A Class of Potent Inhibitors of the HIV-1 Nucleocapsid Protein Based on Aminopyrrolic Scaffolds

Stefano Ciaco, Nicolas Humbert, Eléonore Real, Christian Boudier, Oscar Francesconi, Stefano Roelens, Cristina Nativi, Carole Seguin-Devaux, Mattia Mori, Yves Mély*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)


The HIV-1 nucleocapsid protein 7 (NC) is a potential target for effective antiretroviral therapy due to its central role in virus replication, mainly linked to nucleic acid (NA) chaperone activity, and low susceptibility to drug resistance. By screening a compounds library, we identified the aminopyrrolic compound CN14_17, a known carbohydrate binding agent, that inhibits the NC chaperone activity in the low micromolar range. Different from most of available NC inhibitors, CN14_17 fully prevents the NC-induced annealing of complementary NA sequences. Using fluorescence assays and isothermal titration calorimetry, we found that CN14_17 competes with NC for the binding to NAs, preferentially targeting single-stranded sequences. Molecular dynamics simulations confirmed that binding to cTAR occurs preferably within the guanosine-rich single stranded sequence. Finally, CN14_17 exhibited antiretroviral activity in the low micromolar range, although with a moderate therapeutic index. Overall, CN14_17 might be the progenitor of a new promising class of NC inhibitors.

Original languageEnglish
Pages (from-to)698-705
Number of pages8
JournalACS Medicinal Chemistry Letters
Issue number5
Publication statusPublished - 14 May 2020


  • antiviral
  • fluorescence
  • HIV-1
  • inhibitor
  • NCp7
  • nucleocapsid protein


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