Narrow Results

The antioxidative activity and free radical scavenging potency of usnic acid towards eight selected free radical species are examined. The thermodynamic parameters in the absence of harmful free radicals are used to predict the most favorable mechanism of antioxidative action. The reaction enthalpies are used to define the most probable mechanism of free radical scavenging in the presence of free radical species. The obtained results indicate that the favorable mechanism of antiradical action is dependent both on the polarity of solvents and the nature of free radical species. From the achieved results, it is clear that Sequential Proton Loss Electron Transfer (SPLET) is the most probable for antioxidative action in water and methanol, while competition between SPLET and Hydrogen Atom Transfer (HAT) is presented in benzene. The free radical scavenging of eight free radical species under investigation is possible, and the most believable mechanism of action is SPLET, in all three investigated solvents. Since usnic acid exhibits significant radical scavenging activity that affects the maintenance of redox hemostasis, its inhibitory potency toward COVID-19 targeted proteins molecular docking study is performed. The obtained results indicate that usnic acid has the potential to inhibit the functional proteins of SARS-CoV-2.

Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic disease and dengue shock syndrome (DSS), transmitted predominantly in tropical and subtropical regions by Aedes aegypti. It infects millions of people and causes thousands of deaths each year, but there is no antiviral drug against DENV. Usnic acid lately piqued the interest of researchers for extraordinary biological characteristics, including antiviral activity. Based on high larvicidal activities against Aedes aegypti, this study aims to search usnic acid derivatives as novel anti-DENV agents through a combination of ligand-based and pharmacophore-based virtual screening. One hundred and sixteen (116) usnic acid derivatives were obtained from a database of 428 in-house usnic acid derivatives through pharmacophore filtering steps. Subsequent docking simulation on DENV-3 NS-5 RdRp afforded 41 compounds with a strong binding affinity towards the enzyme. The pharmacokinetics and drug likeness prediction resulted in seven hit compounds, which eventually undergo cytochrome P450 enzyme screening to obtain the lead compound, labelled as 362. In addition, molecular dynamic (MD) simulation of lead compound 362 was performed to verify the stability of the docked complex and the binding posture acquired in docking experiments. Overall, the lead compounds have shown a high fit value of pharmacophore, strong binding affinity towards RdRp enzyme, good pharmacokinetics, and drug likeness properties. The discovery of a new usnic acid derivative as a novel anti-DENV agent targeting RdRp could lead to further drug development and optimization to treat dengue.