The high frequency of RNA virus mutations and outbreaks of emerging RNA viral infections are challenging public health issues. Developing a drug that can overcome viral mutations with broad-spectrum antiviral activity is an unmet need.
Scientists at National Taiwan University have observed RNA synthesis by RNA viruses at mitochondria/endoplasmic reticulum (Mito/ER) spheres in infected cells, accompanied by the leakage of a mitochondrial nuclease, ENDOG, into the cytosol.
ENDOG released from mitochondria can degrade viral RNAs as an antiviral factor. However, the released ENDOG can also translocate to nuclei and cause nuclear DNA damage.
Researchers then engineered an ENDOG anchored to the mitochondrial surface, namely MOM-ENDOG, whose expression efficiently degrades viral RNA transcripts synthesized at mitochondrial sites without causing nuclear DNA damage. Delivery of modified mRNA encoding wild-type, but not catalytic-dead, MOM-ENDOG markedly suppresses the propagation of VSV, influenza, dengue and Zika viruses.
"This modified mRNA encoding mitochondrial site-specific viral RNA degrader is a broad-spectrum antiviral agent and its mode of action would not be affected by the viral mutations," said Zee-Fen Chang, chair professor at the Center of Nucleic Acid Medicine, National Taiwan University College of Medicine and corresponding author of the study published in Nature Communications.
Provided by National Taiwan University