Coronaviruses are a large family of viruses that cause upper-respiratory tract illnesses. Three coronaviruses have caused serious and fatal disease, including MERS-CoV, SARS-CoV-1, and SARS-CoV-2 (COVID-19). Despite similarities between coronaviruses, each virus differs in its transmissibility and pathogenicity. When coronaviruses are cultured with cells outside the human body, apoptosis or programmed cell death occurs. Researchers from the University of Hong Kong identify a potential link between apoptosis and the pathogenesis/development of coronaviruses. 

First, the authors tested a large panel of molecules that inhibit caspases, a family of enzymes that execute apoptosis. They found that inhibition of one particular caspase, caspase-6, dramatically reduced the replication of MERS-CoV, SARS-CoV-1, and SARS-CoV-2. Next, using animal and cell models, the authors found that inhibition of caspase-6 also reduced the expression of proinflammatory markers. Finally, the authors found that during coronavirus replication, caspase-6 dampens the interferon (IFN) pathway, which is the first line of host defense against coronavirus infection. Collectively, their results suggest that inhibiting caspase-6 during coronavirus replication restores IFN signaling and reduces viral replication. 

The results of the present study are exciting and suggest that caspase-6 inhibition may serve as a treatment for pathogenic coronaviruses. However, follow-up studies in multiple animal models are required to refine the efficacy and toxicity of caspase-6 inhibition.  

Managing Correspondent: Alex Lish 

Original Journal Article: “Coronaviruses exploit a host cysteine-aspartic protease for replication” , Nature 

Image Credit: Pixabay 

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