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Updated: Apr 21, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Computational Studies on the Structures, Properties, and Pharmacodynamic Characteristics of Nirmatrelvir, its
Qiang Dai1, Yanni Wang2, Hong Li2
1The Oncology Chemotherapy Department of Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325200, Zhejiang, China.
Introduction:
The early COVID-19 pandemic underscored the urgent need for safe, effective antivirals.
Methods:
Thirty-three Nirmatrelvir analogs were computationally screened using DFT-based geometry optimization, IR/NMR/UV-Vis/ECD spectral simulation (with solvent effects), conceptual DFT reactivity analysis, drug-likeness assessment, and molecular docking against SARS-CoV-2 Mpro.
Results:
The data showed consistent structural stability across solvents; electrostatic potential maps revealed key polar regions near the 2-pyrrolidinone/amide oxygens and hydrogens; seven compounds exhibited balanced stability and reactivity; nine showed Nirmatrelvir-like pharmacodynamic profiles; among them, N3-SR4 stood out for its synthetic feasibility, favorable molecular descriptors, and strong Mpro binding affinity.
Discussion:
The electronic structure, reactivity indices, pharmacokinetic parameters, and molecular docking results all indicate that the synthesized intermediates exhibit a high degree of similarity to the target compounds in key physicochemical and biological activity characteristics.
Conclusion:
These findings support N3-SR4 as a promising candidate for further experimental validation.
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