Discovery of a AHR pelargonidin agonist that counter-regulates Ace2 expression and attenuates ACE2-SARS-CoV-2 interaction

The severe acute respiratory syndrome (SARS)-CoV-2 is the pathogenetic agent of Corona Virus Induced Disease (COVID)19. The virus enters the human cells after binding to the angiotensin converting enzyme (ACE)2 receptor in target tissues. ACE2 expression is induced in response to inflammation. The colon expression of ACE2 is upregulated in patients with inflammatory bowel disease (IBD), highlighting a potential risk of intestinal inflammation in promoting viral entry in the human body. Because mechanisms that regulate ACE2 expression in the intestine are poorly understood and there is a need of anti-SARS-CoV-2 therapies, we have settled to investigate whether natural flavonoids might regulate the expression of Ace2 in intestinal models of inflammation. The results of these studies demonstrated that pelargonidin activates the Aryl hydrocarbon Receptor (AHR) in vitro and reverses intestinal inflammation caused by chronic exposure to high fat diet or to the intestinal braking-barrier agent TNBS in a AhR-dependent manner. In these two models, development of colon inflammation associated with upregulation of Ace2 mRNA expression. Colon levels of Ace2 mRNA were directly correlated with Tnf-α mRNA levels. Molecular docking studies suggested that pelargonidin binds a fatty acid binding pocket on the receptor binding domain of SARS-CoV-2 Spike protein. In vitro studies demonstrated that pelargonidin significantly reduces the binding of SARS-CoV-2 Spike protein to ACE2 and reduces the SARS-CoV-2 replication in a concentration-dependent manner. In summary, we have provided evidence that a natural flavonoid might hold potential in reducing intestinal inflammation and ACE2 induction in the inflamed colon in a AhR-dependent manner

Does cross-mating affect behavioral asymmetries and mating success of khapra beetle (Trogoderma granarium) strains?

Herein, sexual interactions and left-right asymmetries in brain and behavior (lateralization) of Czech and Turkish strains of Trogoderma granarium Everts (Coleoptera: Dermestidae) were investigated, assessing courtship and mating dynamics within each strain and in all possible cross mating combinations. Trogoderma granarium species identity was confirmed by DNA sequencing, using three mitochondrial DNA genes, Cytochrome Oxidase I (COI), large subunit ribosomal RNA (16S), and Cytochrome b (CYTb). The selected genetic markers were also used to examine any intraspecific variations between the two strains analyzed. The aligned COI and 16S DNA sequences obtained revealed several polymor- phisms, when both inter-and intra-strains analyzed. In behavioral experiments, more males of the Czech strain performed left-biased approaches (53%) than right-biased approaches (42%), with 20% of left-biased males and 13% of right-biased males using the right foreleg to explore females, achieving 18% and 10% successful copulations, respectively. Males of the Turkish strain exhibited right-(50%) or left-biased approaches (45%), with 17% of right-biased males and 21% of left biased males exploring females with the left foreleg, resulting in 15% and 20% mating success, respectively. During cross mating of strains, all possible combinations exhibited a population-level left-biased approach to the potential mates and a right-biased exploration of females with foreleg, leading to high successful copulations. Significant differences were noted in the duration of copulation of Turkish males interacting with females of the same strain (backside males 122.3 s, left biased males 72.0 s, and right-biased males 68.6 s). Overall, this research firstly sheds light on how cross-mating among strains can affect courtship, mating success and laterality in a key beetle pest

SARS-CoV2 infection impairs the metabolism and redox function of cellular glutathione

Viral infections sustain their replication cycle promoting a pro-oxidant environment in the host cell. In this context, specific alterations of the levels and homeostatic function of the tripeptide glutathione have been reported to play a causal role in the pro-oxidant and cytopathic effects (CPE) of the virus. In this study, these aspects were investigated for the first time in SARS-CoV2-infected Vero E6 cells, a reliable and well-characterized in vitro model of this infection. SARS-CoV2 markedly decreased the levels of cellular thiols, essentially lowering the reduced form of glutathione (GSH). Such an important defect occurred early in the CPE process (in the first 24 hpi). Thiol analysis in N-acetyl-Cys (NAC)-treated cells and membrane transporter expression data demonstrated that both a lowered uptake of the GSH biosynthesis precursor Cys and an increased efflux of cellular thiols, could play a role in this context. Increased levels of oxidized glutathione (GSSG) and protein glutathionylation were also observed along with upregulation of the ER stress marker PERK. The antiviral drugs Remdesivir (Rem) and Nelfinavir (Nel) influenced these changes at different levels, essentially confirming the importance or blocking viral replication to prevent GSH depletion in the host cell. Accordingly, Nel, the most potent antiviral in our in vitro study, produced a timely activation of Nrf2 transcription factor and a GSH enhancing response that synergized with NAC to restore GSH levels in the infected cells. Despite poor in vitro antiviral potency and GSH enhancing function, Rem treatment was found to prevent the SARS-CoV2-induced glutathionylation of cellular proteins. In conclusion, SARS-CoV2 infection impairs the metabolism of cellular glutathione. NAC and the antiviral Nel can prevent such defect in vitro

Cross-neutralization of SARS-CoV-2 B.1.1.7 and P.1 variants in vaccinated, convalescent and P.1 infected

Objectives: The emergence of new variants of concern (VOCs) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) around the world significantly complicated the exit from Coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to evaluate the serum neutralizing activity of three cohorts. Methods: BNT162b2-elicited serum (N = 103), candidates as hyper-immune plasma donors (N = 90) and patients infected with the SARS-CoV-2 P1 variant (N = 22) were enrolled. Three strains of SARS-CoV-2 have been tested: 20A.EU1, B.1.1.7 (alpha) and P.1 (gamma). Neutralizing antibodies (NT-Abs) titers against SARS-CoV-2 were evaluated. Results: B.1.1.7 and P.1 are less efficiently neutralized by convalescent wild-type infected serums if compared to 20A.EU1 strain (mean titer 1.6 and 6.7-fold lower respectively). BNT162b2 vaccine-elicited human sera show an equivalent neutralization potency on the B.1.1.7 but it is significantly lower for the P.1 variant (mean titer 3.3-fold lower). Convalescent P.1 patients are less protected from other SARS-CoV-2 strains with an important reduction of neutralizing antibodies against 20A.EU1 and B.1.1.7, about 12.2 and 10.9-fold, respectively. Conclusions: BNT162b2 vaccine confers immunity against all the tested VOCs, while previous SARS-CoV-2 infection may be less protective

Essential oils from three Cupressaceae species as stored wheat protectants: will they kill different developmental stages of nine noxious arthropods?

Several plant species belonging to the Cupressaceae family are used in the industry for the production of various pharmaceuticals, food additives, and paint materials. Various essential oils (EOs) derived from these species have been examined for their insecticidal and acaricidal actions. In this study, we examined the efficacy of Hesperocyparis arizonica, × Hesperotropsis leylandii, and Juniperus × pfitzeriana EOs as wheat protectants to control different stages of development of nine stored-product pest species (1 dermestid, 1 curculionid, 1 bostrychid, 1 silvanid, 1 mite, and 4 tenebrionids). The EOs of the above plants were characterized by high percentages of monoterpenoids among which α-pinene (16.7–41.0%), sabinene (5.4–10.4%), δ-3-carene (20.5%), limonene (6.9–15.4%), bornyl acetate (36.3%), and trans-sabinyl acetate (18.2%) were the most representative ones depending on the species. Mortality caused by the three EOs at 1000 ppm to Trogoderma granarium adults ranged between 88.9 and 100.0%, after 7 days (d). The EO of H. arizonica, at the highest concentration (1000 ppm), killed 94.4% of exposed Oryzaephilus surinamensis adults, after one week. Complete mortality (100%) of Alphitobius diaperinus larvae occurred after exposure for 5 d to × H. leylandii EO at 1000 ppm. High mortality rates were also reported for Tribolium castaneum (93.3%) and Tribolium confusum (91.1%) larvae, and Tenebrio molitor adults (87.9%) at 1000 ppm of × H. leylandii EO, 7 d after exposure. This investigation shows that × H. leylandii EO provided elevated mortality levels to the majority of the tested pests exhibiting high potential to be considered as an effective grain protectant