Marked neurotropism and potential adaptation of H5N1 clade 2.3.4.4.b virus in naturally infected domestic cats.

In April 2024, ten cats died in a rural South Dakota (SD) residence, showing respiratory and neurological symptoms. Necropsy and laboratory testing of two cats confirmed H5N1 clade 2.3.

Rapid evolution leads to extensive genetic diversification of cattle flu Influenza D virus.

Influenza D virus (IDV), the cattle flu virus, is a novel multi-host RNA virus, circulating silently worldwide, with widespread seropositivity among US cattle, reaching up to 80% in some areas raising a potential threat of cattle-to-human transmission. Currently, five genetic lineages of IDV have been described, but their evolutionary dynamics have not been studied. Although IDV was first identified in 2011, our comprehensive analysis of all known IDV genomes suggests that the earliest ancestors of IDV likely to have evolved towards the end of the 20 century and D/OK lineage appears to have emerged in 2005.

Enhanced Diversifying Selection on Polymerase Genes in H5N1 Clade 2.3.4.4b: A Key Driver of Altered Species Tropism and Host Range Expansion.

Highly pathogenic avian influenza H5N1 clade 2.3.4.

Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 Infection.

The pathologic consequences of Coronavirus Disease-2019 (COVID-19) include elevated inflammation and dysregulated vascular functions associated with thrombosis. In general, disruption of vascular homeostasis and ensuing prothrombotic events are driven by activated platelets, monocytes, and macrophages, which form aggregates (thrombi) attached to the endothelium lining of vessel walls. However, molecular pathways underpinning the pathological interactions between myeloid cells and endothelium during COVID-19 remain undefined.

Antiviral fibrils of self-assembled peptides with tunable compositions.

The lasting threat of viral pandemics necessitates the development of tailorable first-response antivirals with specific but adaptive architectures for treatment of novel viral infections. Here, such an antiviral platform has been developed based on a mixture of hetero-peptides self-assembled into functionalized β-sheets capable of specific multivalent binding to viral protein complexes. One domain of each hetero-peptide is designed to specifically bind to certain viral proteins, while another domain self-assembles into fibrils with epitope binding characteristics determined by the types of peptides and their molar fractions.

Dynamics of temporal immune responses in nonhuman primates and humans immunized with COVID-19 vaccines.

We assessed the humoral immune responses to a COVID-19 vaccine in a well-controlled rhesus macaque model compared to humans immunized with two mRNA vaccines over several months post-second dose. The plasma IgG levels against seven coronaviruses (including SARS-CoV-2) and antibody subtypes (IgG 1-4 and IgM) against SARS-CoV-2 were evaluated using multiplex assays. The neutralization capacity of plasma antibodies against the original SAR-CoV-2 isolate and nine variants was evaluated in vaccinated humans and non-human primates.

A phosphodiesterase-4 inhibitor reduces lung inflammation and fibrosis in a hamster model of SARS-CoV-2 infection.

Introduction: The Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection involves pulmonary inflammation that can progress to acute respiratory distress syndrome, a primary cause of lung damage/fibrosis in patients with Coronavirus Disease-2019 (COVID-19). Currently, there is no efficacious therapy available to alleviate lung fibrosis in COVID-19 cases. In this proof-of-concept study, we evaluated the effect of CC-11050, a small molecule phosphodiesterase-4 inhibitor, in dampening lung inflammation and fibrosis in a hamster model of SARS-CoV-2 infection.

Liposomal Glutathione Supplementation Mitigates Extrapulmonary Tuberculosis in the Liver and Spleen.

Background: Extrapulmonary tuberculosis (EPTB) accounts for a fifth of all () infections worldwide. The rise of multidrug resistance in alongside the hepatotoxicity associated with antibiotics presents challenges in managing and treating tuberculosis (TB), thereby prompting a need for new therapeutic approaches. Administration of liposomal glutathione (L-GSH) has previously been shown to lower oxidative stress, enhance a granulomatous response, and reduce the burden of in the lungs of -infected mice.

SARS-CoV-2 Prevalence and Variant Surveillance among Cats in Pittsburgh, Pennsylvania, USA.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects many mammals, and SARS-CoV-2 circulation in nonhuman animals may increase the risk of novel variant emergence. Cats are highly susceptible to SARS-CoV-2 infection, and there were cases of virus transmission between cats and humans. The objective of this study was to assess the prevalence of SARS-CoV-2 variant infection of cats in an urban setting.

Little Brown Bats () Support the Binding of SARS-CoV-2 Spike and Are Likely Susceptible to SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), believed to have originated from a bat species, can infect a wide range of non-human hosts. Bats are known to harbor hundreds of coronaviruses capable of spillover into human populations. Recent studies have shown a significant variation in the susceptibility among bat species to SARS-CoV-2 infection.

A SARS-CoV-2 Vaccine Designed for Manufacturability Results in Unexpected Potency and Non-Waning Humoral Response.

The rapid development of several highly efficacious SARS-CoV-2 vaccines was an unprecedented scientific achievement that saved millions of lives. However, now that SARS-CoV-2 is transitioning to the endemic stage, there exists an unmet need for new vaccines that provide durable immunity and protection against variants and can be more easily manufactured and distributed. Here, we describe a novel protein component vaccine candidate, MT-001, based on a fragment of the SARS-CoV-2 spike protein that encompasses the receptor binding domain (RBD).

SARS-CoV-2 Omicron (B.1.1.529) Infection of Wild White-Tailed Deer in New York City.

There is mounting evidence of SARS-CoV-2 spillover from humans into many domestic, companion, and wild animal species. Research indicates that humans have infected white-tailed deer, and that deer-to-deer transmission has occurred, indicating that deer could be a wildlife reservoir and a source of novel SARS-CoV-2 variants. We examined the hypothesis that the Omicron variant is actively and asymptomatically infecting the free-ranging deer of New York City.

Development and Validation of Indirect Enzyme-Linked Immunosorbent Assays for Detecting Antibodies to SARS-CoV-2 in Cattle, Swine, and Chicken.

Multiple domestic and wild animal species are susceptible to SARS-CoV-2 infection. Cattle and swine are susceptible to experimental SARS-CoV-2 infection. The unchecked transmission of SARS-CoV-2 in animal hosts could lead to virus adaptation and the emergence of novel variants.

L-GSH Supplementation in Conjunction With Rifampicin Augments the Treatment Response to in a Diabetic Mouse Model.

Both active tuberculosis (TB) and asymptomatic latent () infection (LTBI) cause significant health burdens to humans worldwide. Individuals with immunocompromising health conditions, such as Type 2 Diabetes Mellitus (T2DM), have a weakened ability to control infection and are more susceptible to reactivation of LTBI to active diseases. T2DM cases are known to have glutathione (GSH) deficiency and impaired immune cell function, including the granulomatous response to infection.

Comprehensive Analysis of Disease Pathology in Immunocompetent and Immunocompromised Hosts following Pulmonary SARS-CoV-2 Infection.

The Coronavirus disease 2019 (COVID-19) pandemic disproportionately affects immunocompetent and immunocompromised individuals, with the latter group being more vulnerable to severe disease and death. However, the differential pathogenesis of SARS-CoV-2 in the context of a specific immunological niche remains unknown. Similarly, systematic analysis of disease pathology in various extrapulmonary organs in immunocompetent and immunocompromised hosts during SARS-CoV-2 infection is not fully understood.

A CNN model for predicting binding affinity changes between SARS-CoV-2 spike RBD variants and ACE2 homologues.

The cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves the association of its receptor binding domain (RBD) with human angiotensin converting enzyme 2 (hACE2) as the first crucial step. Efficient and reliable prediction of RBD-hACE2 binding affinity changes upon amino acid substitutions can be valuable for public health surveillance and monitoring potential spillover and adaptation into non-human species. Here, we introduce a convolutional neural network (CNN) model trained on protein sequence and structural features to predict experimental RBD-hACE2 binding affinities of 8,440 variants upon single and multiple amino acid substitutions in the RBD or ACE2.

SARS-CoV-2, SARS-CoV, and MERS-CoV encode circular RNAs of spliceosome-independent origin.

Circular RNAs (circRNAs) are a newly recognized component of the transcriptome with critical roles in autoimmune diseases and viral pathogenesis. To address the importance of circRNA in RNA viral transcriptome, we systematically identified and characterized circRNAs encoded by the RNA genomes of betacoronaviruses using both bioinformatical and experimental approaches. We predicted 351, 224, and 2764 circRNAs derived from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus, respectively.

An intra-cytoplasmic route for SARS-CoV-2 transmission unveiled by Helium-ion microscopy.

SARS-CoV-2 virions enter the host cells by docking their spike glycoproteins to the membrane-bound Angiotensin Converting Enzyme 2. After intracellular assembly, the newly formed virions are released from the infected cells to propagate the infection, using the extra-cytoplasmic ACE2 docking mechanism. However, the molecular events underpinning SARS-CoV-2 transmission between host cells are not fully understood.

Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a rapidly evolving pandemic worldwide with at least 68 million COVID-19-positive cases and a mortality rate of about 2.2%, as of 10 December 2020. About 20% of COVID-19 patients exhibit moderate to severe symptoms.