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

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) x 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 mu M). 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.