Recent Progress in the Development of HIV-1 Entry Inhibitors: From Small Molecules to Potent Anti-HIV Agents

Suttisintong, Khomson; Kaewchangwat, Narongpol; Thanayupong, Eknarin; Nerungsi, Chakkrapan; Srikun, Onsiri; Pungpo, Pornpan

doi:10.2174/1568026619666190712204050

Cited by 7 publications

(2 citation statements)

References 169 publications

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“…The receptor‐binding domain (RBD) of the spike protein (S) interacts with the protease domain of the angiotensin‐converting enzyme 2 (ACE2). Interference with the interactions between these proteins might provide a path to the development of antivirals that would prevent cell fusion and entry, as has been shown in the case of HIV through the development of peptidic and small‐molecule fusion inhibitors [36]. For that reason, accurate description of the interaction between the RBD and ACE2 is very important.…”

Section: Resultsmentioning

confidence: 99%

Ligand‐centered assessment of SARS‐CoV‐2 drug target models in the Protein Data Bank

et al. 2020

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A bright spot in the SARS‐CoV‐2 (CoV‐2) coronavirus pandemic has been the immediate mobilization of the biomedical community, working to develop treatments and vaccines for COVID‐19. Rational drug design against emerging threats depends on well‐established methodology, mainly utilizing X‐ray crystallography, to provide accurate structure models of the macromolecular drug targets and of their complexes with candidates for drug development. In the current crisis, the structural biological community has responded by presenting structure models of CoV‐2 proteins and depositing them in the Protein Data Bank (PDB), usually without time embargo and before publication. Since the structures from the first‐line research are produced in an accelerated mode, there is an elevated chance of mistakes and errors, with the ultimate risk of hindering, rather than speeding up, drug development. In the present work, we have used model‐validation metrics and examined the electron density maps for the deposited models of CoV‐2 proteins and a sample of related proteins available in the PDB as of April 1, 2020. We present these results with the aim of helping the biomedical community establish a better‐validated pool of data. The proteins are divided into groups according to their structure and function. In most cases, no major corrections were necessary. However, in several cases significant revisions in the functionally sensitive area of protein–inhibitor complexes or for bound ions justified correction, re‐refinement, and eventually reversioning in the PDB. The re‐refined coordinate files and a tool for facilitating model comparisons are available at https://covid-19.bioreproducibility.org. Database Validated models of CoV‐2 proteins are available in a dedicated, publicly accessible web service https://covid-19.bioreproducibility.org

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Section: Resultsmentioning

confidence: 99%

Ligand‐centered assessment of SARS‐CoV‐2 drug target models in the Protein Data Bank

et al. 2020

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“…CD4-mimetic compounds (CD4mc) can potentially contribute to the control of the HIV-1 pandemic. Work from our group and others demonstrated that compounds that mimic the T-cell receptor CD4 and its interaction with the HIV-1 viral envelope glycoprotein trimer (Env) are able to inhibit viral entry into host cells by competitive inhibition and by premature allosteric activation of the HIV Env. Such premature activation leads to a series of conformational changes in Env that result in deactivation of the virus .…”

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confidence: 99%

Identification of gp120 Residue His105 as a Novel Target for HIV-1 Neutralization by Small-Molecule CD4-Mimics

Fritschi

Liang

Mohammadi

et al. 2021

ACS Med. Chem. Lett.

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The design and synthesis of butyl chain derivatives at the indane ring 3-position of our lead CD4-mimetic compound BNM-III-170 that inhibits human immunodeficiency virus (HIV-1) infection are reported. Optimization efforts were guided by crystallographic and computational analysis of the small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120. Biological evaluation of 11−21 revealed that members of this series of CD4-mimetic compounds are able to inhibit HIV-1 viral entry into target cells more potently and with greater breadth compared to BNM-III-170. Crystallographic analysis of the binding pocket of 14, 16, and 17 revealed a novel hydrogen bonding interaction between His105 and a primary hydroxyl group on the butyl side chain. Further optimization of this interaction with the His105 residue holds the promise of more potent CD4-mimetic compounds.

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Quinolines and isoquinolines as HIV-1 inhibitors: Chemical structures, action targets, and biological activities

Chen

Cao

et al. 2023

Bioorganic Chemistry

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Recent Progress in the Development of HIV-1 Entry Inhibitors: From Small Molecules to Potent Anti-HIV Agents

Cited by 7 publications

References 169 publications

Ligand‐centered assessment of SARS‐CoV‐2 drug target models in the Protein Data Bank

Ligand‐centered assessment of SARS‐CoV‐2 drug target models in the Protein Data Bank

Identification of gp120 Residue His105 as a Novel Target for HIV-1 Neutralization by Small-Molecule CD4-Mimics

Quinolines and isoquinolines as HIV-1 inhibitors: Chemical structures, action targets, and biological activities

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