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

  • Mujaheed Abubakar , Ahmad Fadhlurrahman Ahmad Hidayat , Adyani Azizah Abd Halim , Kushagra Khanna , Mohammed Suleiman Zaroog , Mogana Sundari Rajagopal and Saad Tayyab ORCID logo EMAIL logo
Published/Copyright: February 10, 2025
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Zeitschrift für Naturforschung C
From the journal Zeitschrift für Naturforschung C Volume 80 Issue 9-10

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: nirmatrelvir; human serum albumin; infectious disease; COVID 19 drug; isothermal titration calorimetry
Corresponding author: Saad Tayyab, Faculty of Pharmaceutical Sciences, UCSI University, 56000 Kuala Lumpur, Malaysia, E-mail:

Funding source: UCSI University

Award Identifier / Grant number: REIG grant (REIG-FPS-2023/039)

Acknowledgments

The authors express their gratitude to the Institute of Biological Sciences, Faculty of Science and Faculty of Dentistry, Universiti Malaya for the essential support and resources that significantly contributed to their research. Additionally, they acknowledge the financial support from the UCSI University REIG grant (REIG-FPS-2023/039) sanctioned to Saad Tayyab.

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: Investigation, formal analysis, original draft: Mujaheed Abubakar; investigation, formal analysis: Ahmad Fadhlurrahman Ahmad Hidayat; supervision: Adyani Azizah Abd Halim; supervision: Kushagra Khanna; review and editing: Mohammed Suleiman Zaroog; fund acquisition, supervision: Mogana Sundari Rajagopal; conceptualization, fund acquisition, visualization, supervision, final draft: Saad Tayyab.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: UCSI University REIG grant (REIG-FPS-2023/039).

  7. Data availability: Data will be made available on reasonable request from the corresponding author.

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Received: 2024-10-14
Accepted: 2025-01-18
Published Online: 2025-02-10
Published in Print: 2025-09-25

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/znc-2024-0223
Keywords for this article
nirmatrelvir; human serum albumin; infectious disease; COVID 19 drug; isothermal titration calorimetry

Articles in the same Issue

  1. Frontmatter
  2. Review Articles
  3. Phyto-pharmaceuticals as a safe and potential alternative in management of psoriasis: a review
  4. Latest developments in biomaterial interfaces and drug delivery: challenges, innovations, and future outlook
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  8. Essential oil composition, in vitro antidiabetic, cytotoxicity, antimicrobial, antioxidant activity, and in silico molecular modeling analysis of secondary metabolites from Justicia schimperiana
  9. French marigold (Tagetes patula) flavonoid extract-based priming ameliorates initial drought stress on Oryza sativa var indica, cultivar Satabdi (IET4786): a sustainable approach to avoid initial drought stress
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  11. Insight into in vitro thymidine phosphorylase and in silico molecular docking studies: identification of hybrid thiazole bearing Schiff base derivatives
  12. In vivo evaluation of the antinociceptive effects of novel methylsulfonyl group-containing compounds
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