Cholenamide-based, antiviral fluorescent probes targeting oxysterol-binding protein.

Oxysterols (OSs) represent a large family of cholesterol-derived molecules, involved in several physiological and pathological processes. Recently, we reported the remarkable antiviral activity against herpes simplex virus 2 (HSV-2) infection of three cholenamide or homocholenamide derivatives, namely PFM067, PFM064, and PFM069, identified by the screening of an in-house library of OS derivatives. With the aim to shed light on the antiviral mechanism of action of this class of molecules, we assumed to exploit the use of cholenamide-based fluorescent probes.

Efficient wastewater sample filtration improves the detection of SARS-CoV-2 variants: An extensive analysis based on sequencing parameters.

During the SARS-CoV-2 pandemic, many countries established wastewater (WW) surveillance to objectively monitor the level of infection within the population. As new variants continue to emerge, it has become clear that WW surveillance is an essential tool for the early detection of variants. The EU Commission published a recommendation suggesting an approach to establish surveillance of SARS-CoV-2 and its variants in WW, besides specifying the methodology for WW concentration and RNA extraction.

Polyoxometalate exerts broad-spectrum activity against human respiratory viruses hampering viral entry.

Human respiratory viruses have an enormous impact on national health systems, societies, and economy due to the rapid airborne transmission and epidemic spread of such pathogens, while effective specific antiviral drugs to counteract infections are still lacking. Here, we identified two Keggin-type polyoxometalates (POMs), [TiWCoO] (TiWCo) and [TiPWO] (TiPW), endowed with broad-spectrum activity against enveloped and non-enveloped human respiratory viruses, i.e.

Identification of oxysterol synthetic analogs as a novel class of late-stage inhibitors of herpes simplex virus 2 replication.

Genital herpes, most frequently caused by herpes simplex virus 2 (HSV-2) infection, is one of the most prevalent sexually transmitted infections. The current rationale for the treatment of HSV-2 infection involves nucleoside analogs (e.g.

The role of bacteria and viruses in Behçet syndrome: Should we move towards new paradigms?

The etiological complexity of Behçet syndrome (BS), an immune-mediated rare form of vasculitis characterized by multi-organ involvement, is still elusive due to an incomplete understanding of the synergy between genetic susceptibility, environmental triggers, and an abnormal immune response. Long-standing theories regarding the origins of BS include the involvement of infectious organisms supporting an aberrant immunological response through different mechanisms, including molecular mimicry. Additionally, it has been demonstrated that the BS phenotypes are linked to oral and gut microbiome dysbiosis, which is a dynamic reservoir of millions of microbes containing proteins and metabolites that can mimic the autoantigens.

27-Hydroxycholesterol inhibits rhinovirus replication in vitro and on human nasal and bronchial histocultures without selecting viral resistant variants.

The genetic plasiticity of viruses is one of the main obstacles to the development of antivirals. The aim of this study has been to assess the ability of two physiologic oxysterols and host-targeting antivirals - namely 25- and 27-hydroxycholesterol (25OHC and 27OHC) - to select resistant strains, using human rhinovirus (HRV) as a challenging model of a viral quasispecies. Moreover, we selected 27OHC for further studies aimed at exploring its potential for the development of antiviral drugs.

Link between SARS-CoV-2 emissions and airborne concentrations: Closing the gap in understanding.

The airborne transmission of SARS-CoV-2 remains surprisingly controversial; indeed, health and regulatory authorities still require direct proof of this mode of transmission. To close this gap, we measured the viral load of SARS-CoV-2 of an infected subject in a hospital room (through an oral and nasopharyngeal swab), as well as the airborne SARS-CoV-2 concentration in the room resulting from the person breathing and speaking. Moreover, we simulated the same scenarios to estimate the concentration of RNA copies in the air through a novel theoretical approach and conducted a comparative analysis between experimental and theoretical results.

Wastewater-based SARS-CoV-2 environmental monitoring for Piedmont, Italy.

The experience gained over the last hundred years clearly indicates that two groups of viruses represent the main risk for the development of highly transmissible epidemics and pandemics in the human species: influenza viruses and coronaviruses (CoV). Although the search for viruses with pandemic potential in the environment may have an important predictive and monitoring role, it is still based on empirical methodologies, mostly resulting from the clinic and not fully validated for environmental matrices. As far as the SARS-CoV-2 pandemic, currently underway, is concerned, environmental monitoring activities aiming at checking the presence of SARS-CoV-2 in wastewater can be extremely useful to predict and check the diffusion of the disease.

SARS-CoV-2 airborne transmission: A validated sampling and analytical method.

The airborne transmission path for SARS-CoV-2 is of primary scientific and health-related interest as it could actually involve management, accessibility, use and functionality of many activities, including hospitals), schools, workplaces, factories, transport, sport venues and outdoor environment. It is necessary to develop a sampling and analytical method for virus-laden bioaerosol that could be considered reliable and validated according to ISO/IEC 17025 requirements. The present paper defines sample pretreatments aiming at recover SARS-CoV-2 from glass-fiber and PTFE filters employed by low and high-volume air samplers.

Trend of 25-hydroxycholesterol and 27-hydroxycholesterol plasma levels in patients affected by active chronic hepatitis B virus infection and inactive carriers.

Hepatitis B virus (HBV) infection is a global health problem with different immunological phases and therapeutic approaches. The serological condition of inactive carrier (IC) was recently well defined as a clinical and virological stable status, in which specific treatment is usually deferred, while the active chronic hepatitis B (CHB) condition requires an immediate treatment strategy. Recently, a possible broad antiviral effect of oxysterols, in particular 25-hydroxycholesterol (25OHC) and 27-hydroxycholesterol (27OHC), was observed, as most likely linked to the positive modulation of innate immunity, but no clear evidence is available about their possible role in chronic HBV infection.

SARS-CoV-2 and indoor/outdoor air samples: a methodological approach to have consistent and comparable results.

Since the beginning of coronavirus disease 2019 (COVID-19) pandemic, large attention has been focused on the relationship between SARS-CoV-2 diffusion and environment. As a matter of fact, clear evidence of the transmission of SARS-CoV-2 via respiratory aerosol would be of primary importance; at the same time, checking the presence of SARS-CoV-2 in wastewater can be extremely useful to control the diffusion of the disease. Up to now, many studies report SARS-CoV-2 concentrations in indoor/outdoor air samples or water/wastewater samples that can differ by order of magnitude.

Effect of industrial processing and storage procedures on oxysterols in milk and milk products.

Oxysterols are products of enzymatic and/or chemical cholesterol oxidation. While some of the former possess broad antiviral activities, the latter mostly originate from the deterioration of the nutritional value of foodstuff after exposure to heat, light, radiation and oxygen, raising questions about their potential health risks. We evaluated the presence of selected oxysterols in bovine colostrum and monitored the evolution of their cholesterol ratio throughout an entire industrial-scale milk production chain and after industrially employed storage procedures of milk powders.

Anti-Zika virus and anti-Usutu virus activity of human milk and its components.

The benefits of human milk are mediated by multiple nutritional, trophic, and immunological components, able to promote infant's growth, maturation of its immature gut, and to confer protection against infections. Despite these widely recognized properties, breast-feeding represents an important mother-to-child transmission route of some viral infections. Different studies show that some flaviviruses can occasionally be detected in breast milk, but their transmission to the newborn is still controversial.

Punica granatum Leaf Ethanolic Extract and Ellagic Acid as Inhibitors of Zika Virus Infection.

Zika virus, an arthropod-borne flavivirus, is an emerging healthcare threat worldwide. Zika virus is responsible for severe neurological effects, such as paralytic Guillain-Barrè syndrome, in adults, and also congenital malformations, especially microcephaly. No specific antiviral drugs and vaccines are currently available, and treatments are palliative, but medicinal plants show great potential as natural sources of anti-Zika phytochemicals.

The cholesterol metabolite 27-hydroxycholesterol inhibits SARS-CoV-2 and is markedly decreased in COVID-19 patients.

There is an urgent need to identify antivirals against the coronavirus SARS-CoV-2 in the current COVID-19 pandemic and to contain future similar emergencies early on. Specific side-chain cholesterol oxidation products of the oxysterols family have been shown to inhibit a large variety of both enveloped and non-enveloped human viral pathogens. Here we report on the in vitro inhibitory activity of the redox active oxysterol 27-hydroxycholesterol against SARS-CoV-2 and against one of the common cold agents HCoV-OC43 human coronavirus without significant cytotoxicity.

Acyclovir-loaded sulfobutyl ether-β-cyclodextrin decorated chitosan nanodroplets for the local treatment of HSV-2 infections.

Acyclovir is the gold standard drug for herpes simplex virus type 2 (HSV-2) infection treatment. Vaginal topical therapy with acyclovir is hampered due to its poor bioavailability, low retention at the vaginal mucosa, thus requiring high doses and frequent administrations. Nanocarriers have been proposed to overcome the challenges associated with antiviral delivery.

Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro.

Breast milk is a complex biofluid that nourishes infants, supports their growth and protects them from diseases. However, at the same time, breastfeeding is a transmission route for human cytomegalovirus (HCMV), with preterm infants being at a great risk of congenital disease. The discrepancy between high HCMV transmission rates and the few reported cases of infants with severe clinical illness is likely due to the protective effect of breast milk.

Antiviral oxysterols are present in human milk at diverse stages of lactation.

Oxysterols are cholesterol oxidation derivatives. Those containing an additional hydroxyl group on the side chain of the cholesterol molecule result from a physiological enzymatic synthesis and include the majority of oxysterols present in the circulation. Among these, 25-hydroxycholesterol (25OHC) and 27-hydroxycholesterol (27OHC) are characterized by a broad antiviral activity and are now considered involved in the innate immune response against viruses.

Colostrum from cows immunized with a veterinary vaccine against bovine rotavirus displays enhanced in vitro anti-human rotavirus activity.

Human rotaviruses represent a major cause of severe diarrheal disease in infants and young children. The limited impact of oral vaccines on global estimates of rotavirus mortality and the suboptimal use of oral rehydration justify the need for alternative prophylactic and therapeutic strategies, especially for immunocompromised hosts. The protective effects of colostrum-the first milk produced during the initial 24 to 48 h after parturition-are well documented in the literature.

Anti-zika virus activity of polyoxometalates.

Zika virus (ZIKV) is an emerging infectious viral pathogen associated with severe fetal cerebral anomalies and the paralytic Guillain-Barrè syndrome in adults. It was the cause of a recent global health crisis following its entrance into a naïve population in the Americas. Nowadays, no vaccine or specific antiviral against ZIKV is available.

Novel broad spectrum virucidal molecules against enveloped viruses.

Viral infections are an important cause of death worldwide. Unfortunately, there is still a lack of antiviral drugs or vaccines for a large number of viruses, and this represents a remarkable challenge particularly for emerging and re-emerging viruses. For this reason, the identification of broad spectrum antiviral compounds provides a valuable opportunity for developing efficient antiviral therapies.

High Temperature-Short Time Pasteurization Has a Lower Impact on the Antiviral Properties of Human Milk Than Holder Pasteurization.

Holder pasteurization (62. 5°C for 30 min) is recommended by all international human milk bank guidelines to prevent infections potentially transmitted by donor human milk. A drawback is that it affects some human milk bioactive and nutritive components.