Diterpenes/Diterpenoids and Their Derivatives as Potential Bioactive Leads against Dengue Virus: A Computational and Network Pharmacology Study

Abstract

Dengue fever is a dangerous infectious endemic disease that affects over 100 nations worldwide, from Africa to the Western Pacific, and is caused by the dengue virus, which is transmitted to humans by an insect bite of Aedes aegypti. Millions of citizens have died as a result of dengue fever and dengue hemorrhagic fever across the globe. Envelope (E), serine protease (NS3), RNA-directed RNA polymerase (NS5), and non-structural protein 1 (NS1) are mostly required for cell proliferation and survival. Some of the diterpenoids and their derivatives produced by nature possess anti-dengue viral properties. The goal of the computational study was to scrutinize the effectiveness of diterpenoids and their derivatives against dengue viral proteins through in silico study. Methods: molecular docking was performed to analyze the binding affinity of compounds against four viral proteins: the envelope (E) protein, the NS1 protein, the NS3 protein, and the NS5 protein. Results: among the selected drug candidates, triptolide, stevioside, alepterolic acid, sphaeropsidin A, methyl dodovisate A, andrographolide, caesalacetal, and pyrimethamine have demonstrated moderate to good binding affinities (−8.0 to −9.4 kcal/mol) toward the selected proteins: E protein, NS3, NS5, and NS1 whereas pyrimethamine exerts −7.5, −6.3, −7.8, and −6.6 kcal/mol with viral proteins, respectively. Interestingly, the binding affinities of these lead compounds were better than those of an FDA-approved anti-viral medication (pyrimethamine), which is underused in dengue fever. Conclusion: we can conclude that diterpenoids can be considered as a possible anti-dengue medication option. However, in vivo investigation is recommended to back up the conclusions of this study.

Investigating the Anticancer Potential of Salvicine as a Modulator of Topoisomerase II and ROS Signaling Cascade

“…Salvicine, in addition to inducing genomic DNA damage, has been demonstrated to cause telomere erosion and to decrease the functioning of the telomerase enzyme ( 39 , 49 ). The trf2 gene encodes the TRF2 (telomere repeat binding factor 2) protein, which is a major telomerase and plays a critical role in telomere maintenance with DDR ( 51 , 153 ). Such noble compound is directly involved in blocking the overexpressed TRF2 protein via transcription and proteasome degradation, eventually downregulating cellular proliferation and halting cancer progression.…”

Structure-based computational approaches for characterization and functional elucidation of the fusion protein from Nipah henipavirus

“…The alpha-carbon unit of all amino acids, except for glycine, is asymmetric, indicating that it is connected to four distinct chemical constituents (atoms or atom pairs) [29,30]. Consequently, amino acids, except glycine, can appear in two distinct spatial or geometric configurations (i.e., isomers), which resemble left and right hands [31][32][33]. ExPASy ProtParam tool identified the physicochemical characteristics of the protein, such as amino acid compositions, atomic composition, and protein half-life calculation (Figure 1).…”

A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells

“…The discovery or development of chemicals that can kill malformed or cancer cells, without being toxic or harming their healthy counterparts, is of utmost significance, and has attracted the attention of scientists all over the world [ 16 , 17 , 18 , 19 ]. Some plant-derived substances or phytochemicals have been found to be highly effective anticancer therapies in recent years, in addition also beneficial against a variety of other disorders [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”