Harringtonine has the effects of double blocking SARS-CoV-2 membrane fusion
Hu, S.; Wang, N.; Chen, S.; Ding, Q.; Wang, C.; Ma, W.; Zhang, X.; Wu, Y.; Lv, Y.; Xue, Z.; Bai, H.; Ge, S.; He, H.; Lu, W.; Zhang, T.; Ding, Y.; Liu, R.; Han, S.; Zhan, Y.; Zhan, G.; Guo, Z.; Zhang, Y.; Lu, J.; Gao, J.; Jia, Q.; Wang, Y.; Lu, S.; Zhang, H.; He, L.
Show abstract
Fusion with host cell membrane is the main mechanism of infection of SARS-CoV-2. Here, we propose a new strategy to double block SARS-CoV-2 membrane fusion by using Harringtonine (HT), a small-molecule antagonist. By using cell membrane chromatography (CMC), we found that HT specifically targeted the SARS-CoV-2 S protein and host cell TMPRSS2, and then confirmed that HT can inhibit pseudotyped virus membrane fusion. Furthermore, HT successfully blocked SARS-CoV-2 infection, especially in the delta and Omicron mutant. Since HT is a small-molecule antagonist, it is minimally affected by the continuous variation of SARS-CoV-2. Our findings show that HT is a potential small-molecule antagonist with a new mechanism of action against SARS-CoV-2 infection, and thus HT mainly targets the S protein, and thus, greatly reduces the damage of the S proteins autotoxicity to the organ system, has promising advantages in the clinical treatment of COVID-19.
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