Biological and computational assessments of thiazole derivative-reinforced bile salt enriched nano carriers: a new gate in targeting SARS-CoV-2 spike protein

Abstract

There is merit in investigating novel therapeutic molecules that hit vital targets during the viral infection cycle i.e. disrupting the interaction between SARS-CoV-2's spike glycoprotein and the host's angiotensin converting enzyme 2 (ACE2) receptor, potentially offering new avenues for treatment. Accordingly, lipid-based vesicular systems like liposomes or niosomes are frequently utilized to overcome these hurdles. Thus, chemically synthesized compounds were encapsulated within PEGylated bilosomes (PBs) to improve their solubility and intestinal permeability, thereby enhancing their anti-SARS-CoV-2 effectiveness. The formulae were prepared according to 2³ full factorial design which was also used to explore the impact of the change in predetermined formulation variables on the properties of the prepared vesicles (entrapment efficiency EE%, particle size PS, and zeta potential ZP). Additionally, the optimized formula (F4) which is composed of 3% bile salt (BS), 40 mg 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE) and sodium deoxycholate (SDC) as a bile salt, was selected as an optimum formula with desirability value 0.674 using Design Expert® software. Both the in vitro release and ex vivo experiments results confirmed the significant superiority of the F4 over the drug dispersion. Both cytotoxicity and anti-SARS-CoV-2 activity of all examined compound-loaded PBs (PB3a–PB3g) were assessed in Vero E6 cells via MTT assay. Both compounds PB3c and PB3g displayed the highest IC₅₀ values (0.71 and 1.25 μg mL⁻¹, respectively) ensuring their superior antiviral potential. Moreover, it was revealed that PB3c demonstrated more than 80% virucidal activity and over 80% inhibition of viral adsorption with little effect on the viral replication ∼(5–10%). Moreover, molecular docking and dynamic studies were conducted to pursue the binding affinities of the investigated compounds towards the ACE2 target of the SARS-CoV-2 spike protein, assuring their feasible inhibitory potential. Collectively, the investigated compound-loaded PBs can be treated as promising lead drug delivery panels for COVID-19 management.