Prokaryotes have evolved diverse defense strategies against viral infection, including foreign nucleic acid degradation by CRISPR-Cas systems and DNA and RNA synthesis inhibition through nucleotide pool depletion. Here, we report an antiviral mechanism of type III CRISPR-Cas–regulated adenosine triphosphate (ATP) depletion in which ATP is converted into inosine triphosphate (ITP) by CRISPR-Cas–associated adenosine deaminase (CAAD) upon activation by either cA 4 or cA 6 , followed by hydrolysis into inosine monophosphate (IMP) by Nudix hydrola...