In Silico Exploration of Potential Inhibitors Targeting Sars-Cov-2 Non-Structural Protein 15 (Nsp15): A Comprehensive Overview of Current Research Publisher Pubmed



Yazdani B ; Sirous H ; Farzam F ; Ansarizadeh S ; Karimi Taheri M ; Pourmohammadhosseini G ; Noei M ; Daneshipour K ; Shakeri D ; Houshangi M ; Calderone V ; Brogi S
Source: Chemical Biology and Drug Design Published:2025

Abstract

The SARS-CoV-2 nonstructural protein 15 (Nsp15) is an endoribonuclease that plays a critical role in viral replication and immune evasion through its NendoU domain. The unique enzymatic mechanism of Nsp15 has attracted considerable attention as a potential therapeutic target, and the identification of its inhibitors could facilitate the development of novel antiviral agents against coronaviruses. Although biochemical and structural studies have provided important insights into Nsp15 function, no comprehensive review has yet focused on computational approaches applied to the discovery of Nsp15 inhibitors. Consequently, this study aims to address this gap by summarizing recent in silico research focused on the structure, function, and inhibition of Nsp15. Special attention is given to inhibitors derived from both natural and synthetic sources, as well as their binding interactions and predicted pharmacological potential. By integrating current computational findings, this review highlights novel prospects for the rational design of Nsp15-targeted therapeutics to combat SARS-CoV-2 and other related pathogenic coronaviruses. © 2025 John Wiley & Sons Ltd.