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P97/VCP as a therapy target for developing drugs against human coronavirus

ABSTRACT: Understanding how human coronavirus dysregulate host proteome during infection in human cells will identify general pathways that are common to coronavirus infection. NMS-873 is an allosteric p97/VCP ATPase inhibitor and was show to have antiviral effect in multiple viruses including SARS-CoV2. We first demonstrated that genetic knock down of p97 reduced HCoV-229E, HCoV-OC43 infection and secretion. To investigate how p97/VCP assists virus infection, we used unbiased quantitative proteomics to compare dysregulated proteomes caused by HCoV-229E, HCoV-OC43 and SARS-CoV2 infection. We then compared dysregulated proteomes after HCoV-229E and HCoV-OC43 infection with and without p97 knockdown. Moreover, we elucidated the impact of p97 on different stages of viral life cycle using two potent p97 inhibitors, CB-5083 and NMS-873 and demonstrate their can block HCoV replication. Together, our data provide insights to repurpose potential cancer drugs that target the essential host protein p97/VCP.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Coronavirus Infectious Disease

SUBMITTER: Shan Li

LAB HEAD: Tsui-Fen Chou

PROVIDER: PXD026216 | Pride | 2021-11-03

REPOSITORIES: Pride

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