Inhibition of NF-κB-dependent HIV-1 replication by the marine natural product bengamide A

Antiviral Research
Ian TietjenMark A Brockman

Abstract

HIV-1 inhibitors that act by mechanisms distinct from existing antiretrovirals can provide novel insights into viral replication and potentially inform development of new therapeutics. Using a multi-cycle HIV-1 replication assay, we screened 252 pure compounds derived from marine invertebrates and microorganisms and identified 6 (actinomycin Z2, bastadin 6, bengamide A, haliclonacyclamine A + B, keramamine C, neopetrosiamide B) that inhibited HIV-1 with 50% effective concentrations (EC50s) of 3.8 μM or less. The most potent inhibitor, bengamide A, blocked HIV-1 in a T cell line with an EC50 of 0.015 μM and in peripheral blood mononuclear cells with an EC50 of 0.032 μM. Bengamide A was previously described to inhibit NF-κB signaling. Consistent with this mechanism, bengamide A suppressed reporter expression from an NF-κB-driven minimal promoter and an HIV-1 long terminal repeat (LTR) with conserved NF-κB response elements, but lacked activity against an LTR construct with mutation of these elements. In single-cycle HIV-1 infection assays, bengamide A also suppressed viral protein expression when viruses encoded an intact LTR but exhibited minimal activity against those with mutated NF-κB elements. Finally, bengamide A did not in...Continue Reading

Citations

Sep 29, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Karlo WittineSandra Kraljević Pavelić
Jul 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maggie C DuncanIan Tietjen
Jul 11, 2020·Biomolecules·Gennaro RiccioChiara Lauritano

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.