Abstract
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.
Highlights
Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread worldwide (Kuan et al, 2016; Sharma et al, 2020; Zhou et al, 2020)
As demonstrated in previous studies (Yin et al, 2018), the pseudotyped system of the SARS-CoV-2 S protein is a classic model that mimics the process of viral entry and studies the interaction of SARS-CoV-2 and host cells
To investigate whether hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) has the same effect on SARS-CoV, which is closely related to SARS-CoV-2 and employs angiotensinconverting enzyme 2 (ACE2) for cell entry, we conducted a pilot experimental test in vitro on the antiSARS-CoV PsV activity using both 293T/ACE2 cells and Vero E6 cells
Summary
Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread worldwide (Kuan et al, 2016; Sharma et al, 2020; Zhou et al, 2020). Similar to other two coronavirus strains, including SARS-CoV and Middle East respiratory syndrome coronavirus (MERSCoV), cell entry of SARS-CoV-2 is the first step of crossspecies transmission. SARS-CoV-2 contains four important structural proteins: the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. The S protein on the surface of SARS-CoV-2 cells is composed of a receptor-binding unit S1 and a membrane-fusion unit S2 (Rota et al, 2003; Walls et al, 2020). The interactions between the S protein and the ACE2 receptor play an important role in viral entry into host cells (Wu et al, 2012; Huo et al, 2020a; Tai et al, 2020). It might be a potential approach to screen special antibodies or small-molecule inhibitors for blocking the RBD and ACE2 interaction and preventing virus infection (Chu et al, 2008; Du et al, 2009; Huo et al, 2020b)
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