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. We report that compounds 2 and 3 display a broad-spectrum antiviral activity, being able to effectively inhibit several strains of Influenza Viruses (IV), SARS-CoV-2 Delta and, to some extent, Herpes Simplex Virus 2 (HSV-2). Interestingly, the mechanism of action differs for each virus. We observed both a direct virucidal and a cell-mediated effect against IV, with a high barrier to antiviral resistance; a restricted cell-mediated mechanism of action against SARS-CoV-2 Delta and a direct virustatic activity against HSV-2. Of note, while the effect was lost against IV in tissue culture models of human airway epithelia, the antiviral activity was confirmed in this relevant model for SARS-CoV-2 Delta. Our results suggest that stilbene dimer derivatives are good candidate models for the treatment of enveloped virus infections.

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. In this study, we first evaluated the virucidal activity of methylene blue against influenza virus H1N1 upon different incubation times and in the presence or absence of light activation, and then against SARS-CoV-2. We further assessed the therapeutic activity of methylene blue by administering it to cells previously infected with SARS-CoV-2. Finally, we examined the effect of co-administration of the drug together with immune serum. Our findings reveal that methylene blue displays virucidal preventive or therapeutic activity against influenza virus H1N1 and SARS-CoV-2 at low micromolar concentrations and in the absence of UV-activation. We also confirm that MB antiviral activity is based on several mechanisms of action as the extent of genomic RNA degradation is higher in presence of light and after long exposure. Our work supports the interest of testing methylene blue in clinical studies to confirm a preventive and/or therapeutic efficacy against both influenza virus H1N1 and SARS-CoV-2 infections.

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. The membrane has outstanding efficacy against a broad range of viruses, which include enveloped, non-enveloped, airborne and waterborne viruses, such as SARS-CoV-2, H1N1 (the influenza A virus strain responsible for the swine flu pandemic in 2009) and enterovirus 71 (a non-enveloped virus resistant to harsh conditions, such as highly acidic pH), which highlights a possible role in fighting the current and future viral outbreaks and pandemics.

Host-Viral Infection Maps Reveal Signatures of Severe COVID-19 Patients.

Viruses are a constant threat to global health as highlighted by the current COVID-19 pandemic. Currently, lack of data underlying how the human host interacts with viruses, including the SARS-CoV-2 virus, limits effective therapeutic intervention. We introduce Viral-Track, a computational method that globally scans unmapped single-cell RNA sequencing (scRNA-seq) data for the presence of viral RNA, enabling transcriptional cell sorting of infected versus bystander cells. We demonstrate the sensitivity and specificity of Viral-Track to systematically detect viruses from multiple models of infection, including hepatitis B virus, in an unsupervised manner. Applying Viral-Track to bronchoalveloar-lavage samples from severe and mild COVID-19 patients reveals a dramatic impact of the virus on the immune system of severe patients compared to mild cases. Viral-Track detects an unexpected co-infection of the human metapneumovirus, present mainly in monocytes perturbed in type-I interferon (IFN)-signaling. Viral-Track provides a robust technology for dissecting the mechanisms of viral-infection and pathology.