Natural photosensitizers potentiate the targeted antimicrobial photodynamic therapy as the Monkeypox virus entry inhibitors: An in silico approach

Abstract

BackgroundMonkeypox is a viral zoonotic disease that has emerged as a threat to public health. Currently, there is no treatment approved specifically targeting Monkeypox disease. Hence, it is essential to identify and develop therapeutic approaches to the Monkeypox virus. In the current in silico paper, we comprehensively involve using computer simulations and modeling to insights and predict hypotheses on the potential of natural photosensitizers-mediated targeted antimicrobial photodynamic therapy (aPDT) against D8L as a Monkeypox virus protein involved in viral cell entry. Materials and methodsIn the current study, computational techniques such as molecular docking were combined with in silico ADMET predictions to examine how Curcumin (Cur), Quercetin (Qct), and Riboflavin (Rib) as the natural photosensitizers bind to the D8L protein in Monkeypox virus, as well as to determine pharmacokinetic properties of these photosensitizers. ResultsThe three-dimensional structure of the D8L protein in the Monkeypox virus was constructed using homology modeling (PDB ID: 4E9O). According to the physicochemical properties and functional characterization, 4E9O was a stable protein with the nature of a hydrophilic structure. The docking studies employing a three-dimensional model of 4E9O with natural photosensitizers exhibited good binding affinity. D8L protein illustrated the best docking score (−7.6 kcal/mol) in relation to the Rib and displayed good docking scores in relation to the Cur (−7.0 kcal/mol) and Qct (−7.5 kcal/mol). ConclusionsThe findings revealed that all three photosensitizers were found to obey the criteria of Lipinski's rule of five and displayed drug-likeness. Moreover, all the tested photosensitizers were found to be non-hepatotoxic and non-cytotoxic. In summary, our investigation identified Cur, Qct, and Rib could efficiently interact with D8L protein with a strong binding affinity. It can be concluded that aPDT using these natural photosensitizers may be considered an adjuvant treatment against Monkeypox disease.