Silver nanoparticles capped with Sutherlandia frutescens exhibited potent anti-HIV activity, immunomodulatory effect, and non-cytotoxicity in different human cell lines

Abstract

Antiretroviral therapy (ART) has reduced the burden of HIV-1, however, cytotoxicity and drug resistance remain significant challenges. Investigating Sutherlandia frutescens' bioactive compounds capped with silver nanoparticles offers potential new therapeutic avenues against HIV-1. In this study, we synthesized, characterized, and evaluated the cytotoxicity, anti-HIV activity, and immunomodulatory effects of green-synthesized silver nanoparticles capped with Sutherlandia frutescens (SF-AgNPs) on various cell lines. SF-AgNPs were synthesized using aqueous extracts of S. frutescens and characterized by UV–Vis, FTIR, SEM, TEM, XRD, and EDX analyses. Cytotoxicity was assessed by MTT assay in astrocytes, HepG2, 293 T, and TZM-bl cell lines. Antiviral activity was measured using a luciferase-based assay in HIV-1-infected TZM-bl cells and a time-of-addition assay. Immunomodulatory effects on CD4+ and CD8+ T cells were determined via flow cytometry. SF-AgNPs were predominantly spherical (average 24 nm), stable, and capped with plant polyphenols. They showed low cytotoxicity with CC₅₀ values above 100 μg/mL in most cell lines, except astrocytes. SF-AgNPs exhibited strong anti-HIV-1 activity (IC₅₀: 0.2142 μg/mL; SI: 816.67) and inhibited HIV-1 at the viral attachment and reverse transcription stages, outperforming the plant extract and silver nanoparticles alone. They also selectively reduced CD4+ T cell activation without affecting CD8+ T cells. This study demonstrates that SF-AgNPs are non-toxic, potent inhibitors of HIV-1 in different stages of HIV-1 infection, and modulate immune activation. These findings support their potential as a novel adjunct therapy in HIV management, combining traditional medicine and nanotechnology.