High Amplification of the Antiviral Activity of Curcumin through Transformation into Carbon Quantum Dots

Abstract

It is demonstrated that carbon quantum dots derived from curcumin (Cur‐CQDs) through one‐step dry heating are effective antiviral agents against enterovirus 71 (EV71). The surface properties of Cur‐CQDs, as well as their antiviral activity, are highly dependent on the heating temperature during synthesis. The one‐step heating of curcumin at 180 °C preserves many of the moieties of polymeric curcumin on the surfaces of the as‐synthesized Cur‐CQDs, resulting in superior antiviral characteristics. It is proposed that curcumin undergoes a series of structural changes through dehydration, polymerization, and carbonization to form core–shell CQDs whose surfaces remain a pyrolytic curcumin‐like polymer, boosting the antiviral activity. The results reveal that curcumin possesses insignificant inhibitory activity against EV71 infection in RD cells [half‐maximal effective concentration (EC50) >200 µg mL−1] but exhibits high cytotoxicity toward RD cells (half‐maximal cytotoxic concentration (CC50) <13 µg mL−1). The EC50 (0.2 µg mL−1) and CC50 (452.2 µg mL−1) of Cur‐CQDs are >1000‐fold lower and >34‐fold higher, respectively, than those of curcumin, demonstrating their far superior antiviral capabilities and high biocompatibility. In vivo, intraperitoneal administration of Cur‐CQDs significantly decreases mortality and provides protection against virus‐induced hind‐limb paralysis in new‐born mice challenged with a lethal dose of EV71.

Antiviral Effects of Curcumin on Adenovirus Replication

“…However, many research groups have synthesized and evaluated curcumin derivatives that show enhanced bioavailability, stability, and/or anti-viral activity [ 30 , 34 , 51 ]. The use of nanoparticles and other formulations and carriers can enhance curcumin solubility and bioactivity [ 21 ], which can improve antiviral activity [ 52 , 53 , 54 ]. Such approaches may enhance efficacy of curcumin against HAdV.…”

Curcumin as an Antiviral Agent

“…Protein expression Enterovirus 71 [13] Conformation of viral/cellular surface proteins Viral attachment Zika virus Chikungunya virus Vesicular stomatitis virus [14][15][16] Human respiratory syncytial virus [17,18]…”

“…Lin et al evaluated several curcumin-derived carbon quantum dot (Cur-CQD) formulations against EV71 [13]. These quantum dot formulations improve curcumin's solubility in water, which may explain its increased antiviral activity [13].…”

“…Lin et al evaluated several curcumin-derived carbon quantum dot (Cur-CQD) formulations against EV71 [13]. These quantum dot formulations improve curcumin's solubility in water, which may explain its increased antiviral activity [13]. In human rhabdomyosarcoma (RD) cells, all Cur-CQD formulations had superior CC 50 and EC 50 scores compared to curcumin, with Cur-CQD-180 (named for the heat applied during synthesis, i.e., 180 • C) having the highest selectivity index (SI, <0.07 vs. 2261.0, respectively) inhibiting EV71-induced cytopathic effect (CPE) and virus recovery [13].…”

“…These quantum dot formulations improve curcumin's solubility in water, which may explain its increased antiviral activity [13]. In human rhabdomyosarcoma (RD) cells, all Cur-CQD formulations had superior CC 50 and EC 50 scores compared to curcumin, with Cur-CQD-180 (named for the heat applied during synthesis, i.e., 180 • C) having the highest selectivity index (SI, <0.07 vs. 2261.0, respectively) inhibiting EV71-induced cytopathic effect (CPE) and virus recovery [13]. Cur-CQD-180 lowered expression of several viral proteins when added post-infection, such as the structural protein VP1 and non-structural proteins 3CD pro and 3D pol , in a dose-dependent manner [13].…”