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Antibacterial treatment has grown difficult due to the increasing growth in bacterial infections, as well as their tolerance to most first-line antibiotics. This is a severe danger to the world’s human health in the 21st century, necessitating further research to identify drugs with improved antibacterial effects and broad-spectrum functions. This study aimed to discover anti-bacterial agents through the molecular docking and in silico approach. Most responsive thirty (32) compounds on UPLC-Q-TOF/MS analysis were selected from our previous report to get the hit compound(s) against inhibition of cell wall synthesis, inhibition of protein synthesis, interference with nucleic acid synthesis, inhibition of a metabolic pathway, inhibition of membrane function and inhibition of adenosine triphosphate (ATP) synthase. From the molecular docking results, we afforded six compounds for cell wall synthesis protein, four compounds for protein synthesis protein, five for nucleic acid synthesis protein, three for metabolic pathway protein, four for membrane function protein and three for ATP synthase protein which eventually undergoes the pharmacokinetic and drug-likeness properties to obtain lead compound(s). Finally, we discovered that compounds Turpinionosides B, Polydatin, Ledebouriellol, and Pterodontoside A have the strongest binding interactions with cell wall synthesis, inhibition of protein synthesis and inhibition of metabolic pathway synthesis, interference with nucleic acid synthesis and inhibition of ATP synthase, inhibition of membrane function proteins, respectively. These compounds have the potential to become an anti-bacterial therapeutic candidate due to their promising pharmacological properties.

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.