Abstract:
The Coronavirus Disease 2019 (COVID-19) pandemic and the subsequent increase in respiratory viral infections highlight the need for broad-spectrum antivirals to enable a quick and efficient reaction to current and emerging viral outbreaks. We previously demonstrated that the antihistamine azelastine hydrochloride (azelastine-HCl) exhibited in vitro antiviral activity against SARS-CoV-2. Furthermore, in a phase 2 clinical study, a commercial azelastine-containing nasal spray significantly reduced the viral load in SARS-CoV-2-infected individuals. Here, we evaluate the efficacy of azelastine-HCl against additional human coronaviruses, including the SARS-CoV-2 omicron variant and a seasonal human coronavirus, 229E, through in vitro infection assays, with azelastine showing a comparable potency against both. Furthermore, we determined that azelastine-HCl also inhibits the replication of Respiratory syncytial virus A (RSV A) in both prophylactic and therapeutic settings. In a human 3D nasal tissue model (MucilAirTM-Pool, Epithelix), azelastine-HCl protected tissue integrity and function from the effects of infection with influenza A H1N1 and resulted in a reduced viral load soon after infection. Our results suggest that azelastine-HCl has a broad antiviral effect and can be considered a safe option against the most common respiratory viruses to prevent or treat such infections locally in the form of a nasal spray that is commonly available globally.
摘要:
2019年冠状病毒病(COVID-19)大流行和随后呼吸道病毒感染的增加凸显了广谱抗病毒药物的必要性,以便对当前和新出现的病毒爆发做出快速有效的反应。我们先前证明了抗组胺剂盐酸氮卓斯汀(盐酸氮卓斯汀)对SARS-CoV-2具有体外抗病毒活性。此外,在一项2期临床研究中,市售的含氮卓斯汀的鼻喷雾剂可显着降低SARS-CoV-2感染个体的病毒载量。这里,我们评估盐酸氮卓斯汀对其他人类冠状病毒的疗效,包括SARS-CoV-2omicron变种和季节性人类冠状病毒,229E,通过体外感染试验,氮卓斯汀对两者都表现出相当的效力。此外,我们确定盐酸氮卓斯汀在预防和治疗环境中也抑制呼吸道合胞病毒A(RSVA)的复制.在人类3D鼻组织模型(MucilAirTM-Pool,Epithelix),盐酸氮卓斯汀保护组织完整性和功能免受甲型H1N1流感感染的影响,并导致感染后很快病毒载量降低。我们的结果表明,盐酸氮卓斯汀具有广泛的抗病毒作用,可以被认为是针对最常见的呼吸道病毒的安全选择,以全球普遍可用的鼻喷雾剂形式预防或治疗局部感染。