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

作者：Fei Yu, Xiaoqing Liu, Hailan Ou, Xinyu Li, Ruxin Liu, Xi Lv, Shiqi Xiao, Meilin Hu, Taizhen Liang, Tao Chen, Xuepeng Wei, Zhenglai Zhang, Sen Liu, Han Liu, Yiqiang Zhu, Guangyan Liu, Tianyong Tu, Pei-Wen Li, Hui Zhang, Ting Pan, Xiancai Ma · 发表于：mBio · 年份：2024 · DOI：10.1128/mbio.01088-24 · 被引用次数：11 · 研究领域：SARS-CoV-2 and COVID-19 Research、Immune Cell Function and Interaction、COVID-19 Clinical Research Studies

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent...