The core polymerase complex of SARS-CoV-2 has become one promising antiviral drug target. It is the minimal scaffold to mediate the RNA synthesis and plays a central role in viral replication and transcription. It is composed of three non-structural proteins (nsp) (Fig. ), where nsp12 mainly conducts the RNA synthesis in the active site, and nsp7 and nsp8 serve as cofactors to stimulate RNA-dependent RNA polymerase (RdRp) activity . Since the outbreak of the pandemic, nucleotide analogs have been widely explored as potential inhibitors to terminate the RNA synthesis in SARS-CoV-2 RdRp .