen recognition, are diverse and can depend both on the nature of the antibody and on the spatial location of the spike mutation. The correlation between the motion of the antibody and that of the spike receptor binding domain (RBD) can also be changed, modulating binding affinity. Using protein-graph-connectivity networks, we delineated the mutant-induced modifications in the information-flow along allosteric pathway throughout the antibody. Changes in the collective dynamics were spatially distributed both locally and across long-range distances within the antibody. On the receptor side, we identified an anchor-like structural element that prevents the detachment of the antibodies; individual mutations there can significantly affect the antibody binding propensity. Our study provides insight into how virus neutralization by monoclonal antibodies can be impacted by local mutations in the epitope via a change in dynamics. This realization adds a new layer of sophistication to the efforts for rational design of monoclonal antibodies against new variants of SARS-CoV2, taking the allostery in the antibody into consideration.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered enteric coronavirus. We have previously shown that the caspase-dependent FASL-mediated and mitochondrion-mediated apoptotic pathways play a central role in SADS-CoV-induced apoptosis, which facilitates viral replication. However, the roles of intracellular signaling pathways in SADS-CoV-mediated cell apoptosis and the relative advantages that such pathways confer on the host or virus remain largely unknown. In this study, we show that SADS-CoV induces the activation of ERK during infection, irrespective of viral biosynthesis. The knockdown or chemical inhibition of ERK1/2 significantly suppressed viral protein expression and viral progeny production. The inhibition of ERK activation also circumvented SADS-CoV-induced apoptosis. Taken together, these data suggest that ERK activation is important for SADS-CoV replication, and contributes to the virus-mediated changes in host cells. Our findings demonstrate the takeover of a particular host signaling mechanism by SADS-CoV and identify a potential approach to inhibiting viral spread.

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, it became evident that the SARS-CoV-2 virus infects multiple organs including the brain. Several clinical studies revealed that patients with COVID-19 infection experience an array of neurological signs ranging in severity from headaches to life-threatening strokes. Although the exact mechanism by which the SARS-CoV-2 virus directly impacts the brain is not fully understood, several theories have been suggested including direct and indirect pathways induced by the virus. One possible theory is the invasion of SARS-CoV-2 to the brain occurs either through the bloodstream or via the nerve endings which is considered to be the direct route. Such findings are based on studies reporting the presence of viral material in the cerebrospinal fluid and brain cells. Nevertheless, the indirect mechanisms, including blood-clotting abnormalities and prolonged activation of the immune system, can result in further tissue and organ damages seen during the course of the disease. This overview attempts to give a thorough insight into SARS-CoV-2 coronavirus neurological infection and highlights the possible mechanisms leading to the neurological manifestations observed in infected patients.

Epstein-Barr virus (EBV) is associated with hematologic and solid tumors. In this study, we utilized a hybridization capture-based next generation sequencing (NGS) platform that targets 400 genes associated with hematological malignancies to detect and quantify non-targeted viral-derived EBV reads that aligned to the EBV reference contig (NC_007605). We evaluated 5,234 samples from 3,636 unique patients with hematological neoplasms and found that 100 samples (1.9%) in 93 unique patients had ≥ 6 EBV reads (range, 6-32,325; mean, 827.5; median, 54). The majority (n=73, 73%) represented known EBV-associated conditions, and the most common was post-transplant lymphoproliferative disorders (n=21, 29%). Documented EBV viremia accounted for a moderate quantity of EBV reads in 4/27 samples corresponding to conditions not known to be EBV-associated, while suspected viremia or low-level activation was likely the etiology in the remaining 23 samples. A good correlation (Spearman r=0.8, 95% CI 0.74-0.85) was found between EBV reads by NGS and systematic semi-quantitative EBER ISH assessment in 162 available samples, particularly at higher level of EBV-involvement. An optimal threshold for significant morphologic EBV-involvement was found to be ≥10 reads by the receiver operating characteristic (ROC) analysis (AUC 0.990 and 95% CI 0.9974-1.000%). Thus, in addition to mutational analysis, hybrid-capture-based NGS panels can be used to detect and quantitate off-target EBV-derived viral DNA, which correlates well with morphology.

Background Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD). Methods This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed. Results Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate. Conclusions Our findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF.

Nora virus is a RNA picorna-like virus that produces a persistent infection in Drosophila melanogaster. The genome is approximately 12,300 bases and is divided into four open reading frames (ORFs). Structurally, there are four important viral proteins: VP3, VP4A, VP4B, and VP4C. Three proteins (VP4A, VP4B, and VP4C) that form the virion's capsid are encoded by ORF 4, which produces a polyprotein that is post-translationally cleaved. The fourth protein (VP3) is encoded by ORF 3 and it is hypothesized to play a role in virion stability. The genes for these proteins were individually cloned into Escherichia coli, expressed, and the proteins were purified. Virus-like particles (VLPs) were assembled in vitro by mixing the proteins together in different combinations and measured via electron microscopy. Assemblies that contained VP4A and/or VP3 created VLPs with similar sizes to purified empty Nora virus capsids, potentially indicating that VP4A and/or VP3 are vital for Nora virus capsid structure, assembly, and/or stability. Not only does this study provide insight into the role of Nora virus proteins, but it may also lead to a deeper understanding of how Nora virus or other picorna-like viruses undergo assembly. Keywords: RNA viruses; Nora virus; picorna-like virus; virus-like particles; capsid assembly.

La enfermedad por coronavirus de 2019 (COVID-19) es una emergencia sanitaria pública global con numerosas facetas clínicas que incluyen renopatía aguda y enfermedad cerebrovascular aguda. Es necesario un conocimiento adicional de su mecanismo patogénico. Los trastornos de coagulación están claramente incluidos en dichos mecanismos. La gammapatía monoclonal se caracteriza por la sobreproducción de inmunoglobulina monoclonal causada por proliferación clonal. Utilizando un estudio postmortem de biopsias básicas percutáneas ecoguiadas, el objetivo de este informe es presentar nuestras observaciones sobre la patología del síndrome respiratorio agudo severo por infección de coronavirus 2 (SARS-CoV2) con gammapatía monoclonal. La presentación clínica fue insuficiencia renal aguda. Los hallazgos patológicos revelaron nefropatía por depósito de cadenas ligeras kappa. La inmunohistoquímica de SARS-CoV-2 fue positiva en ciertas células tubulares renales. La presencia de megacariocitos alveolares (alta densidad) fue un hallazgo notable, que explica probablemente el resultado final del paciente (enfermedad cerebrovascular aguda). El estudio inmunohistoquímico frente a SARS-CoV-2 no verifica el efecto patogénico del virus y, por tanto, su contribución a la nefropatía aguda.