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 i...

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Published in:Applied microbiology and biotechnology 2022-09, Vol.106 (18), p.5987-6002
Main Authors: León-Gutiérrez, Gabriela, Elste, James Edward, Cabello-Gutiérrez, Carlos, Millán-Pacheco, Cesar, Martínez-Gómez, Mario H., Mejía-Alvarez, Rafael, Tiwari, Vaibhav, Mejía, Armando
Format: Article
Language:English
Subjects:
ACE2
Angiotensin
Angiotensin-converting enzyme 2
Antiviral activity
Antiviral agents
Biomedical and Life Sciences
Biotechnological Products and Process Engineering
Biotechnology
Cell culture
Cell fusion
Coronaviruses
COVID-19
Flavonoids
Glycoproteins
Infectivity
Life Sciences
Mental health
Microbial Genetics and Genomics
Microbiology
Molecular docking
Nanoparticles
Pandemics
Peptidyl-dipeptidase A
Receptors
Severe acute respiratory syndrome coronavirus 2
Spike glycoprotein
Titanium dioxide
Viral diseases
Virus attachment
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Summary: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 (TiO 2 )-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 TiO 2 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 TiO 2 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 TiO 2 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. Graphical abstract
ISSN:0175-7598
1432-0614
DOI:10.1007/s00253-022-12112-9