Attività antivirale dell'estratto di mirtillo rosso e di epigallocatechin gallate contro virus altamente patogeni

Climate change, disruption of natural biotypes, and human population growth are contributing to the spread of an increasing number of emerging and re-emerging infectious diseases around the world, with a significant global economic burden. Infections are often associated with high mortality rates and/or long recovery periods. In humans, many of these emerging and re-emerging diseases are associated with virus spillover events from wildlife that cause unpredictable epidemics. For example, Ebola virus (EBOV) and rabies virus (RABV) are considered emerging viruses and cause a very serious disease with a high mortality rate. EBOV is a member of the Ebolavirus genus belonging to the Filoviridae family. EBOV is the etiological agent of Ebola virus disease (EVD), a hemorrhagic fever endemic in some African countries where the virus circulates in bat species causing epidemics in human and non-human primates. Infection to humans from animals occurs through contact with the body fluids of infected animals such as fruit bats, antelopes, chimpanzees, gorillas, dead or hunted and eaten without adequate cooking. The virus can subsequently spread within a human population through direct contact with the blood or body fluids of a person ill or dead from EVD, or through contaminated fomites. Symptoms appear suddenly approximately 2-21 days after infection and range from general flu-like symptoms to severe hemorrhagic symptoms. The average case fatality rate for EVD is approximately 50%. Due to the severity of symptoms and the lack of specific drugs, this virus is classified as a containment level 4 (BL4) pathogen. RABV is widely distributed throughout the world in bat and carnivorous hosts. Transmission occurs mainly through bites from infected animals. In humans and other mammals this virus causes encephalitis, although reservoir hosts appear not to exhibit the disease. People infected with RABV develop a severe disease characterized by neurological symptoms that has a 100% mortality rate. Nowadays, rabies vaccination is currently available and prophylactic treatments exist after possible exposure to the virus. However, for populations living in poor or developing countries, vaccination and anti-rabies prophylaxis are difficult to access. RABV is currently classified as a containment level 3 (BL3) pathogen. Thus, although EVD and rabies are preventable diseases, through prophylactic vaccines and antibody-based therapies, in many countries there is a large impact in terms of infections and deaths due to limited access to such therapies. Therefore, there is an urgent need to develop effective antivirals. However, selective drugs are not expected to appear on the market due to their limited commercial potential in low incoming countries affected by the EBOV and RABV. One possible strategy could be the development of broad-spectrum antiviral agents (BSAAs), which exert antiviral activity against several viruses. The development of BSAAs is a challenging task, however literature data indicate that some plant-derived natural products possess inhibitory effects on the replication of some DNA and RNA viruses, thus having the potential to be used for the development of BSAAs against emerging viruses. Several bioactive components, such as polyphenols, flavonoids, glucosides, terpenes and alkaloids, have been identified in specific plant extracts. Among these, for example, cranberry extract (CE) and epigallocatechin gallate (EGCG) have been shown to have antiviral activities against some viruses, such as influenza virus, hepatitis C virus and of Epstein-Barr, suggesting their potential use as broad-spectrum antivirals against the emerging or re-emerging viruses. With this research project, the Vesicular Stomatitis Virus (VSV) model pseudotyped with the glycoproteins of EBOV and RABV was used to investigate the antiviral activity of the CE and EGCG Results showed that CE inhibits EBOV and RABV infection and, in particular, the PAC-A2 component is the bio