Kaempferol inhibits Pseudorabies virus replication in vitro through regulation of MAPKs and NF-κB signaling pathways

et al. 2022

FEBS Open Bio

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been spreading globally for over 2 years, causing serious contagious disease and incalculable damage. The introduction of vaccines has slowed the spread of SARS‐CoV‐2 to some extent, but there remains a need for specific and effective treatment. The high chemical diversity and safety profiles of natural products make them a potential source of effective anti‐SARS‐CoV‐2 drugs. Cotton plant is one of the most important economic and medical crops and is the source of a large number of antiviral phytochemicals. In this work, we used SARS‐CoV‐2 main protein (M pro ) as the target to identify potential anti‐SARS‐CoV‐2 natural products in cotton. An in vitro assay showed that of all cotton tissues examined, cotton flower extracts (CFs) exhibited optimal inhibitory effects against M pro . We proceeded to use the CF metabolite database to screen natural M pro inhibitors by combining virtual screening and biochemical assays. We identified that several CF natural products, including astragalin, myricitrin, and astilbin, significantly inhibited M pro with half‐maximal inhibitory concentrations (IC50s) of 0.13, 10.73, and 7.92 μ m , respectively. These findings may serve as a basis for further studies into the suitability of cotton as a source of potential therapeutics for SARS‐CoV‐2.

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Cotton flower metabolites inhibit SARS‐CoV‐2 main protease

et al. 2022

FEBS Open Bio

“…The virus was proliferated in PK-15 cells. The 50% tissue culture infectious dose (TCID 50 ) was determined to be 10 −7.1 mL −1 [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

Dihydromyricetin Inhibits Pseudorabies Virus Multiplication In Vitro by Regulating NF-κB Signaling Pathway and Apoptosis

Zhao

Chen

et al. 2023

Veterinary Sciences

Self Cite

Pseudorabies virus (PRV) infections have caused huge economic losses to the breeding industry worldwide, especially pig husbandry. PRV could threaten human health as an easily ignored zoonotic pathogen. The emergence of new mutants significantly reduced the protective effect of vaccination, indicating an urgent need to develop specific therapeutic drugs for PRV infection. In this study, we found that dihydromyricetin (DMY) could dose-dependently restrain PRV infection in vitro with an IC50 of 161.34 μM; the inhibition rate of DMY at a concentration of 500 μM was 92.16 %. Moreover, the mode of action showed that DMY directly inactivated PRV virion and inhibited viral adsorption and cellular replication. DMY treatment could improve PRV-induced abnormal changes of the NF-κB signaling pathway and excessive inflammatory response through regulation of the contents of IκBα and p-P65/P65 and the transcriptional levels of cytokines (TNF-α, IL-1β and IL-6). Furthermore, DMY promoted the apoptosis of PRV-infected cells through the regulation of the expressions of Bax and Bcl-xl and the transcriptional levels of Caspase-3, Bax, Bcl-2 and Bcl-xl, thereby limiting the production of progeny virus. These findings indicated that DMY could be a candidate drug for the treatment of PRV infection.

“…In order to elucidate which stage of viral infection was inhibited by myricetin, the mode of action assay was performed by the following five tests ( Chen et al, 2021 ). (1) Pretreatment: cells were incubated with myricetin (500 μM) for 1 h at 37°C prior to PRV infection (100 TCID 50 ).…”

Section: Methodsmentioning

confidence: 99%

Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense

et al. 2022

Front. Microbiol.

Self Cite

Myricetin, a polyhydroxyflavone compound, is one of the main ingredients of various human foods and therefore also known as dietary flavonoids. Due to the continuous emergence of resistant strains of herpesviruses, novel control measures are required. In the present study, myricetin exhibited potent antiviral activity against pseudorabies virus (PRV), a model organism of herpesvirus. The suppression rate could reach up to 96.4% at a concentration of 500 μM in cells, and the 50% inhibitory concentration (IC 50 ) was 42.69 μM. Moreover, the inhibitory activity was not attenuated by the increased amount of infective dose, and a significant reduction of intracellular PRV virions was observed by indirect immunofluorescence. A mode of action study indicated that myricetin could directly inactivate the virus in vitro, leading to inhibition of viral adsorption, penetration and replication in cells. In addition to direct killing effect, myricetin could also activate host antiviral defense through regulation of apoptosis-related gene expressions (Bcl-2, Bcl-xl, Bax), NF-κB and MAPK signaling pathways and cytokine gene expressions (IL-1α, IL-1β, IL-6, c-Jun, STAT1, c-Fos, and c-Myc). In PRV-infected mouse model, myricetin could enhance the survival rate by 40% at 5 days post infection, and viral loads in kidney, liver, lung, spleen, and brain were significantly decreased. The pathological changes caused by PRV infection were improved by myricetin treatment. The gene expressions of inflammatory factors (MCP-1, G-CSF, IL-1α, IL-1β, and IL-6) and apoptotic factors (Bcl-xl, Bcl-2, and Bax) were regulated by myricetin in PRV-infected mice. The present findings suggest that myricetin can effectively inhibit PRV infection and become a candidate for development of new anti-herpesvirus drugs.