Insights into the specificity for the interaction of the promiscuous SARS-CoV-2 nucleocapsid protein N-terminal domain with deoxyribonucleic acids.

The SARS-CoV-2 nucleocapsid protein (N) is a multifunctional promiscuous nucleic acid-binding protein, which plays a major role in nucleocapsid assembly and discontinuous RNA transcription, facilitating the template switch of transcriptional regulatory sequences (TRS). Here, we dissect the structural features of the N protein N-terminal domain (N-NTD) and N-NTD plus the SR-rich motif (N-NTD-SR) upon binding to single and double-stranded TRS DNA, as well as their activities for dsTRS melting and TRS-induced liquid-liquid phase separation (LLPS). Our study gives insights on the specificity for N-NTD(-SR) interaction with TRS. We observed an approximation of the triple-thymidine (TTT) motif of the TRS to ß-sheet II, giving rise to an orientation difference of ~25° between dsTRS and non-specific sequence (dsNS). It led to a local unfavorable energetic contribution that might trigger the melting activity. The thermodynamic parameters of binding of ssTRSs and dsTRS suggested that the duplex dissociation of the dsTRS in the binding cleft is entropically favorable. We showed a preference for TRS in the formation of liquid condensates when compared to NS. Moreover, our results on DNA binding may serve as a starting point for the design of inhibitors, including aptamers, against N, a possible therapeutic target essential for the virus infectivity.

Movember in a pandemic - it matters, more than ever.

Dear Editor, in recent years there has been an increase in the number of new cases of cancer. This increase, in part, is closely related to the increase in average life expectancy, as well as more accurate diagnostic techniques and well-defined screening programs. [...].

[Persons with disabilities during the COVID-19 pandemic: guaranteeing fundamental rights and equity in care]. / Pessoas com deficiência na pandemia da COVID-19: garantia de direitos fundamentais e equidade no cuidado.

This is a scoping review of the PubMed, Scopus, BIREME, SciELO, and Web of Science databases, including publications from December 2019 to May 2020 with the objective of identifying and systematizing the literature on the status of persons with disabilities in the initial months of the COVID-19 pandemic. The review aimed to search for original peer-reviewed articles published in indexed journals, in addition to the specialized gray literature. We reviewed 386 texts and included 33 articles and documents in the study. The review's results pointed to three thematic categories that reflect the main discussions on the theme in the literature: vulnerabilities of persons with disabilities during the pandemic; rights of persons with disabilities in this context; and protective measures and access to information on COVID-19 for persons with disabilities. In the context of the public health emergency, historically marginalized communities such as persons with disabilities run the risk of feeling more vulnerable, suffering deprivations, discrimination in screening plans for care, and prejudices and stigmas that influence decision-making in healthcare and exacerbate preexisting inequalities, making this group more susceptible to illness and lack of social protection. Although persons with disabilities have been acknowledged as a risk group for COVID-19, governments have been slow to develop plans to fight COVID-19 for this population. Few studies have attempted to understand the effects of the COVID-19 pandemic on persons with disabilities, especially in the sense of implementing measures in prevention, control, and protection that guarantee equity in care.

Este trabalho é uma revisão de escopo realizada nas bases de dados PubMed, Scopus, BIREME, SciELO e Web of Science, que incluiu publicações de dezembro de 2019 a maio de 2020, com o objetivo de identificar e sistematizar a literatura sobre a situação das pessoas com deficiência nos primeiros meses da pandemia da COVID-19. A revisão foi orientada para a busca de artigos originais, publicados em revistas indexadas e revisados por pares, além de literatura cinzenta especializada. Foram revisados 386 textos e incluídos no estudo 33 artigos e documentos. O resultado da revisão apontou três categorias temáticas que refletem as principais discussões apresentadas na literatura sobre o tema: vulnerabilidades das pessoas com deficiência diante da pandemia; direitos das pessoas com deficiência nesse contexto; e medidas de proteção e acesso à informação sobre COVID-19 voltadas para pessoas com deficiência. No contexto de emergência em saúde pública, comunidades historicamente marginalizadas, como as pessoas com deficiência, correm o risco de se sentirem mais vulneráveis, bem como sofrerem privações e discriminação nos planos de triagem de atendimento, além de preconceitos e estigmas que influenciam nas tomadas de decisão na assistência em saúde e intensificam desigualdades preexistentes, tornando esse grupo mais suscetível ao adoecimento e à desproteção social. Embora as pessoas com deficiência tenham sido reconhecidas como grupo de risco para COVID-19, houve um atraso, por parte dos governos, na construção de planos de enfrentamento à doença para essa população. São escassos estudos para a compreensão dos efeitos da pandemia da COVID-19 nas pessoas com deficiência, especialmente no sentido da efetivação de medidas de prevenção, controle e proteção que garantam a equidade no cuidado.

Se trata de una revisión de alcance, realizada en las bases de datos PubMed, Scopus, BIREME, SciELO y Web os Science, incluyendo publicaciones de diciembre de 2019 a mayo de 2020, con el objetivo de identificar y sistematizar la literatura sobre la situación de las personas con discapacidad durante los primeros meses de la pandemia de la COVID-19. La revisión se orientó hacia la búsqueda de artículos originales, publicados en revistas indexadas y revisados por pares, además de literatura gris especializada. Se revisaron 386 textos y se incluyeron en el estudio 33 artículos y documentos. El resultado de la revisión apuntó tres categorías temáticas que reflejan las principales discusiones presentadas en la literatura sobre el tema: vulnerabilidades de las personas con discapacidad ante la pandemia; derechos de las personas con discapacidad en ese contexto; y medidas de protección y acceso a la información sobre COVID-19, dirigidas a las personas con discapacidad. En el contexto de emergencia en salud pública, comunidades históricamente marginalizadas, como las personas con discapacidad, corren el riesgo de que se sientan más vulnerables, sufran privaciones, discriminación en los ámbitos de clasificación de atención, además de que padezcan prejuicios y estigmas que influencian en las tomas de decisión en la asistencia en salud e intensifican desigualdades preexistentes, haciendo este grupo más susceptible a la enfermedad y a la desprotección social. Pese a que las personas con discapacidad hayan sido reconocidas como grupo de riesgo para la COVID-19, hubo un atraso, por parte de los gobiernos, en la construcción de planes de lucha contra la COVID-19 para esta población. Son escasos los estudios para la comprensión de los efectos de la pandemia de la COVID-19 en las personas con discapacidad, especialmente en el sentido de la efectivización de medidas de prevención, control y protección que garanticen la equidad en el cuidado.

Through DNA sensors and hidden mitochondrial effects of SARS-CoV-2.

The COVID-19 pandemic brought attention to studies about viral infections and their impact on the cell machinery. SARS-CoV-2, for example, invades the host cells by ACE2 interaction and possibly hijacks the mitochondria. To better understand the disease and to propose novel treatments, crucial aspects of SARS-CoV-2 enrolment with host mitochondria must be studied. The replicative process of the virus leads to consequences in mitochondrial function, and cell metabolism. The hijacking of mitochondria, on the other hand, can drive the extrusion of mitochondrial DNA (mtDNA) to the cytosol. Extracellular mtDNA evoke robust proinflammatory responses once detected, that may act in different pathways, eliciting important immune responses. However, few receptors are validated and are able to detect and respond to mtDNA. In this review, we propose that the mtDNA and its detection might be important in the immune process generated by SARS-CoV-2 and that this mechanism might be important in the lung pathogenesis seen in clinical symptoms. Therefore, investigating the mtDNA receptors and their signaling pathways might provide important clues for therapeutic interventions.

Metabolic Alterations in SARS-CoV-2 Infection and Its Implication in Kidney Dysfunction.

Clinical strategies focusing on pathogen elimination are expected in an infectious-disease outbreak, such as the severe coronavirus disease 2019 (COVID-19), to avoid organ dysfunction. However, understanding the host response to viral infection is crucial to develop an effective treatment to optimize the patient's conditions. The pathogenic viruses can promote metabolic changes during viral infection, favoring its survival, altering cell phenotype and function, and causing sustained inflammation and tissue injury. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, provokes systemic and cell metabolic changes and possibly altering lipid and glucose metabolism. Besides severe acute respiratory syndrome (SARS), SARS-CoV-2 can cause acute kidney injury, which has been associated with the severity of the disease. Although it is not clear the mechanisms whereby SARS-CoV-2 induces kidney dysfunction, it is known that the virus presents kidney tropism, namely, podocytes and proximal tubular epithelial cells. Changes in renal cell metabolism and systemic metabolic disorders are important events in kidney injury progression. Here, we explored the metabolism and its interface with SARS-CoV-2 infection and raised the perspective on metabolism disturbances as a critical event to kidney dysfunction in COVID-19.