A dual character of flavonoids in influenza A virus replication and spread through modulating cell-autonomous immunity by MAPK signaling pathways

Abstract

Flavonoids are well known as a large class of polyphenolic compounds, which have a variety of physiological activities, including anti-influenza virus activity. The influenza A/WSN/33 infected A549 cells have been used to screen anti-influenza virus drugs from natural flavonoid compounds library. Unexpectedly, some flavonoid compounds significantly inhibited virus replication, while the others dramatically promoted virus replication. In this study, we attempted to understand these differences between flavonoid compounds in their antivirus mechanisms. Hesperidin and kaempferol were chosen as representatives of both sides, each of which exhibited the opposite effects on influenza virus replication. Our investigation revealed that the opposite effects produced by hesperidin and kaempferol on influenza virus were due to inducing the opposite cell-autonomous immune responses by selectively modulating MAP kinase pathways: hesperidin up-regulated P38 and JNK expression and activation, thus resulting in the enhanced cell-autonomous immunity; while kaempferol dramatically down-regulated p38 and JNK expression and activation, thereby suppressing cell-autonomous immunity. In addition, hesperidin restricted RNPs export from nucleus by down-regulating ERK activation, but kaempferol promoted RNPs export by up-regulating ERK activation. Our findings demonstrate that a new generation of anti-influenza virus drugs could be developed based on selective modulation of MAP kinase pathways to stimulate cell-autonomous immunity.

Identification of Potent COVID-19 Main Protease (Mpro) Inhibitors from Natural Polyphenols: An in Silico Strategy Unveils a Hope against CORONA

“…Previous reports also suggest anti-influenza virus potential of hesperidin and apiin (31,32), the anti-DENV activity of rutin (33) while the anti-rotavirus potential of diosmin (34) which further affirm the potential of these compounds against COVID-19. Hesperidin and diosmin are flavanone glycoside which is richly found in the citrus including lemons, grapefruits and sweet oranges (35,36).…”

Antiviral, Cytotoxic and Antioxidant Effects of Tanacetum Vulgare L. Crude Extract In Vitro

“…(K -A) / (K -UA), where: K -control absorption (K 1 -K 0 ) A -sample absorption (A 1 -A 0 ) UA -absorption of uric acid solution (UA 1 -UA 0 ) C UA -uric acid concentration (mmol/l) expression (modulation of MAP-kinase pathway) resulting in enhanced cell-immunity, by restriction of RNPs export from the nucleus (hesperidin). 31,32 Studies performed with polyphenolic extract from popular Bulgarian medicinal plant Geranium sanguineum revealed strong anti-herpes, anti-influenza (virucidal effect including) and antioxidant effects in model systems, cell cultures and in mice. [33][34][35][36] The registered antioxidant effect of T. vulgare could be due to the presence of polyphenolic compounds such as 3,5-O-dicaffeoylquinic acid (3,5-DCQA), axillarin and luteolin and vitamin C. 37 Phenolic compounds have been reported to have multiple biological effects, including antioxidant activity by scavenging reactive oxygen, nitrogen, and chlorine species, such as superoxide anion, hydroxyl radical, peroxyl radicals, hypochlorous acid and peroxynitrous acid.…”

Hydrodynamic Cavitation-based Rapid Expansion of Hesperidin-rich Products from Waste Citrus Peel as a Potential Tool Against COVID-19

“…In murine experiments, hesperidin, at the dose of 100 mg per kg of body weight and with intragastric administration, was found to effectively inhibit influenza A virus replication and spread, by up-regulating certain cell-autonomous immune responses [25]. It is worth noting that, quite surprisingly, other flavonoids, such as kaempferol, induced down-regulation and promoted virus replication.…”