Autophagy in Inflammatory Response against SARS-CoV-2

The coronavirus disease pandemic, which profoundly reshaped the world in 2019 (COVID-19), and is currently ongoing, has affected over 200 countries, caused over 500 million cumulative cases, and claimed the lives of over 6.4 million people worldwide as of August 2022. The causative agent is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Depicting this virus' life cycle and pathogenic mechanisms, as well as the cellular host factors and pathways involved during infection, has great relevance for the development of therapeutic strategies. Autophagy is a catabolic process that sequesters damaged cell organelles, proteins, and external invading microbes, and delivers them to the lysosomes for degradation. Autophagy would be involved in the entry, endo, and release, as well as the transcription and translation, of the viral particles in the host cell. Secretory autophagy would also be involved in developing the thrombotic immune-inflammatory syndrome seen in a significant number of COVID-19 patients that can lead to severe illness and even death. This review aims to review the main aspects that characterize the complex and not yet fully elucidated relationship between SARS-CoV-2 infection and autophagy. It briefly describes the key concepts regarding autophagy and mentions its pro- and antiviral roles, while also noting the reciprocal effect of viral infection in autophagic pathways and their clinical aspects.

Autophagy in Inflammatory Response against SARS-CoV-2.

The coronavirus disease pandemic, which profoundly reshaped the world in 2019 (COVID-19), and is currently ongoing, has affected over 200 countries, caused over 500 million cumulative cases, and claimed the lives of over 6.4 million people worldwide as of August 2022. The causative agent is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Depicting this virus' life cycle and pathogenic mechanisms, as well as the cellular host factors and pathways involved during infection, has great relevance for the development of therapeutic strategies. Autophagy is a catabolic process that sequesters damaged cell organelles, proteins, and external invading microbes, and delivers them to the lysosomes for degradation. Autophagy would be involved in the entry, endo, and release, as well as the transcription and translation, of the viral particles in the host cell. Secretory autophagy would also be involved in developing the thrombotic immune-inflammatory syndrome seen in a significant number of COVID-19 patients that can lead to severe illness and even death. This review aims to review the main aspects that characterize the complex and not yet fully elucidated relationship between SARS-CoV-2 infection and autophagy. It briefly describes the key concepts regarding autophagy and mentions its pro- and antiviral roles, while also noting the reciprocal effect of viral infection in autophagic pathways and their clinical aspects.

Differences in Perceived Stress between Genders among People with Diabetes during COVID Lockdown in Argentina

Many studies suggest that there is a difference in perceived stress (PS) among genders in general population. Gender differences in patients with diabetes are uncertain. Descriptions of gender differences in PS during Covid lockdown in people with diabetes are lacking. Objectives: To assess the differences regarding perceived stress and anxiety between genders among persons with diabetes during COVID-pandemic lockdown. Secondary: To describe the association between PS with metabolic control and other co-variables. Methods: Multicenter, cross-sectional observational study of data collection through an online survey. Adults with T1D and T2D in 37 Argentine Diabetes Centers were included, from April to May, 2020. Degree of stress was evaluated by the Perceived Stress Scale (PSS) , and anxiety by the Beck Anxiety Inventory (BAI) . Results: 2273 patients were included. 1194 (52.5%) were female. Age in woman 48.6 years and 52.1 in men. The proportion of patients with T2D was higher in male (58.6% vs. 48.9%) . Diabetes duration was around 14 years, similar in both genders. A1c levels were higher in female patients (7.7% vs. 7.5%, p < 0.05) . BAI and PPS scales resulted significantly correlated (r=0.58;p <0.001) . In the univariate analysis BAI and PPS scores were significantly higher in women with both T1D and T2D vs. men (BAI 8.9 vs. 6.6, p<0.001, PSS 14.3 vs. 11.8, p<0.001) . Using a logistic model as a discriminant function, female gender was significantly associated with BAI and PPS scores after adjustment for type of diabetes, age, A1c, educational level, living alone condition and the presence of comorbidities or complications (p<0.001) . Using multiple linear regression, BAI and PSS scores were significantly associated with female gender, after adjustment by the same covariates (BAI p<0.00 and PSS p<0.0013) . Conclusion: In the study sample, female gender was associated with higher scores of anxiety and PS, in a context of isolation due to COVID pandemic in Argentina.

Replication and single-cycle delivery of SARS-CoV-2 replicons.

Molecular virology tools are critical for basic studies of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and for developing new therapeutics. Experimental systems that do not rely on viruses capable of spread are needed for potential use in lower-containment settings. In this work, we use a yeast-based reverse genetics system to develop spike-deleted SARS-CoV-2 self-replicating RNAs. These noninfectious self-replicating RNAs, or replicons, can be trans-complemented with viral glycoproteins to generate replicon delivery particles for single-cycle delivery into a range of cell types. This SARS-CoV-2 replicon system represents a convenient and versatile platform for antiviral drug screening, neutralization assays, host factor validation, and viral variant characterization.

El COVID-19, las élites y el futuro de la economía política de la reducción de la desigualdad en América Latina

Existen diversas opiniones en la literatura sobre cómo repercuten las pandemias en la desigualdad de los ingresos. Mientras que en la literatura económica se sostiene que las pandemias aumentan la desigualdad, la literatura histórica y de las ciencias políticas señala que las pandemias podrían ocasionar quiebres institucionales y, en un contexto de cambios a nivel de las élites y de presiones desde los estratos más bajos, mantener las desigualdades. Tras examinar los datos actuales sobre las repercusiones de la enfermedad por coronavirus (COVID-19), hemos constatado que se están produciendo transferencias de los ingresos hacia las clases más altas y determinados cambios a nivel de las élites en la región. Sin embargo, dado que las élites han controlado las medidas económicas que se han adoptado para mitigar y enfrentar la crisis, hay pocos indicios de que se esté produciendo un quiebre institucional.

Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks.

The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of over one million people worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a member of the Coronaviridae family of viruses that can cause respiratory infections of varying severity. The cellular host factors and pathways co-opted during SARS-CoV-2 and related coronavirus life cycles remain ill defined. To address this gap, we performed genome-scale CRISPR knockout screens during infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E). These screens uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, sterol regulatory element-binding protein (SREBP) signaling, bone morphogenetic protein (BMP) signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VMP1, TMEM41, and TMEM64 (VTT) domain-containing protein transmembrane protein 41B (TMEM41B) for infection by SARS-CoV-2 and three seasonal coronaviruses. This human coronavirus host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics.

Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has devastated the global economy and claimed more than 1.7 million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen SARS-CoV-2 at two physiologically relevant temperatures along with three related coronaviruses (human coronavirus 229E [HCoV-229E], HCoV-NL63, and HCoV-OC43), allowing us to probe this interactome at a much higher resolution than genome-scale studies. This approach yielded several insights, including potential virus-specific differences in Rab GTPase requirements and glycosylphosphatidylinositol (GPI) anchor biosynthesis, as well as identification of multiple pan-coronavirus factors involved in cholesterol homeostasis. This coronavirus essentiality catalog could inform ongoing drug development efforts aimed at intercepting and treating coronavirus disease 2019 (COVID-19) and help prepare for future coronavirus outbreaks.