Targeting viral proteins to disrupt replication is an important approach in developing a therapeutic treatment against SARS-CoV-2 infection. Ideally, one can target highly conserved viral proteins that are unlikely to acquire resistance as the outbreak progresses. Recent studies report SARS-CoV-2 genomic variations in over 10% of isolated sequences, with the most frequent mutations being P323L in NSP12 and D641G in the spike protein . In contrast, NSP15, an RNA uridylate-specific endoribonuclease (with a C-terminal region homologous to EndoU enzymes), is highly conserved, making it an attractive target for drug development. NSP15-like endoribonucleases are found in all coronavirus family members, suggesting its endonuclease function is critical for the viral life cycle. The amino-acid sequence alignment of NSP15 from SARS-CoV and SARS-CoV-2 showed 88% sequence identity and 95% sequence similarity .