What is the impact of COVID-19 treatments targeting intracellular Neu1? biorxivpreprint uthsc SARSCoV2 COVID19 IntracellularNeu1
By Bhavana KunkalikarSep 14 2022Reviewed by Aimee Molineux In a recent study posted to the bioRxiv* preprint server, researchers assessed the impact of targeting intracellular Neu1 on severe acute respiratory syndrome coronavirus 2 infection.
The team employed mass spectrometry to study the N- and O-glycans on the nucleocapsid protein from the human coronavirus OC43 , a beta coronavirus that causes mild respiratory symptoms. A lectin blot was performed using samples immunoprecipitated from the serum of SARS-CoV-2-infected patients and healthy controls, as well as cell lysates infected with HCoV-OC43 and treated with anti-N protein antibodies.
Subsequently, cells were administered with or without sialidase for nucleic acid-binding experiments. Using THP-1 cell lines, the team assessed the role of endogenous sialidases in the sialylation of N protein. Related StoriesIn the presence of anti-N protein antibodies, a SARS-CoV-2 N protein formed a potent complex with 32-mer ssRNA and 32-mer ssDNA that was supershifted, demonstrating that this complex was exclusive to N protein. As anticipated, lysates of HEK293T cells transfected with an empty vector failed to bind 32-mer ssRNA and ssDNA. Furthermore, the amount of 32-mer ssDNA and ssRNA bound to N protein after sialidase treatment rose significantly.
In line with the knockdown effectiveness of shRNA, Neu1sh3 dramatically reduced HCoV-OC43 replication more than Neu1sh1 and Neu1sh2 did. N protein levels were also noticeably higher in Neu1 overexpressing cells than in Neu1 knockdown cells. These findings suggested that host Neu1 controlled HCoV-OC43 replication in THP-1 cells. The most effective protection was provided by Neu5Ac2en-OAcOMe, while viral neuraminidase inhibitors Zanamivir and oseltamivir displayed little inhibitory activity.
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