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Related Concept Videos

Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...

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Identification of Small Molecules as Zika Virus Entry Inhibitors.

Abhijeet Roy1, Hansam Cho1, Kristin V Lyles2

  • 1Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.

International Journal of Molecular Sciences
|November 13, 2025
PubMed
Summary

A new compound, Pyrimidine-Der1, effectively inhibits Zika virus (ZIKV) entry by targeting its envelope protein. This discovery offers a promising therapeutic strategy against ZIKV infections and associated health threats.

Keywords:
entry inhibitorsenvelope proteinflavivirusessmall molecule inhibitorsviral entryzika virus

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Area of Science:

  • Virology
  • Drug Discovery
  • Molecular Biology

Background:

  • Zika virus (ZIKV) poses significant public health risks, causing congenital abnormalities and neurological issues.
  • No approved therapeutics currently exist for ZIKV infection.
  • Targeting the ZIKV envelope (E) protein is a key antiviral strategy due to its role in viral entry.

Purpose of the Study:

  • To identify potential ZIKV entry inhibitors using molecular docking-based virtual screening.
  • To evaluate the efficacy of identified compounds against ZIKV infection.

Main Methods:

  • Molecular docking-based virtual screening of small-molecule libraries.
  • Microscale thermophoresis assay to confirm compound binding to ZIKV E protein.
  • Plaque inhibition assays with authentic ZIKV strains and time-of-addition assays.

Main Results:

  • Pyrimidine-Der1 was identified as a potent inhibitor of ZIKV infection.
  • Pyrimidine-Der1 demonstrated binding to the ZIKV E protein.
  • The compound showed effective inhibition of authentic ZIKV strains (IC50: ~3-5 μM) and blocked viral entry and fusion.

Conclusions:

  • Pyrimidine-Der1 is a promising candidate for ZIKV entry inhibition.
  • Further optimization and evaluation of Pyrimidine-Der1 are warranted for therapeutic development.