A potent virucidal activity of functionalized TiO2 nanoparticles adsorbed with flavonoids against SARS-CoV-2.

The coronavirus SARS-CoV-2 has caused a pandemic with > 550 millions of cases and > 6 millions of deaths worldwide. Medical management of COVID-19 relies on supportive care as no specific targeted therapies are available yet. Given its devastating effects on the economy and mental health, it is imperative to develop novel antivirals. An ideal candidate will be an agent that blocks the early events of viral attachment and cell entry, thereby preventing viral infection and spread. This work reports functionalized titanium dioxide (TiO2)-based nanoparticles adsorbed with flavonoids that block SARS-CoV-2 entry and fusion. Using molecular docking analysis, two flavonoids were chosen for their specific binding to critical regions of the SARS-CoV-2 spike glycoprotein that interacts with the host cell angiotensin-converting enzyme-2 (ACE-2) receptor. These flavonoids were adsorbed onto TiO2 functionalized nanoparticles (FTNP). This new nanoparticulate compound was assayed in vitro against two different coronaviruses; HCoV 229E and SARS-CoV-2, in both cases a clear antiviral effect was observed. Furthermore, using a reporter-based cell culture model, a potent antiviral activity is demonstrated. The adsorption of flavonoids to functionalized TiO2 nanoparticles induces a ~ threefold increase of that activity. These studies also indicate that FTNP interferes with the SARS-CoV-2 spike, impairing the cell fusion mechanism. KEY POINTS/HIGHLIGHTS: • Unique TiO2 nanoparticles displaying flavonoid showed potent anti-SARS-CoV-2 activity. • The nanoparticles precisely targeting SARS-CoV-2 were quantitatively verified by cell infectivity in vitro. • Flavonoids on nanoparticles impair the interactions between the spike glycoprotein and ACE-2 receptor.

An insight into anti-biofilm and anti-quorum sensing activities of the selected anthocyanidins: the case study of Pseudomonas aeruginosa PAO1.

Anti-biofilm activity of three anthocyanidins (pelargonidin, cyanidin and delphinidin) was evaluated for the first time at in vitro conditions. All the compounds reduced the formation of Pseudomonas aeruginosa PAO1 biofilm at low sub-MIC (0.125 MIC) with delphinidin (c 56.25 µg/mL) being the most active (43%). In comparison, ampicillin (c 93.75 µg/mL) and streptomycin (c 21.25 µg/mL) (used as positive controls) were considerably less effective at the same sub-MIC (8 and 12%, respectively). Furthermore, at 0.5 MIC (c 225 µg/mL) this anthocyanidin molecule partly reduced the bacterial protrusions. However, no any of the aforementioned compounds inhibited the production of pyocyanin by the bacterial strain P. aeruginosa PAO1. Taken all together, the delphinidin scaffold could be taken into consideration for the design of the novel and more effective anti-biofilm agents inspired by the anthocyanidins.