The SARS-CoV-2 pandemic is not only a health crisis, but also shatters the socialand economic lives through regulations and social restrictions. As seen duringSARS 2002-2003, measures like social restrictions can impact behaviournegatively, leading to discrimination, stigmatisation and xenophobia. There is alack of studies on antisocial behaviour and crime during health crises, such aspandemics. Related studies on disaster and crime gave mixed results, with somesuggesting an increase in prosocial rather than antisocial behaviour. Using acriminological perspective, German news media from January 1, 2020 untilMarch 31, 2020 were analysed. These media sources were the tabloid Bild andtwo main elite newspapers, Süddeutsche Zeitung and Frankfurter AllgemeineZeitung. Analyses were conducted quantitatively based on frequencies, means andword counts. Additionally, a qualitative media content analysis regarding events,behaviour and story tone was undertaken. The aim was to reveal indications ofreported behavioural changes. For a complete overview, both antisocial andprosocial behaviours were included. Results indicate that antisocial behaviour,such as ignoring of governmental advice and rules, and discriminatory behaviours,as well as crimes like fraud became more prominent over time than prosocial andhelping behaviour. This study shows only a fragment of the situation in Germany,but highlights the importance of continuous assessments of human behaviourduring dynamic and critical times.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos, documentos técnicos y artículos en preprint actualizado al 22 de Abril de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos, artículos en preprint y noticias científicas actualizado al 23 de Abril de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos, artículos en preprint y revisiones sistemáticas actualizado al 24 de Abril de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos, revisiones sistemáticas y noticias científicas actualizado al 27 de Abril de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos y artículos preprint actualizados al 01 de Junio de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos y artículos preprint actualizados al 02 de Junio de 2020.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / SARS-CoV-2 main protease is a common target for inhibition assays due to its high conservation among coronaviruses. Since flavonoids show antiviral activity, several in silico works have proposed them as potential SARS-CoV-2 main protease inhibitors. Nonetheless, there is reason to doubt certain results given the lack of consideration for flavonoid promiscuity or main protease plasticity, usage of short library sizes, absence of control molecules and/or the limitation of the methodology to a single target site. Here, we report a virtual screening study where dorsilurin E, euchrenone a11, sanggenol O and CHEMBL2171598 are proposed to inhibit main protease through different pathways. Remarkably, novel structural mechanisms were observed after sanggenol O and CHEMBL2171598 bound to experimentally proven allosteric sites. The former drastically affected the active site, while the latter triggered a hinge movement which has been previously reported for an inactive SARS-CoV main protease mutant. The use of a curated database of 4.8 k flavonoids, combining two well-known docking software (AutoDock Vina and AutoDock4.2), molecular dynamics and MMPBSA, guaranteed an adequate analysis and robust interpretation. These criteria can be considered for future screening campaigns against SARS-CoV-2 main protease. / Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica / Revisión por pares

INTRODUCTION: SARS-CoV-2 is a novel virus from the coronavirus family that emerged in the Hubei province of China in December 2019 and rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared a global pandemic. Infection with SARS-CoV-2 causes coronavirus disease 19 (COVID19) which can be fatal. There is an obvious and pressing need for research surrounding SARS-CoV-2 that will aid in eradication of this pandemic. OBJECTIVE: The goal of this study was to absolve the dire need for small animal models of human disease that demonstrate hallmark pathological features of infection. Due to ethical and financial obstacles, the use of animals that closely resemble human immunity, such as non-human primates, is often not a viable option. For this reason, there is a push to develop small animal models that can mimic human disease responses, particularly those in viral infections that have a narrow species tropism. To achieve this in the context of the novel coronavirus, SARS-CoV-2, we studied various mouse models and their capacity to become infected with and mount an immune response to SARS-CoV-2. Our goal was to identify a model that sufficiently mimics severe COVID19 seen in humans as well as provide molecular insight into pathways that prevent the development of severe disease. METHODS: NRG-L and HIS-NRGF-L mice were subcutaneously implanted with human fetal lung xenografts and infected with SARS-CoV-2. Tissues were stained with H&E for histopathological scoring. NRG-L and HIS-NRGF-L tissues were fluorescently labeled using 2 different multiplex immunohistochemistry panels. Slides were digitized by a Vectra Polaris™ fluorescent whole slide scanner and digital analysis was completed using HALO™. Statistical analysis was conducted using GraphPad Prism™ 9.0.1. RESULTS: Infected NRG-L mice present extensive histopathological manifestations when compared to uninfected controls. Cumulative histology scores at both 2 and 7DPI were increased when compared to uninoculated fLX. Neutrophil influx, intra-airspace necrosis, capillary fibrin thrombi, and presence of syncytial cells were the most significant independent observations that contributed to the increased cumulative score. Together these findings indicate that fLX inoculated with SARS-CoV-2 faithfully recapitulate several features of diffuse alveolar damage (DAD) described in severe COVID-19. HIS-NRGF-L mice displayed decreased influx of neutrophils, intra-airway necrosis, and syncytial cells when compared to NRG-L fLX. Hemorrhage was decreased at both 2 and 7 DPI for HIS-NRGF-L fLX compared to NRG-L fLX. Cumulative histology scores were decreased in HIS-NRGF-L fLX at 7 DPI when compared to NRG-L fLX. Taken together these findings support the hypothesis that human myeloid and lymphoid infiltrates suppress or prevent the disparate host response observed in NRGL-L fLX that manifested in pronounced diffuse alveolar damage. CONCLUSION: Using digital image analysis of multiplex immunohistochemistry paired with semi-quantitative histopathological scoring, this study characterized important hallmark lesions observed in severe COVID19 as seen in small animal models. NRG-L and HIS-NRGF-L mice that are subcutaneously implanted with human fetal lung xenografts are susceptible to infection with SARS-CoV-2 and can produce severe and moderate disease phenotypes respectively. Co-engraftment with human fetal lung tissue and human immune system components in HIS-NRGF-L mice suppresses the divergent host response that is observed in NRG-L mice. For this reason, NRG-L mice engrafted with fLX are an ideal small animal model of severe COVID19, whereas HIS-NRGF-L mice severe as a valuable and informative model for deciphering molecular mechanisms driving severe COVID-19 that will serve as targets for therapeutic development.

This work details the inhibition of BACE1, BACE2, and SARS-CoV-2 3CLpro through several novel and potent protease inhibitors. Nanomolar potency of BACE1 and BACE2 is achieved with all tested inhibitors, and the S2 subsite has been identified as a BACE2 selectivity determinant. This is supported by the observation that the novel BACE2 mutant, BACE2 L246N, displays increased potency and selectivity over BACE1 against this peptidomimetic scaffold. Nanomolar to micromolar potency of SARS-CoV-2 3CLpro is achieved with the compounds tested in this study. Kinetic data illustrates the allowed substitutions at the P1’, P1, P2, and P4 positions on two scaffolds: ML188 and GC376. Finally, this work presents the high-resolution crystal structures of four inhibitors bound to BACE1 and 12 inhibitors bound to SARS-CoV-2 3CLpro. These structural data help to explain the selectivity determinants of BACE1 and BACE2 and further enable structure-based drug design against these two enzymes for the treatments of Alzheimer's Disease and Type II Diabetes, respectively. Additionally, these structural data illustrate the flexibility of the GC376 scaffold at the P3/P4 position, providing a structural rationale for the observed differences in potency across the different analogs. These structural data further enable structure-based drug design against SARS-CoV-2 3CLpro for the treatment of COVID-19.