Dataset Information

Structure-Based Identification of Natural-Product-Derived Compounds with Potential to Inhibit HIV-1 Entry.

ABSTRACT: Broadly neutralizing antibodies (bNAbs) are potent in neutralizing a wide range of HIV strains. VRC01 is a CD4-binding-site (CD4-bs) class of bNAbs that binds to the conserved CD4-binding region of HIV-1 envelope (env) protein. Natural products that mimic VRC01 bNAbs by interacting with the conserved CD4-binding regions may serve as a new generation of HIV-1 entry inhibitors by being broadly reactive and potently neutralizing. This study aimed to identify compounds that mimic VRC01 by interacting with the CD4-bs of HIV-1 gp120 and thereby inhibiting viral entry into target cells. Libraries of purchasable natural products were virtually screened against clade A/E recombinant 93TH057 (PDB: 3NGB) and clade B (PDB ID: 3J70) HIV-1 env protein. Protein-ligand interaction profiling from molecular docking and dynamics simulations showed that the compounds had intermolecular hydrogen and hydrophobic interactions with conserved amino acid residues on the CD4-binding site of recombinant clade A/E and clade B HIV-1 gp120. Four potential lead compounds, NP-005114, NP-008297, NP-007422, and NP-007382, were used for cell-based antiviral infectivity inhibition assay using clade B (HXB2) env pseudotype virus (PV). The four compounds inhibited the entry of HIV HXB2 pseudotype viruses into target cells at 50% inhibitory concentrations (IC₅₀) of 15.2 µM (9.7 µg/mL), 10.1 µM (7.5 µg/mL), 16.2 µM (12.7 µg/mL), and 21.6 µM (12.9 µg/mL), respectively. The interaction of these compounds with critical residues of the CD4-binding site of more than one clade of HIV gp120 and inhibition of HIV-1 entry into the target cell demonstrate the possibility of a new class of HIV entry inhibitors.

SUBMITTER: Ugwu-Korie N

PROVIDER: S-EPMC9865492 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Structure-Based Identification of Natural-Product-Derived Compounds with Potential to Inhibit HIV-1 Entry.

Ugwu-Korie Nneka N Quaye Osbourne O Wright Edward E Languon Sylvester S Agyapong Odame O Broni Emmanuel E Gupta Yash Y Kempaiah Prakasha P Kwofie Samuel K SK

Molecules (Basel, Switzerland) 20230104 2

Broadly neutralizing antibodies (bNAbs) are potent in neutralizing a wide range of HIV strains. VRC01 is a CD4-binding-site (CD4-bs) class of bNAbs that binds to the conserved CD4-binding region of HIV-1 envelope (env) protein. Natural products that mimic VRC01 bNAbs by interacting with the conserved CD4-binding regions may serve as a new generation of HIV-1 entry inhibitors by being broadly reactive and potently neutralizing. This study aimed to identify compounds that mimic VRC01 by interactin ...[more]

PMID: 36677538

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Dataset Information

Structure-Based Identification of Natural-Product-Derived Compounds with Potential to Inhibit HIV-1 Entry.

Publications

Structure-Based Identification of Natural-Product-Derived Compounds with Potential to Inhibit HIV-1 Entry.

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