In RNA viruses, a small increase in their mutation rates can be sufficient to exceed their threshold of viability. Lethal mutagenesis is a therapeutic strategy based on the use of mutagens, driving viral populations to extinction. Extinction catastrophe can be experimentally induced by promutagenic nucleosides in cell culture models. The loss of HIV infectivity has been observed after passage in 5-hydroxydeoxycytidine or 5,6-dihydro-5-aza-2′-deoxycytidine while producing a two-fold increase in the viral mutation frequency. Among approved nucleoside analogs, experiments with polioviruses and other RNA viruses suggested that ribavirin can be mutagenic, although its mechanism of action is not clear. Favipiravir and molnupiravir exert an antiviral effect through lethal mutagenesis. Both drugs are broad-spectrum antiviral agents active against RNA viruses. Favipiravir incorporates into viral RNA, affecting the G→A and C→U transition rates. Molnupiravir (a prodrug of β-d-N⁴-hydroxycytidine) has been recently approved for the treatment of SARS-CoV-2 infection. Its triphosphate derivative can be incorporated into viral RNA and extended by the coronavirus RNA polymerase. Incorrect base pairing and inefficient extension by the polymerase promote mutagenesis by increasing the G→A and C→U transition frequencies. Despite having remarkable antiviral action and resilience to drug resistance, carcinogenic risks and genotoxicity are important concerns limiting their extended use in antiviral therapy.

The goal of this work was to investigate the impact of the flavoring of some aromatic plants/spices, including rosemary (R), lemon (L) and orange (O) at the concentration of 5% and 35% (w/w) added by 2 methods (conventional maceration and direct flavoring), on quality attributes, chemical changes and oxidative stability of extra virgin olive oil (EVOO). Six flavored oils were obtained (EVOO + O, O + O, EVOO + R, O + R, EVOO + L and O + L). The physicochemical parameters (water content, refractive index, acidity and peroxide value, extinction coefficient, fatty acids, volatile aroma profiles, Rancimat test, phenols and pigments composition) of the flavored oils were investigated. Based on the results obtained, it was observed that flavoring with a conventional process provided increased oxidative stability to the flavored oils, especially with rosemary (19.38 ± 0.26 h), compared to that of unflavored oil. The volatile profiles of the different flavored oils revealed the presence of 34 compounds with the dominance of Limonene. The fatty acid composition showed an abundance of mono-unsaturated fatty acids followed by poly-unsaturated ones. Moreover, a high antioxidant activity, a significant peripheral analgesic effect (77.7% of writhing inhibition) and an interesting gastroprotective action (96.59% of ulcer inhibition) have been observed for the rosemary-flavored oil. Indeed, the flavored olive oils of this study could be used as new functional foods, leading to new customers and further markets.

Several epidemiological studies demonstrated that coxsackievirus B4 (CVB4) causes viral pancreatitis and can ultimately result in type 1 diabetes mellitus (T1D). Prevention of CVB4 infection is therefore highly desirable. There is currently no vaccine or antiviral therapeutic reagent in clinical use. VLP are structurally similar to native virus particles and therefore are far better immunogens than any other subunit vaccines. Many studies have shown the potential of capsid protein VP1 on providing protective effects from different viral strains. In this study, we contributed towards the development of a CVB4 VLP-based vaccine from the total protein VP1 of the diabetogenic CVB4E2 strain and assessed whether it could induce a protective immunity against both the wild-type CVB4JBV and the diabetogenic CVB4E2 strains in mice model. Serum samples, taken from mice immunized with VLP, were assayed in vitro for their anti-CVB4 neutralizing activity and in vivo for protective activity. We show that VLP vaccine generates robust immune responses that protect mice from lethal challenges. Results demonstrate that CVB4 VP1 capsid proteins expressed in insect cells have the intrinsic capacity to assemble into non-infectious VLP, which afforded protection from CVB4 infection to mice when used as a vaccine.