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  11. The Histamine Receptor H1 Acts As An Alternative Receptor For Sars-cov-2.

The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2.

Fei Yu1, Xiaoqing Liu2,3, Hailan Ou1

  • 1Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.

Mbio
|July 2, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Histamine receptor H1 (HRH1) acts as an alternative SARS-CoV-2 receptor, enhancing ACE2-dependent entry. Antihistamine drugs targeting HRH1 block viral infection, showing therapeutic potential for COVID-19.

Area of Science:

  • Virology
  • Immunology
  • Pharmacology

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes host factors like human angiotensin-converting enzyme 2 (hACE2) for entry.
  • Antihistamine drugs, specifically histamine receptor H1 (HRH1) antagonists, have shown potent inhibition of SARS-CoV-2 infection.

Purpose of the Study:

  • To investigate the role of HRH1 as a SARS-CoV-2 receptor.
  • To elucidate the mechanism by which HRH1 facilitates viral entry.
  • To evaluate the therapeutic potential of HRH1 antagonists against SARS-CoV-2.

Main Methods:

  • Direct binding assays between HRH1 and the SARS-CoV-2 spike protein.
  • Co-immunoprecipitation to assess HRH1 interaction with hACE2.
  • Inhibition assays using various SARS-CoV-2 mutants and antihistamine drugs.
Keywords:
HRH1SARS-CoV-2antihistaminereceptor

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  • Authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments.

    • Main Results:

    • HRH1 directly binds to the SARS-CoV-2 spike protein, acting as an alternative receptor.
    • HRH1 synergistically enhances hACE2-dependent viral entry through interaction with hACE2.
    • Antihistamine drugs effectively inhibit SARS-CoV-2 infection by blocking the spike protein-HRH1 interaction, with an average IC50 of 2.4 µM against various mutants.
    • Prophylactic effects were confirmed in vivo, demonstrating therapeutic potential.

    Conclusions:

    • HRH1 serves as an alternative receptor for SARS-CoV-2 and enhances hACE2-mediated entry.
    • Antihistamine drugs targeting HRH1 represent a viable therapeutic strategy for combating coronavirus disease 19 (COVID-19).
    • Repurposing antihistamines offers a promising avenue for COVID-19 treatment.
    spike
    viral entry