Abstract :
Lantana camara contains a variety of bioactive compounds including alkaloids, flavonoids, phenolic acids, terpenoids, glycosides and essentially oils with known anti-HIV-1 activity. Because antiretroviral drug resistance hinders therapeutic success, novel drug candidates are urgently needed. This study integrates network pharmacology, molecular docking, and in vitro validation to investigate how Lantana camara phytochemicals inhibit HIV-1 replication.
Lantana camara phytochemicals from the IMPPAT database and HIV targets from Genecards were overlapped via Venny 2.1. Protein-protein interaction network (PPI) was built in STRING and optimized in Cytoscape v3.10.3. Functional pathways were mapped using Shinygo, followed by molecular docking using Auto dock Vina v 1.1.2. Experimentally, Lantana camara crude extracts were prepared via boiling methods and methanol and ethanol extraction/ maceration. Cytotoxicity (CC50) was evaluated via MTT assay in TZM-bls, while antiviral activity (IC50) of both Lantana camara crude extracts and the top docked compounds were validated in TZM-bl cells using luciferase -based assay to calculate the Selectivity Index (SI).
Seventeen compounds satisfied with the ADMET criteria. The PPI network 18 hub genes enriched in apoptotic, immunoregulatory (hsa5235) and PD-L1/PD-1 checkpoint (hsa05235), HIF-1 (hsa04066), and PI3K-Akt (hsa04151 signaling pathways. Lantanolic and lantoic acids exhibited the strongest binding affinities toward NFKB1, MAPK1, and PRKCA (docking scores up to -10.6 kcal/mol). In vitro, the extracts were non-toxic (CC50 > 281 ug/mL). Both crude extracts and isolated top compounds exhibited moderate, dose-dependent HIV-1 inhibition IC50 = 67.61 ug/mL; maximum inhibition of [63]%), yielding a favourable safety profile with an SI value of 4.16.
Conclusion: Lantana camara crude extracts, alongside its constituent lantoic and lantanolic acids, moderately inhibit HIV-1 replication without cytotoxicity by modulating host signalling cascades and the PD-L1/PD-1 axis. These findings establish these compounds as viable, low-toxicity scaffolds for future antiretroviral development.
Biography:
I (Ntokozo Ntanzi) am a master’s student pursuing a degree in Medical Sciences at the University of KwaZulu-Natal. I have acquired a good foundation in understanding human physiology and medical biochemistry from my previous bachelor’s degrees. I have developed a strong interest in virology. My current research focuses on characterization of bioactive compounds from Lantana camara that exhibit anti-HIV-1 activity combining in vitro and in silico approaches aiming to elucidate its anti-HIV activity. Outside of academics, I enjoy reading and listening to music. I aspire to pursue a career in becoming a medical scientist.
