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bioRxiv · 10.1101/2022.09.09.507342

Targeting intracellular Neu1 for Coronavirus Infection Treatment

Yang, D.·Wu, Y.·Turan, I.·Keil, J.·Li, K.·Chen, M. H.·Liu, R.·Wang, L.·Sun, X.-L.·Chen, G.
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Abstract

There are no effective therapies for COVID-19 or antivirals against SARS-CoV-2. Furthermore, current vaccines appear less efficacious for new SARS-CoV-2 variants. Thus, there is an urgent need to better understand the virulence mechanisms of SARS-CoV-2 and the host response to develop therapeutic agents. Here, we show host Neu1 regulates coronavirus replication by controlling sialylation on coronavirus nucleocapsid protein. Coronavirus nucleocapsid proteins in COVID-19 patients and in coronavirus HCoV-OC43-infected cells were heavily sialylated; this sialylation controlled the RNA binding activity and replication of coronavirus. Neu1 overexpression increased HCoV-OC43 replication, whereas Neu1 knockdown reduced HCoV-OC43 replication. Moreover, a newly developed Neu1 inhibitor, Neu5Ac2en-OAcOMe, selectively targeted intracellular sialidase, which dramatically reduced HCoV-OC43 and SARS-CoV-2 replication in vitro and rescued mice from HCoV-OC43 infection-induced death. Our findings suggest that Neu1 inhibitors could be used to limit SARS-CoV-2 replication in patients with COVID-19, making Neu1 a potential therapeutic target for COVID-19 and future coronavirus pandemics.

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Yang, D., Wu, Y., Turan, I., Keil, J., Li, K., Chen, M. H., Liu, R., Wang, L., Sun, X.-L., Chen, G.. 2022-09-11. Targeting intracellular Neu1 for Coronavirus Infection Treatment. https://doi.org/10.1101/2022.09.09.507342

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