Wikstroelide M potently inhibits HIV replication by targeting reverse transcriptase and integrase nuclear...

Area of Science:

• Natural Product Chemistry
• Virology
• Medicinal Chemistry

Background:

• Human Immunodeficiency Virus (HIV) remains a significant global health challenge.
• Daphne acutiloba Rehder is a traditional medicinal plant with potential therapeutic compounds.
• Daphnane diterpenes represent a class of natural products with diverse biological activities.

Purpose of the Study:

• To investigate the anti-HIV activity of wikstroelide M, a daphnane diterpene isolated from Daphne acutiloba.
• To elucidate the mechanism of action of wikstroelide M against HIV infection.

Main Methods:

• Cytopathic effect and p24 quantification assays were used to evaluate anti-HIV activity against various HIV strains.
• Real-time PCR and ELISA were employed to analyze the inhibition of HIV reverse transcription.
• Cell-based imaging and molecular docking were utilized to study HIV-1 integrase nuclear translocation and LEDGF/p75-IN interaction.

Main Results:

• Wikstroelide M exhibited potent inhibition against multiple HIV-1 and HIV-2 strains, with EC50 values in the ng·mL⁻¹ range.
• The compound effectively inhibited HIV-1IIIB induced cytolysis in MT-4 cells.
• Mechanistic studies revealed that wikstroelide M targets HIV-1 reverse transcriptase and integrase nuclear translocation by disrupting the LEDGF/p75-integrase interaction.

Conclusions:

• Wikstroelide M is a promising inhibitor of both HIV-1 and HIV-2.
• The anti-HIV mechanisms include the inhibition of reverse transcriptase activity and integrase nuclear translocation.
• Disruption of the LEDGF/p75-integrase interaction is a key aspect of wikstroelide M's antiviral action.