In Silico Exploration of Potential Inhibitors Targeting <scp>SARS</scp> ‐ <scp>CoV</scp> ‐2 Non‐Structural Protein 15 (Nsp15): A Comprehensive Overview of Current Research
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.
Authors
- Behnaz Yazdani (ORCID: https://orcid.org/0000-0002-4243-1330)
- Hajar Sirous (ORCID: https://orcid.org/0000-0003-4311-9952)
- Farnoosh Farzam
- Mohammadjavad Karimi Taheri (ORCID: https://orcid.org/0000-0003-3345-7595)
- Simone Brogi (ORCID: https://orcid.org/0000-0001-9375-6242)
- Kosar Daneshipour (ORCID: https://orcid.org/0009-0000-7525-2489)
- Maryam Houshangi
- Shayan Ansarizadeh (ORCID: https://orcid.org/0009-0005-8254-4080)
- Ghazal Pourmohammad‐Hosseini (ORCID: https://orcid.org/0000-0003-2233-9358)
- Maryam Noei
- Danial Shakeri
Institutions
- University of Pisa (IT)
- Isfahan University of Medical Sciences (IR)
- Universitat de Vic - Universitat Central de Catalunya (ES)
- Tarbiat Modares University (IR)
- Islamic Azad University, Isfahan (IR)
- Jahrom University (IR)
- Jahrom University of Medical Sciences (IR)
- Federico II University Hospital (IT)
- Islamic Azad University Quchan (IR)
- Tehran University of Medical Sciences (IR)
- University of Naples Federico II (IT)
- University of Bologna (IT)
Publication Details
- Journal
- Chemical Biology & Drug Design
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1111/cbdd.70218
- Primary Topic
- Pharmacological Receptor Mechanisms and Effects
- Type
- article
- Field-Weighted Citation Impact
- 0.00