Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of <i>N</i>-(5-nitrothiazol-2-yl)-carboxamido candidates: <i>in vitro</i> and <i>in silico</i> studies
Creators: name: Al-Karmalawy, Ahmed A.
name: El-Gamil, Dalia S.
name: El-Shesheny, Rabeh
name: Sharaky, Marwa
name: Alnajjar, Radwan
name: Kutkat, Omnia
name: Moatasim, Yassmin
name: Elagawany, Mohamed
name: Al-Rashood, Sara T.
name: Binjubair, Faizah A.
name: Eldehna, Wagdy M.
name: Noreddin, Ayman M.
name: Zakaria, Mohamed Y.
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biochemistry
subject: Space Science
subject: Microbiology
subject: FOS: Biological sciences
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Science Policy
subject: 69999 Biological Sciences not elsewhere classified
subject: 60506 Virology

description: In this article, emulsomes (EMLs) were fabricated to encapsulate the <i>N</i>-(5-nitrothiazol-2-yl)-carboxamido derivatives (<b>3a</b>–<b>3g</b>) in an attempt to improve their biological availability and antiviral activity. Next, both cytotoxicity and anti-SARS-CoV-2 activities of the examined compounds loaded EMLs (<b>F3a</b>–<b>g</b>) were assessed in Vero E6 cells via MTT assay to calculate the CC<sub>50</sub> and inhibitory concentration 50 (IC<sub>50</sub>) values. The most potent <b>3e</b>-loaded EMLs (<b>F3e</b>) elicited a selectivity index of 18 with an IC<sub>50</sub> value of 0.73 μg/mL. Moreover, <b>F3e</b> was selected for further elucidation of a possible mode of action where the results showed that it exhibited a combination of virucidal (&gt;90%), viral adsorption (&gt;80%), and viral replication (&gt;60%) inhibition. Besides, molecular docking and MD simulations towards the SARS-CoV-2 Mpro were performed. Finally, a structure–activity relationship (SAR) study focussed on studying the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide in addition to compound contraction on SARS-CoV-2 activity.HighlightsEmulsomes (EMLs) were fabricated to encapsulate the <i>N</i>-(5-nitrothiazol-2-yl)-carboxamido derivatives (<b>3a</b>–<b>3g</b>).The most potent <b>3e</b>-loaded EMLs (<b>F3e</b>) showed an IC<sub>50</sub> value of 0.73 μg/mL against SARS-CoV-2.F3e exhibited a combination of virucidal (&gt;90%), viral adsorption (&gt;80%), and viral replication (&gt;60%) inhibition.Molecular docking, molecular dynamics (MD) simulations, and MM-GBSA calculations were performed.Structure–activity relationship (SAR) study was discussed to study the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide on the anti-SARS-CoV-2 activity. Emulsomes (EMLs) were fabricated to encapsulate the <i>N</i>-(5-nitrothiazol-2-yl)-carboxamido derivatives (<b>3a</b>–<b>3g</b>). The most potent <b>3e</b>-loaded EMLs (<b>F3e</b>) showed an IC<sub>50</sub> value of 0.73 μg/mL against SARS-CoV-2. F3e exhibited a combination of virucidal (&gt;90%), viral adsorption (&gt;80%), and viral replication (&gt;60%) inhibition. Molecular docking, molecular dynamics (MD) simulations, and MM-GBSA calculations were performed. Structure–activity relationship (SAR) study was discussed to study the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide on the anti-SARS-CoV-2 activity.