Virus adaptation to heparan sulfate comes with capsid stability tradeoff.

Because of high mutation rates, viruses constantly adapt to new environments. When propagated in cell lines, certain viruses acquire positively charged amino acids on their surface proteins, enabling them to utilize negatively charged heparan sulfate (HS) as an attachment receptor. In this study, we used enterovirus A71 (EV-A71) as model and demonstrated that unlike the parental MP4 variant, the cell-adapted strong HS-binder MP4-97R/167G does not require acidification for uncoating and releases its genome in the neutral or weakly acidic environment of early endosomes.

Development of Broad-Spectrum β-Cyclodextrins-Based Nanomaterials Against Influenza Viruses.

In recent decades, epidemics and pandemics have multiplied throughout the world, with viruses generally being the primary responsible agents. Among these, influenza viruses play a key role, as they potentially cause severe respiratory distress, representing a major threat to public health. Our study aims to develop new broad-spectrum antivirals against influenza to improve the response to viral disease outbreaks.

Enhancing pulmonary delivery and immunomodulation of respiratory diseases through virus-mimicking nanoparticles.

This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycol-coated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 ± 24 nm, a neutral zeta potential, osmolarity of 358 ± 28 mOsmol/kg, and a pH of 6.

Non-Steroidal Estrogens Inhibit Influenza Virus by Interacting with Hemagglutinin and Preventing Viral Fusion.

Influenza virus is one of the main causes of respiratory infections worldwide. Despite the availability of seasonal vaccines and antivirals, influenza virus infections cause an important health and economic burden. Therefore, the need to identify alternative antiviral strategies persists.

ANGPTL4 is a potential driver of HCV-induced peripheral insulin resistance.

Chronic hepatitis C (CHC) is associated with the development of metabolic disorders, including both hepatic and extra-hepatic insulin resistance (IR). Here, we aimed at identifying liver-derived factor(s) potentially inducing peripheral IR and uncovering the mechanisms whereby HCV can regulate the action of these factors. We found ANGPTL4 (Angiopoietin Like 4) mRNA expression levels to positively correlate with HCV RNA (r = 0.

Antiviral properties of trans-δ-viniferin derivatives against enveloped viruses.

Over the last century, the number of epidemics caused by RNA viruses has increased and the current SARS-CoV-2 pandemic has taught us about the compelling need for ready-to-use broad-spectrum antivirals. In this scenario, natural products stand out as a major historical source of drugs. We analyzed the antiviral effect of 4 stilbene dimers [1 (trans-δ-viniferin); 2 (11',13'-di-O-methyl-trans-δ-viniferin), 3 (11,13-di-O-methyl-trans-δ-viniferin); and 4 (11,13,11',13'-tetra-O-methyl-trans-δ-viniferin)] obtained from plant substrates using chemoenzymatic synthesis against a panel of enveloped viruses.

Variant enterovirus A71 found in immune-suppressed patient binds to heparan sulfate and exhibits neurotropism in B-cell-depleted mice.

Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease outbreaks with neurological complications and deaths. We previously isolated an EV-A71 variant in the stool, cerebrospinal fluid, and blood of an immunocompromised patient who had a leucine-to-arginine substitution on the VP1 capsid protein, resulting in increased heparin sulfate binding. We show here that this mutation increases the virus's pathogenicity in orally infected mice with depleted B cells, which mimics the patient's immune status, and increases susceptibility to neutralizing antibodies.

Altered cell function and increased replication of rhinoviruses and EV-D68 in airway epithelia of asthma patients.

Introduction: Rhinovirus (RV) infections constitute one of the main triggers of asthma exacerbations and an important burden in pediatric yard. However, the mechanisms underlying this association remain poorly understood.

Methods: In the present study, we compared infections of reconstituted airway epithelia originating from asthmatic versus healthy donors with representative strains of RV-A major group and minor groups, RV-C, RV-B, and the respiratory enterovirus EV-D68.

Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting.

SARS-CoV-2 is currently causing an unprecedented pandemic. While vaccines are massively deployed, we still lack effective large-scale antiviral therapies. In the quest for antivirals targeting conserved structures, we focused on molecules able to bind viral RNA secondary structures.

An anti-influenza combined therapy assessed by single cell RNA-sequencing.

Influenza makes millions of people ill every year, placing a large burden on the healthcare system and the economy. To develop a treatment against influenza, we combined virucidal sialylated cyclodextrins with interferon lambda and demonstrated, in human airway epithelia, that the two compounds inhibit the replication of a clinical H1N1 strain more efficiently when administered together rather than alone. We investigated the mechanism of action of the combined treatment by single cell RNA-sequencing analysis and found that both the single and combined treatments impair viral replication to different extents across distinct epithelial cell types.

Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting.

SARS-CoV-2 is currently causing an unprecedented pandemic. While vaccines are massively deployed, we still lack effective large-scale antiviral therapies. In the quest for antivirals targeting conserved structures, we focused on molecules able to bind viral RNA secondary structures.

Polyanionic Amphiphilic Dendritic Polyglycerols as Broad-Spectrum Viral Inhibitors with a Virucidal Mechanism.

Heparin has been known to be a broad-spectrum inhibitor of viral infection for almost 70 years, and it has been used as a medication for almost 90 years due to its anticoagulant effect. This nontoxic biocompatible polymer efficiently binds to many types of viruses and prevents their attachment to cell membranes. However, the anticoagulant properties are limiting their use as an antiviral drug.

Sequential infections with rhinovirus and influenza modulate the replicative capacity of SARS-CoV-2 in the upper respiratory tract.

Although frequently reported since the beginning of the pandemic, questions remain regarding the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interaction with circulating respiratory viruses in coinfected patients. We here investigated dual infections involving early-pandemic SARS-CoV-2 and the Alpha variant and three of the most prevalent respiratory viruses, rhinovirus (RV) and Influenza A and B viruses (IAV and IBV), in reconstituted respiratory airway epithelial cells cultured at air-liquid interface. We found that SARS-CoV-2 replication was impaired by primary, but not secondary, rhino- and influenza virus infection.

: A Small but Versatile Species.

Enteroviruses (EVs) from the D species are the causative agents of a diverse range of infectious diseases in spite of comprising only five known members. This small clade has a diverse host range and tissue tropism. It contains types infecting non-human primates and/or humans, and for the latter, they preferentially infect the eye, respiratory tract, gastrointestinal tract, and nervous system.

Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro.

Methylene blue is an FDA (Food and Drug Administration) and EMA (European Medicines Agency) approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment.

Interferon Lambda Delays the Emergence of Influenza Virus Resistance to Oseltamivir.

Influenza viruses are a leading cause of morbidity and mortality worldwide. These air-borne pathogens are able to cross the species barrier, leading to regular seasonal epidemics and sporadic pandemics. Influenza viruses also possess a high genetic variability, which allows for the acquisition of resistance mutations to antivirals.

An antiviral trap made of protein nanofibrils and iron oxyhydroxide nanoparticles.

Minimizing the spread of viruses in the environment is the first defence line when fighting outbreaks and pandemics, but the current COVID-19 pandemic demonstrates how difficult this is on a global scale, particularly in a sustainable and environmentally friendly way. Here we introduce and develop a sustainable and biodegradable antiviral filtration membrane composed of amyloid nanofibrils made from food-grade milk proteins and iron oxyhydroxide nanoparticles synthesized in situ from iron salts by simple pH tuning. Thus, all the membrane components are made of environmentally friendly, non-toxic and widely available materials.

Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo.

Influenza is one of the most widespread viral infections worldwide and represents a major public health problem. The risk that one of the next pandemics is caused by an influenza strain is high. It is important to develop broad-spectrum influenza antivirals to be ready for any possible vaccine shortcomings.

Modeling Poliovirus Infection Using Human Engineered Neural Tissue Enriched With Motor Neuron Derived From Embryonic Stem Cells.

Poliomyelitis is caused by poliovirus (PV), a positive strand non-enveloped virus. Since its discovery in the 1950s, several cell culture and molecular methods have been developed to detect and characterize the various strains of PV. Here, we provide an accurate and standardized protocol to differentiate human embryonic stem cells (hESCs) toward engineered neural tissue enriched with motor neurons (MN ENTs).

RSV and HMPV Infections in 3D Tissue Cultures: Mechanisms Involved in Virus-Host and Virus-Virus Interactions.

Respiratory viral infections constitute a global public health concern. Among prevalent respiratory viruses, two pneumoviruses can be life-threatening in high-risk populations. In young children, they constitute the first cause of hospitalization due to severe lower respiratory tract diseases.