Unraveling the complexities of neurotropic virus infection and immune evasion.

SUMMARYNeurotropic viruses, a diverse group of pathogens targeting the central nervous system (CNS), utilize multiple mechanisms to invade this highly protected compartment. These include hematogenous spread, retrograde axonal transport, and Trojan horse strategies, enabling viral entry and dissemination. Once within the CNS, these viruses interact with resident immune cells such as microglia and astrocytes, triggering type I interferon responses critical for antiviral defense.

First-in-class inhibitors of Nsp15 endoribonuclease of SARS-CoV-2: Modeling, synthesis, and enzymatic assay of thiazolidinedione and rhodanine analogs.

During infection, the coronavirus nonstructural protein 15 (Nsp15), a uridine-specific endoribonuclease, suppresses the host cell's antiviral response. Recently, researchers have paid more attention to this relatively underexplored yet potentially viable drug target. In this study, we employed FRET-based screening assays to identify potent Nsp15 inhibitors.

Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV.

Background: The pathogenic coronaviruses (CoVs) MERS-CoV and SARS-CoV-2, which are responsible for the MERS outbreak and the COVID-19 pandemic, respectively, continue to infect humans, with significant adverse outcomes. There is a continuing need to develop mucosal vaccines against these respiratory viral pathogens to prevent entry and replication at mucosal sites. The receptor-binding domain (RBD) of the CoV spike (S) protein is a critical vaccine target, and glycan masking is a unique approach for designing subunit vaccines with improved neutralizing activity.

SIRT2 suppresses aging-associated cGAS activation and protects aged mice from severe COVID-19.

Aging-associated vulnerability to coronavirus disease 2019 (COVID-19) remains poorly understood. Here, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected aged mice lacking SIRT2, a cytosolic NAD-dependent deacetylase, develop more severe disease and show increased mortality, while treatment with an NAD booster, 78c, protects aged mice from lethal infection. Mechanistically, we demonstrate that SIRT2 modulates the acetylation of cyclic GMP-AMP synthase (cGAS), an immune sensor for cytosolic DNA, and suppresses aging-associated cGAS activation and inflammation.

Lung inflammation drives Long Covid.

Peroxisome dysfunction in macrophages impairs lung repair after COVID-19 in mice.

Complement is primarily activated in the lung in a mouse model of severe COVID-19.

studies and observational human disease data suggest the complement system contributes to SARS-CoV-2 pathogenesis, although how complement dysregulation develops in severe COVID-19 is unknown. Here, using a mouse-adapted SARS-CoV-2 virus (SARS2-N501Y) and a mouse model of COVID-19, we identify significant serologic and pulmonary complement activation post-infection. We observed C3 activation in airway and alveolar epithelia, and pulmonary vascular endothelia.

Severe acute respiratory syndrome coronavirus 2 infection unevenly impacts metabolism in the coronal periphery of the lungs.

SARS-CoV-2, the virus responsible for COVID-19, is a highly contagious virus that can lead to hospitalization and death. COVID-19 is characterized by its involvement in the lungs, particularly the lower lobes. To improve patient outcomes and treatment options, a better understanding of how SARS-CoV-2 impacts the body, particularly the lower respiratory system, is required.

Cells that survive acute SARS-CoV-2 infection contribute to inflammation and lung regeneration in mice.

Unlabelled: Post-acute sequelae of COVID-19 involves several organs, but its basis remains poorly understood. Some infected cells in mice survive the acute infection and persist for extended periods in the respiratory tract but not in other tissues. Here, we describe two experimental models of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection to assess the effect of viral virulence on previously infected cells.

Imbalanced VWF-ADAMTS13 axis contributes to the detrimental impact of a preceding respiratory tract infection on stroke.

Respiratory tract infections (RTIs) caused by bacteria or viruses are associated with stroke severity. Recent studies have revealed an imbalance in the von Willebrand factor (VWF)-ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) axis in patients with RTIs, including coronavirus disease 2019. We examined whether this imbalance contributes to RTI-mediated stroke severity.

CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection.

Neutrophils, particularly low-density neutrophils (LDNs), are believed to contribute to acute COVID-19 severity. Here, we showed that neutrophilia can be detected acutely and even months after SARS-CoV-2 infection in patients and mice, while neutrophil depletion reduced disease severity in mice. A key factor in neutrophilia and severe disease in infected mice was traced to the chemokine CXCL12 secreted by bone marrow cells and unexpectedly, endothelial cells.

Respiratory syncytial virus infection provides protection against severe acute respiratory syndrome coronavirus challenge.

Unlabelled: Respiratory infections are a major health burden worldwide. Respiratory syncytial virus (RSV) is among the leading causes of hospitalization in both young children and older adults. The onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the public health response had a profound impact on the normal seasonal outbreaks of other respiratory viruses.

Mouse hepatitis virus JHMV I protein is required for maximal virulence.

encode a conserved accessory gene within the +1 open reading frame (ORF) of nucleocapsid called the internal N gene. This gene is referred to as "I" for mouse hepatitis virus (MHV), ORF9b for severe acute respiratory CoV (SARS-CoV) and SARS-CoV-2, and ORF8b for Middle East respiratory syndrome CoV (MERS-CoV). Previous studies have shown ORF8b and ORF9b have immunoevasive properties, while the only known information for MHV I is its localization within the virion of the hepatotropic/neurotropic A59 strain of MHV.

Structural basis for mouse receptor recognition by bat SARS2-like coronaviruses.

The animal origin of SARS-CoV-2 remains elusive, lacking a plausible evolutionary narrative that may account for its emergence. Its spike protein resembles certain segments of BANAL-236 and RaTG13, two bat coronaviruses considered possible progenitors of SARS-CoV-2. Additionally, its spike contains a furin motif, a common feature of rodent coronaviruses.

IL-13 decreases susceptibility to airway epithelial SARS-CoV-2 infection but increases disease severity in vivo.

Treatments available to prevent progression of virus-induced lung diseases, including coronavirus disease 2019 (COVID-19) are of limited benefit once respiratory failure occurs. The efficacy of approved and emerging cytokine signaling-modulating antibodies is variable and is affected by disease course and patient-specific inflammation patterns. Therefore, understanding the role of inflammation on the viral infectious cycle is critical for effective use of cytokine-modulating agents.

A confusion of pathways: Discerning cell death mechanisms in SARS-CoV-2 infection.

Upon SARS-CoV-2 infection, infected cells undergo necroptosis, whereas delayed apoptosis and pyroptosis occur in uninfected, bystander cells, thus providing a plausible explanation for the extensive injury among myriad uninfected cells.

SARS-CoV-2 infection unevenly impacts metabolism in the coronal periphery of the lungs.

COVID-19 significantly decreases amino acids, fatty acids, and most eicosanoidsSARS-CoV-2 preferentially localizes to central lung tissueMetabolic disturbance is highest in peripheral tissue, not central like viral loadSpatial metabolomics allows detection of metabolites not altered overallSARS-CoV-2, the virus responsible for COVID-19, is a highly contagious virus that can lead to hospitalization and death. COVID-19 is characterized by its involvement in the lungs, particularly the lower lobes. To improve patient outcomes and treatment options, a better understanding of how SARS-CoV-2 impacts the body, particularly the lower respiratory system, is required.

A Unique mRNA Vaccine Elicits Protective Efficacy against the SARS-CoV-2 Omicron Variant and SARS-CoV.

The highly pathogenic coronaviruses SARS-CoV-2 and SARS-CoV have led to the COVID-19 pandemic and SARS outbreak, respectively. The receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2, particularly the Omicron variant, has frequent mutations, resulting in the reduced efficiency of current COVID-19 vaccines against new variants. Here, we designed two lipid nanoparticle-encapsulated mRNA vaccines by deleting the mutant RBD of the SARS-CoV-2 Omicron variant (SARS2-S (RBD-del)) or by replacing this mutant RBD with the conserved and potent RBD of SARS-CoV (SARS2-S (SARS-RBD)).