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. 2025 Feb 10;80(9-10):539-548.
doi: 10.1515/znc-2024-0223. Print 2025 Sep 25.

Assessing the molecular interaction between a COVID-19 drug, nirmatrelvir, and human serum albumin: calorimetric, spectroscopic, and microscopic investigations

Mujaheed Abubakar  1   2 , Ahmad Fadhlurrahman Ahmad Hidayat  1 , Adyani Azizah Abd Halim  3 , Kushagra Khanna  4 , Mohammed Suleiman Zaroog  5 , Mogana Sundari Rajagopal  4 , Saad Tayyab  4
Affiliations

Assessing the molecular interaction between a COVID-19 drug, nirmatrelvir, and human serum albumin: calorimetric, spectroscopic, and microscopic investigations

Mujaheed Abubakar et al. Z Naturforsch C J Biosci. .

Abstract

The research examined the molecular interaction between nirmatrelvir (NIR), a drug used to treat COVID-19, and human serum albumin (HSA) using various techniques, viz., isothermal titration calorimetry (ITC), absorption, fluorescence, CD spectroscopy, and atomic force microscopy (AFM). ITC analysis showed that the NIR-HSA system possessed a moderate binding affinity, with a K a value of 6.53 ± 0.23 × 104 M-1 at a temperature of 300 K. The thermodynamic values demonstrated that the NIR-HSA complex was stabilized by hydrophobic contacts, hydrogen bonds, and van der Waals forces. The research also discovered modifications in the UV-Vis absorption spectrum of the protein as well as swelling of the HSA molecule when exposed to NIR, based on AFM results. The three-dimensional fluorescence spectral data indicated changes in the microenvironment around HSA's Trp and Tyr residues. Alterations in the protein structure (both secondary and tertiary structures) of HSA after NIR binding were verified using CD spectral studies in the far-UV and near-UV regions. The identification of the NIR binding site in subdomain IB (Site III) of HSA was predicted through competitive displacement experiments.

Keywords: COVID 19 drug; human serum albumin; infectious disease; isothermal titration calorimetry; nirmatrelvir.

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