Interaction of GC376, a SARS-COV-2 MPRO inhibitor, with model lipid membranes
Colloids and Surfaces B: Biointerfaces
; 220, 2022.
Article
in English
| EMBASE | ID: covidwho-2242220
ABSTRACT
Partitioning and effect of antiviral GC376, a potential SARS-CoV-2 inhibitor, on model lipid membranes was studied using dynamic light scattering (DLS), UV–VIS spectrometry, Excimer fluorescence, Differential scanning calorimetry (DSC) and Small- and Wide-angle X-ray scattering (SAXS/WAXS). Partition coefficient of GC376 between lipid and water phase was found to be low, reaching KP = 46.8 ± 18.2. Results suggest that GC376 partitions into lipid bilayers at the level of lipid head-groups, close to the polar/hydrophobic interface. Changes in structural and thermodynamic properties strongly depend on the GC376/lipid mole ratio. Already at lowest mole ratios GC376 induces increase of lateral pressures, mainly in the interfacial region of the bilayer. Hereby, the pre- and main-transition temperature of the lipid system increases, what is attributed to tighter packing of acyl chains induced by GC376. At GC376/DPPC ≥ 0.03 mol/mol we detected formation of domains with different GC376 content resulting in the lateral phase separation and changes in both, main transition temperature and enthalpy. The observed changes are attributed to the response of the system on the increased lateral stresses induced by partitioning of GC376. Obtained results are discussed in context of liposome-based drug delivery systems for GC376 and in context of indirect mechanism of virus replication inhibition.
Agilent 8453; calorimeter; FluoroMax 4; fluorometer; Litesizer 500; Nano DSC; spectrophotometer; ultraviolet spectrophotometer; 1 2 dipalmitoyl phosphatidylcholine; 2 dioleoyl phosphatidylcholine; biosynth carbosynth; coronavirus 3C protease; dipalmitoylphosphatidylcholine; protein; proteinase inhibitor; SARS-CoV-2 inhibitor gc376; unclassified drug; article; centrifugation; controlled study; crystallization; dispersity; drug bioavailability; enthalpy; fluorescence analysis; hydrodynamics; hydrophobicity; lipid bilayer; lipid membrane; nonhuman; particle size; partition coefficient; pH; photon correlation spectroscopy; Severe acute respiratory syndrome coronavirus 2; temperature; thermodynamics; ultraviolet spectrophotometry; X ray diffraction
Full text:
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Colloids and Surfaces B: Biointerfaces
Year:
2022
Document Type:
Article
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