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Guava flavonoid glycosides prevent influenza A virus infection via rescue of P53 activity.
Khalil H1, Abd El Maksoud AI2, Roshdey T1, El-Masrey S1.
Author information
Abstract
Influenza is a highly infectious disease caused by three types of viruses including influenza A virus (IAV), influenza B virus and rarely influenza C virus. IAV is a major, global public health threat, causing approximately 500,000 deaths per year worldwide. The new strains of IAV are emerged due to mutation called antigenic shift that results in a new subtypes of the virus that show resistance to common antiviral drugs. Here, Guava and Lemon extracts including the green leaves and flowers, were investigated for their activity against IAV replication in human A549 cells. Concomitantly, cytotoxicity of potent extract on host cell multiplication was assessed. Our results reveal that Guava extracts inhibit IAV replication indicated by viral nucleoprotein (NP) expression profile and traditional plaque assay. Interestingly, treatment with Guava extract inactivates Akt protein kinase and stimulates the pro-apoptotic protein P53 at earlier stage of infection. Furthermore, the purified Guava flavonoid glycosides (GFGs) showed competitive inhibition of IAV virus replication via early regulation of IL-1β and IL-8 in association with P53 gene expression. The docking analysis between GFGs and protein structure of upstream targets for Akt signaling pathway indicates a sufficient interaction and stabilization with Gbr2 protein. These data indicate that treatment with GFGs disturbs IAV replication via activation of P53 and its apoptotic related factors following infection. Collectively, targeting of essential host kinases that are involved in the replication cycle of IAV and rescue of P53 activity by GFGs could represent a new strategy to eradicate IAV. This article is protected by copyright. All rights reserved.
KEYWORDS:
Guava flavonoid glycosides; Influenza A virus; P53 rescue; drug discovery
PMID: 30153335 DOI: 10.1002/jmv.25295
Khalil H1, Abd El Maksoud AI2, Roshdey T1, El-Masrey S1.
Author information
Abstract
Influenza is a highly infectious disease caused by three types of viruses including influenza A virus (IAV), influenza B virus and rarely influenza C virus. IAV is a major, global public health threat, causing approximately 500,000 deaths per year worldwide. The new strains of IAV are emerged due to mutation called antigenic shift that results in a new subtypes of the virus that show resistance to common antiviral drugs. Here, Guava and Lemon extracts including the green leaves and flowers, were investigated for their activity against IAV replication in human A549 cells. Concomitantly, cytotoxicity of potent extract on host cell multiplication was assessed. Our results reveal that Guava extracts inhibit IAV replication indicated by viral nucleoprotein (NP) expression profile and traditional plaque assay. Interestingly, treatment with Guava extract inactivates Akt protein kinase and stimulates the pro-apoptotic protein P53 at earlier stage of infection. Furthermore, the purified Guava flavonoid glycosides (GFGs) showed competitive inhibition of IAV virus replication via early regulation of IL-1β and IL-8 in association with P53 gene expression. The docking analysis between GFGs and protein structure of upstream targets for Akt signaling pathway indicates a sufficient interaction and stabilization with Gbr2 protein. These data indicate that treatment with GFGs disturbs IAV replication via activation of P53 and its apoptotic related factors following infection. Collectively, targeting of essential host kinases that are involved in the replication cycle of IAV and rescue of P53 activity by GFGs could represent a new strategy to eradicate IAV. This article is protected by copyright. All rights reserved.
KEYWORDS:
Guava flavonoid glycosides; Influenza A virus; P53 rescue; drug discovery
PMID: 30153335 DOI: 10.1002/jmv.25295