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.

doi:10.1101/2022.01.22.477323

bioRxiv · 10.1101/2022.01.22.477323

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.

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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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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.. 2022-01-25. Harringtonine has the effects of double blocking SARS-CoV-2 membrane fusion. https://doi.org/10.1101/2022.01.22.477323

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