Design and Statistical Optimisation of Emulsomal Nanoparticles for Improved Anti-SARS-CoV-2 Activity of -(5-nitrothiazol-2-yl)-carboxamido Candidates: and Studies

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2023 Apr 24

PMID 37092260

Authors

Ahmed A Al-Karmalawy

Dalia S El-Gamil

Rabeh El-Shesheny

Marwa Sharaky

Radwan Alnajjar

Omnia Kutkat

Yassmin Moatasim

Mohamed Elagawany

Sara T Al-Rashood

Faizah A Binjubair

Wagdy M Eldehna

Ayman M Noreddin

Mohamed Y Zakaria

Affiliations

Soon will be listed here.

Abstract

In this article, emulsomes (EMLs) were fabricated to encapsulate the -(5-nitrothiazol-2-yl)-carboxamido derivatives (-) 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 (-) were assessed in Vero E6 cells via MTT assay to calculate the CC and inhibitory concentration 50 (IC) values. The most potent -loaded EMLs () elicited a selectivity index of 18 with an IC value of 0.73 μg/mL. Moreover, was selected for further elucidation of a possible mode of action where the results showed that it exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>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 -(5-nitrothiazol-2-yl)-carboxamido derivatives (-).The most potent -loaded EMLs () showed an IC value of 0.73 μg/mL against SARS-CoV-2.F3e exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>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.

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