Dataset Information

Piceatannol as an Antiviral Inhibitor of PRV Infection In Vitro and In Vivo.

ABSTRACT: Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiviral activity of piceatannol. The results showed that piceatannol could restrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC₅₀) was 0.0307 mg/mL, and the selectivity index (SI, CC₅₀/IC₅₀) was 3.68. Piceatannol could exert an anti-PRV effect by reducing the transcription level of viral genes, inhibiting PRV-induced apoptosis and elevating the levels of IL-4, TNF-α and IFN-γ in the serum of mice. Animal experiments showed that piceatannol could delay the onset of disease, reduce the viral load in the brain and kidney and reduce the pathological changes in the tissues and organs of the mice to improve the survival rate of the mice (14.3%). Therefore, the anti-PRV activity of piceatannol in vivo and in vitro was systematically evaluated in this study to provide scientific data for developing a new alternative measure for controlling PRV infection.

SUBMITTER: Wang Z

PROVIDER: S-EPMC10375968 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Piceatannol as an Antiviral Inhibitor of PRV Infection In Vitro and In Vivo.

Wang Zhiying Z Cai Xiaojing X Ren Zhiyuan Z Shao Yi Y Xu Yongkang Y Fu Lian L Zhu Yan Y

Animals : an open access journal from MDPI 20230721 14

Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiviral activity of piceatannol. The results showed that piceatannol could restrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 0.0307 mg/mL, and the selectivity index (SI, CC50/IC50) was 3.68. Piceatannol could ...[more]

PMID: 37508153

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Project description:Peptides derived from the C-terminal heptad repeat (CHR) region of the human immunodeficiency virus type 1 (HIV-1) fusogenic protein gp41 are potent viral entry inhibitors, and currently, enfuvirtide (T-20) is the only one approved for clinical use; however, emerging drug resistance largely limits its efficacy. In this study, we generated a novel lipopeptide inhibitor, named LP-19, by integrating multiple design strategies, including an N-terminal M-T hook structure, an HIV-2 sequence, intrahelical salt bridges, and a membrane-anchoring lipid tail. LP-19 showed stable binding affinity and highly potent, broad, and long-lasting antiviral activity. In in vitro studies, LP-19 efficiently inhibited HIV-1-, HIV-2-, and simian immunodeficiency virus (SIV)-mediated cell fusion, viral entry, and infection, and it was highly active against diverse subtypes of primary HIV-1 isolates and inhibitor-resistant mutants. Ex vivo studies demonstrated that LP-19 exhibited dramatically increased anti-HIV activity and an extended half-life in rhesus macaques. In short-term monotherapy, LP-19 reduced viral loads to undetectable levels in acutely and chronically simian-human immunodeficiency virus (SHIV)-infected monkeys. Therefore, this study offers an ideal HIV-1/2 fusion inhibitor for clinical development and emphasizes the importance of the viral fusion step as a drug target.IMPORTANCE The peptide drug T-20 is the only viral fusion inhibitor in the clinic, which is used for combination therapy of HIV-1 infection; however, it requires a high dosage and easily induces drug resistance, calling for a new drug with significantly improved pharmaceutical profiles. Here, we have developed a short-lipopeptide-based fusion inhibitor, termed LP-19, which mainly targets the conserved gp41 pocket site and shows highly potent inhibitory activity against HIV-1, HIV-2, and even SIV isolates. LP-19 exhibits dramatically increased antiviral activity and an extended half-life in rhesus macaques, and it has potent therapeutic efficacy in SHIV-infected monkeys, highlighting its high potential as a new viral fusion inhibitor for clinical use.

Dataset Information

Piceatannol as an Antiviral Inhibitor of PRV Infection In Vitro and In Vivo.

Publications

Piceatannol as an Antiviral Inhibitor of PRV Infection In Vitro and In Vivo.

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