Warning: This is a preliminary report that has not been peer-reviewed. It should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information.

Heaton BE, Trimarco JD, Hamele CE, Harding AT, Tata A, Zhu X, Tata PR, Smith CM, Heaton NS, RosasLemus M, Saint N, Foster IT, Michalska K, Satchell KJ, Joachimiak A, Li H, Zhang Z, Wang R, Du P, Zong Y, Yin F, Zhang W, Peng Y, Lin H, Zhang R, Chen W, Gao Q, Cao Y, Zhong H, Douglas I, Goldacre B

Antiviral therapeutics against SARS-CoV-2 are needed to treat the pandemic disease COVID-19. Pharmacological targeting of a host factor required for viral replication can suppress viral spread with a low probability of viral mutation leading to resistance. Here, we performed a genome-wide screen in human lung epithelial cells to identify potential ...

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host therapeutic targets. We report that the kinase SRPK1, together with the closely related SRPK2, are jointly essential for SARS-CoV-2 replication; inhibition of SRPK1/2 with small molecules led to a dramatic decrease (more than 100,000-fold) in SARS-CoV-2 virus production in immortalized and primary human lung cells. Subsequent biochemical studies revealed that SPRK1/2 phosphorylate the viral nucleocapsid (N) protein at sites highly conserved across human coronaviruses and, due to this conservation, even a distantly related coronavirus was highly sensitive to an SPRK1/2 inhibitor. Together, these data suggest that SRPK1/2-targeted therapies may be an efficacious strategy to prevent or treat COVID-19 and other coronavirus-mediated diseases.

Date: Aug. 14, 2020

Status: Preliminary Report

View Source: doi: 10.1101/2020.08.14.251207

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