Liang Taizhen, Qiu Jiayin, Niu Xiaoge, Ma Qinhai, Zhou Chenliang, Chen Pei, Zhang Qiao, Chen Meiyun, Yang Zifeng, Liu Shuwen, Li Lin
Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
School of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.
Front Pharmacol. 2021 Jan 14;11:603830. doi: 10.3389/fphar.2020.603830. eCollection 2020.
The global spread of the novel coronavirus SARS-CoV-2 urgently requires discovery of effective therapeutics for the treatment of COVID-19. The spike (S) protein of SARS-CoV-2 plays a key role in receptor recognition, virus-cell membrane fusion and virus entry. Our previous studies have reported that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) serves as a viral entry inhibitor to prevent several kinds of virus infection. Here, our results reveal that HP-OVA can effectively inhibit SARS-CoV-2 replication and S protein-mediated cell-cell fusion in a dose-dependent manner without obvious cytopathic effects. Further analysis suggests that HP-OVA can bind to both the S protein of SARS-CoV-2 and host angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and disrupt the S protein-ACE2 interaction, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that HP-OVA can serve as a potential therapeutic agent for the treatment of deadly COVID-19.
新型冠状病毒SARS-CoV-2在全球的传播迫切需要发现治疗COVID-19的有效疗法。SARS-CoV-2的刺突（S）蛋白在受体识别、病毒-细胞膜融合及病毒进入过程中起关键作用。我们之前的研究报道，3-羟基邻苯二甲酸酐修饰的鸡卵清蛋白（HP-OVA）作为一种病毒进入抑制剂可预防多种病毒感染。在此，我们的结果显示，HP-OVA能以剂量依赖的方式有效抑制SARS-CoV-2复制及S蛋白介导的细胞-细胞融合，且无明显细胞病变效应。进一步分析表明，HP-OVA可与SARS-CoV-2的S蛋白及宿主血管紧张素转换酶2（ACE2，SARS-CoV-2的功能性受体）结合，并破坏S蛋白-ACE2相互作用，从而表现出对SARS-CoV-2感染的抑制活性。总之，我们的研究结果表明，HP-OVA可作为治疗致命性COVID-19的潜在治疗药物。
