Structure and Inhibitor Development of Coronavirus Main Protease NSP5

Shani Xiangyi Wang

2025

Abstract

The global health crisis triggered by COVID-19, a SARS-CoV-2 virus, has presented unparalleled challenges on the global health system, resulting in nearly 770 million infections and more than 7 million fatalities by the end of 2024. Despite significant advancements in vaccines and therapeutic interventions, the continuous emergence of viral variants underscores the urgent need for effective antiviral therapies. The non-structural protein (NSP) 5, a key enzyme for viral replication, has emerged as promising target for drug development due to its critical role in viral polyprotein cleavage and high specificity, lacking homologs in human cells. This article provides a methodical and comprehensive overview of NSP5 structural and functional characteristics, along with recent development of NSP5 inhibitor discovery. Clinically approved inhibitors, such as Paxlovid (Nirmatrelvir) and Xocova (Ensitrelvir), have demonstrated significant efficacy in reducing severe disease outcomes and mortality rates. However, challenges such as viral mutations, drug resistance, and pharmacokinetic limitations remain obstacles to long-term therapeutic success. The integration of advanced computational strategies, including structure-based drug design (SBDD), ligand-based drug design (LBDD), and artificial intelligence (AI)-driven approaches, has accelerated the discovery and optimization of novel NSP5 inhibitors. Additionally, multi-target synergistic therapies and innovative drug design strategies offer promising avenues to enhance antiviral efficacy and overcome resistance. This review also highlights the importance of rigorous efficacy evaluations to ensure the safety, pharmacokinetic stability and clinical viability of lead compounds. By consolidating existing knowledge and exploring future directions, this work aims to contribute to the ongoing development of next-generation antiviral therapies, ultimately strengthening global management of COVID-19 and preparedness for future coronavirus pandemics.

Paper Citation

in Harvard Style

Wang S. (2025). Structure and Inhibitor Development of Coronavirus Main Protease NSP5. In Proceedings of the 1st International Conference on Biomedical Engineering and Food Science - Volume 1: BEFS; ISBN 978-989-758-789-4, SciTePress, pages 82-89. DOI: 10.5220/0014401000004933

in Bibtex Style

@conference{befs25,
author={Shani Wang},
title={Structure and Inhibitor Development of Coronavirus Main Protease NSP5},
booktitle={Proceedings of the 1st International Conference on Biomedical Engineering and Food Science - Volume 1: BEFS},
year={2025},
pages={82-89},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0014401000004933},
isbn={978-989-758-789-4},
}

in EndNote Style

TY - CONF

JO - Proceedings of the 1st International Conference on Biomedical Engineering and Food Science - Volume 1: BEFS
TI - Structure and Inhibitor Development of Coronavirus Main Protease NSP5
SN - 978-989-758-789-4
AU - Wang S.
PY - 2025
SP - 82
EP - 89
DO - 10.5220/0014401000004933
PB - SciTePress