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. 2021 Aug:560:110-115.
doi: 10.1016/j.virol.2021.05.009. Epub 2021 May 25.

Azelastine inhibits viropexis of SARS-CoV-2 spike pseudovirus by binding to SARS-CoV-2 entry receptor ACE2

Shuai Ge  1 , Jiayu Lu  1 , Yajing Hou  1 , Yuexin Lv  1 , Cheng Wang  1 , Huaizhen He  2
Affiliations

Azelastine inhibits viropexis of SARS-CoV-2 spike pseudovirus by binding to SARS-CoV-2 entry receptor ACE2

Shuai Ge et al. Virology. 2021 Aug.

Abstract

A recent study have reported that pre-use of azelastine is associated with a decrease in COVID-19 positive test results among susceptible elderly people. Besides, it has been reported that antihistamine drugs could prevent viruses from entering cells. The purpose of this study is to investigate whether azelastine have antiviral activity against SARS-CoV-2 in vitro and the possible mechanism. Here, we discovered antihistamine azelastine has an affinity to ACE2 by cell membrane chromatography (CMC); Then we determined the equilibrium dissociation constant (KD) of azelastine-ACE2 as (2.58 ± 0.48) × 10-7 M by surface plasmon resonance (SPR). The results of molecular docking showed that azelastine could form an obvious hydrogen bond with Lys353. The pseudovirus infection experiments showed that azelastine effectively inhibited viral entry (EC50 = 3.834 μM). Our work provides a new perspective for the screening method of drug repositioning for COVID-19, and an attractive and promising drug candidate for anti-SARS-CoV-2.

Keywords: ACE2; Antihistamine; Azelastine; Drug repurposing; SARS-CoV-2.

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Conflict of interest statement

All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
The binding character of azelastine with ACE2. (A)The protein expression level of NC-HKE293T and ACE2h. (B) The chromatogram of azelastine on the HEK293T/CMC and ACE2h/CMC model. (C) Binding response curves and KD of azelastine to ACE2 protein by SPR. Experiments were repeated three times.
Fig. 2
Fig. 2
Molecular docking identifies possible binding pockets for azelastine in ACE2. (A) Structures of azelastine. (B) Docked pose of azelastine at ACE2 protein (inset: conformation of azelastine showing important interaction with the receptor at the active site). Active residues involved in binding are displayed as sticks in purple, with hydrogen bonds shown as yellow dashed lines. (C) Surface representation of the best ranked docking pose of azelastine in ACE2 binding pocket.
Fig. 3
Fig. 3
Inhibiton of SARS-CoV-2 by azelastine. (A) Cell viability after incubation of ACE2h cells with azelastine for 24 h. (B) The entance of SARS-CoV-2 spike pseudovirus into ACE2h cells after treated with different concentration azelastine. (C) Inhibition analysis of SARS-CoV-2 spike pseudovirus by different concentration of azelastine. The left and right Y-axis of the graphs represent the mean percentage of inhibition of virus viropexis and cytotoxicity of the ACE2h cells, respectively.
See this image and copyright information in PMC

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