SARS-CoV-2 nonstructural protein 15 endoribonuclease (Nsp15)

SARS-CoV-2 nonstructural protein 15 (Nsp15) is a uridylate-specific endoribonuclease (NendoU) that plays a critical role in the viral life cycle by facilitating immune evasion (UniProt P0DTD1). It functions by cleaving poly-uridine sequences at the 5' ends of negative-strand viral RNA, thereby preventing the activation of host pattern recognition receptors such as MDA5, which would otherwise trigger a robust interferon-mediated antiviral response (Hackbart et al., 2020). Structurally, Nsp15 exists as a hexamer, and its catalytic activity is dependent on manganese ions (Kim et al., 2020). Because Nsp15 is highly conserved among coronaviruses and lacks a direct human homolog, it is considered a promising target for the development of broad-spectrum antiviral therapies. Small molecules like Tipiracil and Ebselen have been identified as potential inhibitors that disrupt its enzymatic activity, potentially restoring the host's ability to detect and clear the virus (Zhang et al., 2021).

Other names

Nsp15NendoUUridylate-specific endoribonucleaseNon-structural protein 15Endoribonuclease Nsp15

Inhibition of the uridylate-specific endoribonuclease activity to prevent viral immune evasion and suppress viral replication.