HIV is a lentivirus (a subgroup of retrovirus) that causes the acquired immunodeficiency syndrome (AIDS). HIV infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells). However, HIV infection leads to a decrease in CD4+ T cell levels through multiple mechanisms. At this point, cell-mediated immune function declines. Envelope glycoprotein GP120 (or gp120) is a glycoprotein exposed on the surface of the HIV envelope. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. Since CD4 receptor binding is the most obvious step in HIV infection, gp120 is among the first targets of HIV vaccine research.

NBD-14270, a pyridine analogue, is a potent HIV-1 gp120 entry antagonist with an IC50 of 180 nM against 50 HIV-1 Env-pseudotyped viruses.

From: Didigu CA, Doms RW. Viruses. 2012 Feb;4(2):309-24.

In addition, NBD-14270 shows potent broad-spectrum antiviral activity and low cytotoxicity. NBD-14270 exhibits the best anti-HIV-1 activity and higher selectivity index value. Moreover, Francesca Curreli et al select a panel of 50 HIV-1 clinical isolates belonging to different subtypes, including primary, circulating, and early founder HIV-1 isolates, to assess the anti-HIV-1 activity of NBD-14270. Overall, NBD-14270 active against all clinical isolates tested, regardless of virus subtype (A-D). Furthermore, NBD-14270 is poorly active against the pseudovirus VSV-G, suggesting that the inhibitory activity of it is specific to HIV-1. Additionally, NBD-14270 does not induce toxicity in the U87-CD4-CXCR4 cell line at the doses used for this assay. Moreover, NBD-14270 can neutralize both infant and maternal HIV-1 variants. Importantly, NBD-14270 has inhibitory activity against a large panel of FDA-approved drug-resistant viruses, including Enfuvirtide-resistant viruses, and non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant viruses.

To sum up, NBD-14270 is a potent HIV-1 gp120 entry antagonist with broad-spectrum antiviral activity and low cytotoxicity.


[1] Francesca Curreli, et al. J Med Chem. 2020 Feb 27;63(4):1724-1749.