Thapsigargin: key to new host-directed coronavirus antivirals?

Despite the great success of vaccines that protect against RNA virus infections, and the development and clinical use of a limited number of RNA virus-specific drugs, there is still an urgent need for new classes of antiviral drugs against circulating or emerging RNA viruses. To date, it has proved difficult to efficiently suppress RNA virus replication by targeting host cell functions, and there are no approved drugs of this type. This opinion article discusses the recent discovery of a pronounced and sustained antiviral activity of the plant-derived natural compound thapsigargin against enveloped RNA viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), and influenza A virus.

Multi-level inhibition of coronavirus replication by chemical ER stress.

Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. The ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types including primary differentiated human bronchial epithelial cells, (partially) reverses the virus-induced translational shut-down, improves viability of infected cells and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP.

PTPRG and PTPRC modulate nilotinib response in chronic myeloid leukemia cells.

The introduction of second-generation tyrosine kinase inhibitors (TKIs) targeting the protein-tyrosine kinase (PTK) BCR-ABL1 has improved treatment response in chronic myeloid leukemia (CML). However, in some patients response still remains suboptimal. Protein-tyrosine phosphatases (PTPs) are natural counter-actors of PTK activity and can affect TKI sensitivity, but the impact of PTPs on treatment response to second-generation TKIs is unknown.