SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity.

Circulating bat coronaviruses represent a pandemic threat. However, our understanding of bat coronavirus pathogenesis and transmission potential is limited by the lack of phenotypically characterized strains. We created molecular clones for the two closest known relatives of SARS-CoV-2, BANAL-52 and BANAL-236. We demonstrated that BANAL-CoVs and SARS-CoV-2 have similar replication kinetics in human bronchial epithelial cells. However, BANAL-CoVs have impaired replication in human nasal epithelial cells and in the upper airway of mice. We also observed reduced pathogenesis in mice and diminished transmission in hamsters. Further, we observed that diverse bat coronaviruses evade interferon and downregulate major histocompatibility complex class I. Collectively, our study demonstrates that despite high genetic similarity across bat coronaviruses, prediction of pandemic potential of a virus necessitates functional characterization. Finally, the restriction of bat coronavirus replication in the upper airway highlights that transmission potential and innate immune restriction can be uncoupled in this high-risk family of emerging viruses.

Exploring TRIM proteins' role in antiviral defense against influenza A virus and respiratory coronaviruses.

Numerous tripartite motif (TRIM) proteins, identified as E3 ubiquitin ligases, participate in various viral infections through ubiquitylation, ISGylation, and SUMOylation processes. Respiratory viruses, particularly influenza A virus (IAV) and respiratory coronaviruses (CoVs), have severely threatened public health with high morbidity and mortality, causing incalculable losses. Research on the regulation of TRIM proteins in respiratory virus infections is crucial for disease prevention and control. This review introduces TRIM proteins, summarizes recent discoveries regarding their roles and molecular mechanisms in IAV and CoVs infections, discusses current research gaps, and explores potential future trends in this rapidly developing field. It aims to enhance understanding of virus-host interactions and inform the development of new molecularly targeted therapies.

Anti-RBD IgG antibodies from endemic coronaviruses do not protect against the acquisition of SARS-CoV-2 infection among exposed uninfected individuals.

Background: The Coronaviridae family comprises seven viruses known to infect humans, classified into alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1), which are considered endemic. Additionally, it includes SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome), and the novel coronavirus SARS-CoV-2, responsible for COVID-19. SARS-CoV-2 induces severe respiratory complications, particularly in the elderly, immunocompromised individuals and those with underlying diseases. An essential question since the onset of the COVID-19 pandemic has been to determine whether prior exposure to seasonal coronaviruses influences immunity or protection against SARS-CoV-2. Methods: In this study, we investigated a cohort of 47 couples (N=94), where one partner tested positive for SARS-CoV-2 infection via real-time PCR while the other remained negative. Plasma samples, collected at least 30 days post-PCR reaction, were assessed using indirect ELISA and competition assays to measure specific antibodies against the receptor-binding domain (RBD) portion of the Spike (S) protein from SARS-CoV-2, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1. Results: IgG antibody levels against the four endemic coronavirus RBD proteins were similar between the PCR-positive and PCR-negative individuals, suggesting that IgG against endemic coronavirus RBD regions was not associated with protection from infection. Moreover, we found no significant IgG antibody cross-reactivity between endemic coronaviruses and SARS-CoV-2 RBDs. Conclusions: Taken together, results suggest that anti-RBD antibodies induced by a previous infection with endemic HCoVs do not protect against acquisition of COVID-19 among exposed uninfected individuals.

An inactivated PDCoV vaccine induces robust neutralizing antibodies and immune protection in pigs lasting for three months.

Porcine deltacoronavirus (PDCoV), a novel enteropathogenic coronavirus, causes diarrhea mainly in suckling piglets and has the potential to infect humans. Whereas, there is no commercially available vaccine which can effectively prevent this disease. In this study, to ascertain the duration of immune protection of inactivated PDCoV vaccine, suckling piglets were injected subcutaneously with inactivated PDCoV vaccine using a prime/boost strategy at 3 and 17-day-old. Neutralizing antibody assay showed that the level of the inactivated PDCoV group was still ≥1:64 at three months after prime vaccination. The three-month-old pigs were orally challenged with PDCoV strain CZ2020. Two pigs in challenge control group showed mild to severe diarrhea at 10-11 day-post-challenge (DPC), while the inactivated PDCoV group had no diarrhea. High levels of viral shedding, substantial intestinal villus atrophy, and positive straining of viral antigens in ileum were detected in challenge control group, while the pigs in inactivated PDCoV group exhibited significantly reduced viral load, minor intestinal villi damage and negative straining of viral antigens. These results demonstrated that PDCoV was pathogenic against three-month-old pigs and inactivated PDCoV vaccine can provide effective protection in pigs lasting for three months.

CovEpiAb: a comprehensive database and analysis resource for immune epitopes and antibodies of human coronaviruses.

Coronaviruses have threatened humans repeatedly, especially COVID-19 caused by SARS-CoV-2, which has posed a substantial threat to global public health. SARS-CoV-2 continuously evolves through random mutation, resulting in a significant decrease in the efficacy of existing vaccines and neutralizing antibody drugs. It is critical to assess immune escape caused by viral mutations and develop broad-spectrum vaccines and neutralizing antibodies targeting conserved epitopes. Thus, we constructed CovEpiAb, a comprehensive database and analysis resource of human coronavirus (HCoVs) immune epitopes and antibodies. CovEpiAb contains information on over 60 000 experimentally validated epitopes and over 12 000 antibodies for HCoVs and SARS-CoV-2 variants. The database is unique in (1) classifying and annotating cross-reactive epitopes from different viruses and variants; (2) providing molecular and experimental interaction profiles of antibodies, including structure-based binding sites and around 70 000 data on binding affinity and neutralizing activity; (3) providing virological characteristics of current and past circulating SARS-CoV-2 variants and in vitro activity of various therapeutics; and (4) offering site-level annotations of key functional features, including antibody binding, immunological epitopes, SARS-CoV-2 mutations and conservation across HCoVs. In addition, we developed an integrated pipeline for epitope prediction named COVEP, which is available from the webpage of CovEpiAb. CovEpiAb is freely accessible at https://pgx.zju.edu.cn/covepiab/.

Phosphorylation of G3BP1 is involved in the regulation of PDCoV-induced inflammatory response.

Stress granules (SGs), the main component is GTPase-activating protein-binding protein 1 (G3BP1), which are assembled during viral infection and function to sequester host and viral mRNAs and proteins, are part of the antiviral responses. In this study, we found that porcine deltacoronavirus (PDCoV) infection induced stable formation of robust SGs in cells through a PERK (protein kinase R-like endoplasmic reticulum kinase)-dependent mechanism. Overexpression of SGs marker proteins G3BP1 significantly reduced PDCoV replication in vitro, while inhibition of endogenous G3BP1 enhanced PDCoV replication. Moreover, PDCoV infected LLC-PK1 cells raise the phosphorylation level of G3BP1. By overexpression of the G3BP1 phosphorylated protein or the G3BP1 dephosphorylated protein, we found that phosphorylation of G3BP1 is involved in the regulation of PDCoV-induced inflammatory response. Taken together, our study presents a vital aspect of the host innate response to invading pathogens and reveals attractive host targets for antiviral target.

Differences and similarities between innate immune evasion strategies of human coronaviruses.

So far, seven coronaviruses have emerged in humans. Four recurring endemic coronaviruses cause mild respiratory symptoms. Infections with epidemic Middle East respiratory syndrome-related coronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-1 are associated with high mortality rates. SARS-CoV-2 is the causative agent of the coronavirus disease 2019 pandemic. To establish an infection, coronaviruses evade restriction by human innate immune defenses, such as the interferon system, autophagy and the inflammasome. Here, we review similar and distinct innate immune manipulation strategies employed by the seven human coronaviruses. We further discuss the impact on pathogenesis, zoonotic emergence and adaptation. Understanding the nature of the interplay between endemic/epidemic/pandemic coronaviruses and host defenses may help to better assess the pandemic potential of emerging coronaviruses.

O impacto da covid - 19 na saúde de pessoas institucionalizadas / The impact of COVID-19 on the health of institutionalized persons / El impacto del COVID-19 em la salude de las personas institucionalizada

Introdução:A população idosa constitui um dos grupos mais vulneráveis à infecção pelo novo coronavírus. Tal fragilidade é ainda mais evidente naqueles que residem em Instituições para Idosos, por apresentar maior risco de contaminação e, ainda, de morbimortalidade. Objetivo: Identificar o impacto da COVID-19 na saúde de pessoas idosas residentes nas Instituições de Longa Permanência. Metodologia:Trata-se de estudo retrospectivo de revisão integrativa da literatura, entre os meses de novembro/2020 e março/2021, sintetizando estudos publicados sobre a temática. A partir do objetivo traçado para este estudo, determinamos quais seriam as questões norteadoras: 1. "Quais medidas estão sendo adotadas para minimizar os efeitos da COVID-19 nas Instituições de Longa Permanência para Idosos?" 2. "Quais os principais impactos causados por essas medidas?". Estes eixos colaboram para a compreensão dos acontecimentos de significativa relevância social. Resultados:As instituições para idosos, como ambientes coletivos, possuem residentes com elevada vulnerabilidade à infecção pelo novo coronavírus. Naqueles idosos acometidos por quadros de demência e outras doenças neurológicas, o isolamento social aprofunda a gravidade da infecção pela COVID-19, dificultando, assim, as atividades relacionadas à atenção e assistência realizadas pelos cuidadores. Ademais, caracteriza-se como medida fundamental a adoção do rastreamento laboratorial precoce para potencializar a prevenção de casos e promover o controle da infecção. Percebe-se ainda uma deficiência referente à construção de um protocolo com medidas de profilaxia e manejo adequado de modo mais direcionado dentro dessas instituições. Conclusão:Torna-se urgente um olhar mais atento às necessidades da população idosa, especialmente dogrupo institucionalizado, de modo a promover políticas de investimento em cuidados de saúde integrais e realizados por equipe multiprofissional (AU).

Introduction:The elderly population is one of the groups most vulnerable to infection by the new coronavirus. Such fragility is even more evident in those who live in Institutions for the Aged, as it presents a higher risk of contamination and, even, of morbidity and mortality. Objective: To identify the impact of COVID-19 on the health of elderly people residing in Long Term Institutions for the Aged. Methodology:This is a retrospective study of integrative literature review, between the months of November/2020 and March/2021, synthesizing published studies on the theme. Based on the objective outlined for this study, we determined what the guiding questions would be: 1. "What measures are being taken to minimize the effects of COVID-19 on Long Term Care Institutions for the Aged?" 2. "What are the main impacts caused by these measures?. These axes contribute to the understanding of events of significant social relevance. Results:Institutions for the aged, as collective environments, have residents with high vulnerability to infection with the new coronavirus. In those aged people affected by dementia and other neurological diseases, social isolation deepens the severity of the infection by COVID-19, thus hampering the activities related to the care and assistance performed by caregivers. In addition, the adoption of early laboratory screening is characterized as a fundamental measure to enhance the prevention of cases and promote infection control. It is also perceived a deficiency regarding the construction of a protocol with prophylaxis measures and adequate management in a more targeted way within these institutions.Conclusions:It is urgent to look more closely at the needs of the aged population, especially the institutionalized group, in order to promote investment policies in comprehensive health care carried out by a multidisciplinary team (AU).

Introducción: la población anciana es uno de los grupos más vulnerables a la infección por el nuevo coronavirus. Tal fragilidad es aún más evidente en quienes viven en Instituciones de Ancianos, ya que presenta un mayor riesgo de contaminación e, incluso, de morbilidad y mortalidad. Objetivo: Identificar el impacto del COVID-19 en la salud de los ancianos que residen en Instituciones de Atención de Larga Duración. Metodología: Se trata de un estudio retrospectivo de revisión integradora de la literatura, entre los meses de noviembre/2020 y marzo/2021, sintetizando los estudios publicados sobre el tema. Con base en el objetivo delineado para este estudio, determinamos cuáles serían las preguntas orientadoras: 1. "¿Qué medidas se están tomando para minimizar los efectos del COVID-19 en las Instituciones de Atención de Larga Duración para el Anciano?" 2. "¿Cuáles son los principales impactos provocados por estas medidas?". Estos ejes contribuyen a la comprensión de hechos de relevancia social significativa.Resultados:Las instituciones para los ancianos, como entornos colectivos, tienen residentes conalta vulnerabilidad a la infección por el nuevo coronavirus. Aquellos ancianos afectados por demencia y otras enfermedades neurológicas, el aislamiento social profundiza la gravedad de la infección por COVID-19, dificultando así las actividades relacionadas con el cuidado y asistencia que realizan los cuidadores. Además, la adopción del cribado precoz de laboratorio se caracteriza por ser una medida fundamental para potenciar la prevención de casos y promover el control de infecciones. También se percibe una deficiencia en la construcción de un protocolo con medidas de profilaxis y manejo adecuado de manera más focalizada dentro de estas instituciones. Conclusiones: Es urgente mirar más de cerca las necesidades de la población anciana, especialmente del grupo institucionalizado, para promover políticas de inversión en la atención integral de salud llevadas a cabo por un equipo multidisciplinario (AU).

Determine the Dentists' Practice in Compliance with General and Guidelines for Handling Coronavirus Disease 2019: A Systematic Review and Meta-analysis

ABSTRACT Objective: To determine the Dentists' practice in compliance with general and guidelines for handling Coronavirus Disease 2019. Material and Methods: PubMed, Embase, ISI, Scopus, Medicine have been used to search for articles until September 2020. EndNote X9 was used to manage electronic resources as a resource. Joanna Briggs Institute reviewer's manual (JBI) tools was used to assess the quality of studies included in the current systematic and meta-analysis review. The 95% confidence interval (CI) effect size, the random effect model, and the Restricted maximum-likelihood (REML) methods have all been calculated. I2 values of more than 50% indicated moderate-to-high heterogeneity. Stata/MP v.16 (the fastest version of Stata) statistical software was used to evaluate the Meta-analysis. Results: 39 articles were found in the initial keyword search. The full text of 16 studies was reviewed, and six studies were selected in the end. 72% of participants used a face mask during the dental procedure (72%, 95% CI; 40%-100%). 63% of participants measured fever when patients arrived during the COVID-19 pandemic (63%, 95% CI; 46%-79%). Moreover, 72% of participants used a face mask during the dental procedure (72%, 95% CI; 40%-100%). According to JBI tools, all studies had a moderate risk of bias. Conclusion: The results show that the performance of dental professionals in the conditions of the COVID-19 epidemic is not favorable. Training should be under the standards of treatment guidelines and further measures so that dental professionals can show proper practice by increasing their awareness of this virus and following up on its infection.

COVID-19-Related Challenges in Dental Education: Experiences From Brazil, the USA, and Australia

Abstract Objective: To describe and compare how three dental schools from different countries (Australia, Brazil, and the USA) have managed experiences in dental education during the COVID-19 crisis. Material and Methods: It is a descriptive study reporting the experience that three distinct dental schools faced during the COVID-19 pandemic. They represent countries that adopted different measures to tackle the pandemic and were undergoing different stages of the disease. Results: After the WHO declared the COVID-19 pandemic, the Federal University of Paraíba suspended all on-site teaching, research, and service activities. For the return to teaching activities, the use of information and communications technology resources for distance learning was recommended. At the School of Dental Medicine (University of Pittsburgh), all research activities were suspended or, otherwise, could not be interrupted because of the employment of unique materials or supplies. When the pandemic started, Australia was one of the first countries to introduce strong regulations related to social distancing, travel restrictions, testing and tracking of infected patients. As such, the universities started to be closed from mid-March, cancelling all clinical and pre-clinical activities, maintaining online theoretical activities, such as seminars, lectures, and journal clubs. Conclusion: Numerous and critical difficulties have arisen as a result of the pandemic for individuals, communities and institutions that will have long-lasting effects. Our students face disruption to their education and career; our professional colleagues will be challenged rebuilding their practices, while staff at all Dental Schools are experiencing various hardships.

Viral research in Brazilian owls (Tyto alba and Rhinoptynx clamator) by transmission electron microscopy / Investigación viral en buhos brasileños (Tyto alba y Rhinoptynx clamator) a través de microscopía electrónica de transmisión

The barn-owl (Tyto Alba) and striped-owl (Rhinoptynx clamator) belong respectively to the families Tytonidae and Strigidae. Avian paramyxoviruses have been isolated from a variety of species of wild and domestic birds wordlwide causing diverse clinical symptoms and signs. Paramyxoviruses belong to the family Paramyxoviridae and Avulovirus genus, including nine serotypes (APMV 1 to 9). The lymphoid leukosis is a retrovirus-induced neoplasia. The avian retroviruses belong to the Retroviridae family and to the Alpharetrovirus genus. Coronaviruses can cause respiratory and enteric disease in several species of birds. They belong to the Coronaviridae family and to the groups 3a e 3c. In this study, we describe the presence of viruses in four owls, two barn owls (Tyto alba) and two striped owls (Rhinoptynx clamator), rescued from tree-lined streets of Sao Paulo, Brazil and sent to the Recovery Center of Wild Animals of the Tietê Ecological Park, where the animals died. Fragments of lung, liver and small intestine of these birds were processed for transmission electron microscopy utilizing negative staining (rapid preparation), immunoelectron microscopy and immunocitochemistry techniques. Under the transmission electron microscopy paramyxovirus particles, pleomorphic, roughly spherical or filamentous, measuring 100 to 500 nm of diameter containing an envelope covered by spikes, an herring-bone helical nucleocapsid-like structure, measuring 15 to 20 nm in diameter, were visualized in the samples of lung, liver and small intestine of all owls. In small intestine samples of the two striped-owl (owls 3 and 4) it was detected pleomorphic coronavirus particles with a diameter of 75-160 nm containing a solar corona-shaped envelope, with projections of approximately 20 nm of diameter. In liver fragments of one striped-owl (owl 4) pleomorphic particles of retrovirus with a diameter of 80-145 nm containing an envelope with short projections and diameter of 9 nm were....

La lechuza (Tyto Alba) y el búho de orejas (Rhinoptynx clamator) pertenecen respectivamente a las familias Strigidae y Tytonidae. El paramixovirus aviario se ha aislado de especies de vida silveste como las aves domésticas por todo el mundo, causando diversos síntomas clínicos. El paramixovirus pertenece a la familia Paramyxoviridae y al Avulovirus genus que incluye nueve serotipos (APMV 1 a 9). La leucosis linfoide es una neoplasia inducida por retrovirus. Los retrovirus aviarios pertenecen a la familia Retroviridae y el género Alpharetrovirus. Los coronavirus pueden causar enfermedades respiratorias y entéricas en varias especies de aves. Ellos pertenecen a la familia Coronaviridae y a los grupos 3a y 3c. En este estudio, se describe la presencia del virus en cuatro búhos, dos lechuzas (Tyto alba) y dos búhos de orejas (Rhinoptynx clamator), rescatados de las calles arboladas de São Paulo, Brasil y enviados al Centro de Recuperación de Animales Silvestres del Parque Ecológico de Tietê, donde hubo murieron los animales. Fragmentos de pulmón, delhígado y del intestino delgado de estas aves fueron procesados para microscopía electrónica de transmisión utilizando tinción negativa (preparación rápida), inmunomicroscopía y técnicas de inmunocitoquímica. Bajo microscopía electrónica de transmisión, partículas de paramixovirus, pleomórficas, aproximadamente esféricas o filamentosas, de 100 a 500 nm de diámetro con un sobre cubierto por espigas, y nucleocápside helicoidal con características de espiga, midiendo 15 a 20 nm de diámetro, fueron visualizadas en las muestras de pulmón, hígado e intestino delgado de todos los búhos. En muestras de intestino delgado de dos búho de orejas (búhos 3 y 4) se detectaron partículas pleomórficas con coronavirus de un diámetro de 75-160 nm con un sobre con forma de corona solar, con proyecciones de aproximadamente 20 nm de diámetro. En el hígado de un búho de orejas (búho 4) se observaron partículas pleomórficas de retrovirus con ...