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

被引：0

作者：

Abubakar, Mujaheed ^{[2
,3
]}

Hidayat, Ahmad Fadhlurrahman Ahmad ^{[2
]}

Abd Halim, Adyani Azizah ^{[4
]}

Khanna, Kushagra ^{[1
]}

Zaroog, Mohammed Suleiman ^{[5
]}

Rajagopal, Mogana Sundari ^{[1
]}

Tayyab, Saad ^{[1
]}

机构：

[1] UCSI Univ, Fac Pharmaceut Sci, Kuala Lumpur 56000, Malaysia

[2] Univ Malaya, Inst Biol Sci, Fac Sci, Kuala Lumpur 50603, Malaysia

[3] Sule Lamido Univ, Fac Nat & Appl Sci, Dept Biol Sci, Kafin Hausa, Nigeria

[4] Univ Malaya, Fac Dent, Dept Oral & Craniofacial Sci, Kuala Lumpur 50603, Malaysia

[5] Northern Border Univ, Fac Appl Med Sci, Ar Ar, Saudi Arabia

来源：

ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES | 2025年

关键词：

nirmatrelvir; human serum albumin; infectious disease; COVID; 19; drug; isothermal titration calorimetry; ATOMIC-FORCE MICROSCOPY; LIGAND-BINDING; PROTEIN; FLAVONOIDS; INHIBITOR; INSIGHTS; GROWTH; SITES; ACID; BSA;

D O I：

10.1515/znc-2024-0223

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 x 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.

引用

页数：10