UNIVERSIDADE ESTADUAL PAULISTA

“JÚLIO DE MESQUITA FILHO”

Instituto de Ciência e Tecnologia

Campus de São José dos Campos

LITERATURE REVIEW DOI: https://doi.org/10.4322/bds.2023.e3721

Braz Dent Sci 2023 Apr/Jun;26 (2): e3721

Silver nanoparticles in mouthwashes against infection caused by

SARS-CoV-2: a scoping review

Nanopartículas de prata em enxaguatórios bucais para uso em infecções por SARS-CoV-2: uma revisão de escopo

Kelly Fernanda MOLENA

, Camila Raíssa Oliveira Gontijo MARTINS

, Carolina Alves Freiria de OLIVEIRA

,

Murilo Fernando Neuppmann FERES

, Alexandra Mussolino de QUEIROZ



1 - Pós Graduanda do Programa de Odontopediatria, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão

Preto, SP, Brasil

2 - Pós Graduanda do Programa de Reabilitação Oral Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão

Preto, SP, Brasil.

3 - Departamento de Clínica Infantil, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil

How to cite: Molena KF, Martins CROG, Oliveira CAF, Feres MFN, Queiroz AM. Silver nanoparticles in mouthwashes against infection

caused by SARS-CoV-2: a scoping review. Braz Dent Sci. 2023;26(2):e3721. https://doi.org/10.4322/bds.2023.e3721

ABSTRACT

The Silver nanoparticle (AgNPs) have received attention for their antiviral potential against SARS-CoV-2. The

objective is to conduct a scope review and map the scientic evidence on the use of AgNPs in mouthwashes as

an adjunct in decreasing the viral load in the oral cavity of patients with SARS-CoV-2. A search was performed

in the PubMed, Medline, Scielo databases, and a manual search in the reference lists, following the standards

of the Joanna Briggs Institute for Scoping Review without restriction of year, language or sample size. Thus,

14 articles were included, where they researched the use of AgNPs with antiviral effect against SARS-CoV-2,

mouthwashes for SARS-CoV-2 and AgNPs as mouthwashes. We can suggest that AgNPs are likely antiviral

therapies for SARS-CoV-2 and its use in mouthwashes associated with other therapies are promising strands for

decreasing viral load and infection by the virus.

KEYWORDS

Nanoparticles; Silver; Mouthwashes; COVID-19; SARS-CoV-2.

RESUMO

As nanopartículas de prata (AgNPs) têm recebido atenção por seu potencial antiviral no SARS-CoV-2. O objetivo

deste trabalho é realizar uma revisão de escopo e mapear as evidências cientícas sobre o uso de AgNPs em

bochechos como adjuvante na diminuição da carga viral na cavidade oral de pacientes com SARS-CoV-2. Foi

realizada busca nas bases de dados PubMed, Medline, Scielo e busca manual nas listas de referências, seguindo

os padrões do Joanna Briggs Institute for Scoping Review sem restrição de ano, idioma ou tamanho da amostra.

Assim, foram incluídos 14 artigos, onde pesquisaram o uso de AgNPs com efeito antiviral contra SARS-CoV-2,

enxaguatórios bucais para SARS-CoV-2 e AgNPs como enxaguatórios bucais, vertentes promissoras para diminuição

da carga viral e infecção pelo vírus.

PALAVRAS-CHAVE

Nanopartículas; Prata; Enxaguatórios bucais; COVID-19; SARS-CoV-2.

Braz Dent Sci 2023 Apr/Jun;26 (2): e3721

Molena KF et al.

Silver nanoparticles in mouthw ashes against infection caused by SARS-CoV -2: a scoping review

Molena KF et al.

Silver nanoparticles in mouthwashes against infection caused

by SARS-CoV-2: a scoping review

Abbreviations

Silver nanoparticles (AgNPs), Severe acute

respiratory syndrome (Sars-CoV-2), Center

for Disease control and prevention (CDC),

Respiratory syncytial virus (RSV), Hepatitis B

virus (HBV), Human immunodeficiency virus

(HIV), PRISMA (Preferred Report on Systematic

Reviews and Meta-Analysis), Angiotensin-

converting enzyme receptor 2 (ACE2)

INTRODUCTION

At the end of 2019, a virus emerged in

Wuhan, China, which would later be called

severe acute respiratory syndrome coronavirus 2,

and spread rapidly around the world causing

a global health emergency [1]. According to

the Centers for Disease Control and Prevention

(CDC) in the United States [2], the transmission

of the virus is carried out mainly through direct

contact or respiratory droplets [3] in a close

and time-dependent manner, in addition to air

transmission in certain circumstances, as most

recently demonstrated [4,5], including prolonged

exposure in an enclosed space without proper

air handling [6,7,8]. Despite advances, the

complexity of transmission and presentation

of the disease has increased this, added to

new variants brings the need to develop new

preventive approaches [9].

The oral cavity is an important reservoir of

SARS-CoV-2 [10,11,12], the use of an antiviral

mouthwash is an interesting strategy, especially

in the initial stage of the disease [13], where

its viral load is extremely high in saliva [7,14].

In addition, saliva is an important source of

transmission during the COVID-19 pandemic [10].

When a person coughs, sneezes, breathes or talks,

drops of saliva are produced and can dissipate the

virus [10,15]. Considering mouthwash as agents

that can reduce the viral load of SARS-CoV-2 in

the ght against the COVID-19 [10,16] pandemic

is an extremely important concept to be taken

into account [10,17].

In this way, nanomaterials can be described

as single structures [18], free or in a compound,

with a size within the nanometer range, generally

less than 100 nm in at least one of its three

dimensions [18,19]. There is a growing interest

in nanomaterials, precisely because of their new

or improved physico-chemical properties, such as

durability, chemical reactivity, biocompatibility,

conductivity or reduced toxicity [18,20]. Thus,

they can be used in disinfectants, diagnostics,

imaging tools, dressings, clothing, anti-cancer

therapies, pharmaceuticals, drug administration,

vaccines, diagnostic techniques and implants,

among others [21,22,23]. Also, development

of antiviral and antimicrobial drugs [24,25].

Antiviral nanomaterials are typically smaller

than most viral particles, such as the SARS-

CoV-2 viral particle, which has an average size

of 120 nm [19,26], so they can interact with the

entire viral particle or with surface proteins and

other components structural, leading to virus

inactivation [10].

Silver is an elemental metal and has a broad

spectrum antimicrobial action against bacteria,

fungi and viruses [27]. Silver nanoparticles

(AgNPs) are highly versatile and are already

present in microbicides for biological surfaces

in various forms, such as medical devices,

wound dressings, sprays and tissues [28].

In dentistry, AgNPs have drawn special attention

because of their broad spectrum of antimicrobial

activity, where their efcacy has already been

demonstrated, however, the toxicity of AgNPs for

use in oral infections is still being discussed [29].

AgNPs also attract the attention of dental

researchers due to their potential for anticarious

use [30], as they can inhibit the growth and

adhesion of cariogenic bacteria especially

Streptococcus mutans

[30,31,32]. Studies

investigate the addition of AgNPs in adhesives,

toothpaste and restorative materials, studying

the association between AgNPs and uoride to

stop caries, potentiating an antibacterial and

remineralizing agent [33,34]. In addition, studies

have demonstrated the potent antiviral action

of AgNPs against various human pathogenic

viruses, such as respiratory syncytial virus (RSV),

influenza virus, norovirus, hepatitis B virus

(HBV), human immunodeciency virus (HIV)

[26,35,36], and more currently, as a possibility

for SARS-CoV-2 [28,35,36].

Recent studies have demonstrated the

effectiveness of different mouthwashes to

reduce salivary load and consequently to help

reduce the transmission of SARS-CoV-2 [37,38].

However, there are still no studies in the literature

evaluating the effectiveness of mouthwashes with

AgNPs in reducing salivary viral load in patients

with COVID-19 [39].

Braz Dent Sci 2023 Apr/Jun;26 (2): e3721

Molena KF et al.

Silver nanoparticles in mouthw ashes against infection caused by SARS-CoV -2: a scoping review

Molena KF et al.

Silver nanoparticles in mouthwashes against infection caused

by SARS-CoV-2: a scoping review

Therefore, the objective of this scope review

is to map the scientic evidence and any gaps in

knowledge about the use of mouthrinses with

AgNPs as a potent antiviral agent or adjunct in

decreasing the viral load in the oral cavity of

patients infected with SARS-CoV-2.

MATERIAL AND METHODS

The methodology was dened following the

Joanna Briggs Institute for Scoping reviews [40]

and the PRISMA-ScR guidelines (Preferred

Report on Systematic Reviews and Meta-

Analysis for Scoping Reviews – Figure 1) [41].

The bibliographic research was conducted in

3 databases and in the gray literature, whose

question was to map evidence on the use of

AgNPs as an antiviral agent against SARS-CoV-2,

and its use in mouthwashes with the potential to

reduce viral load in the oral cavity, from patients

affected by SARS-CoV-2, and with the guiding

question: Mouthwashes with AgNPs, can be

effective in reducing the viral load in oral cavity,

of patients affected by SARS-CoV-2?

Scope of the search

A search was performed in the PubMed,

Medline, Scielo databases, as well as a manual

search in the reference lists of the studies

that were included [42], without restriction

of year, language or sample size. The first

phase established an investigation to define

the terms MeSH (Medical Subject Headings) to

ensure high sensitivity and accuracy, and the

researchers tracked titles and publications of

abstracts. The MeSH terms used in searches in

all databases were “COVID-19” or “SARS-CoV-2”

or “Coronavirus Infections” or “Coronavirus” and

“Mouthwashes” or “Mouth-rinses” and “Silver

nanoparticles” and “Antiviral”, and crossed

elements (“silver nanoparticle” and “oral rinses”),

(“silver nanoparticles”and “COVID-19”), (“silver

nanoparticle”and COVID-19 and mouthwashe)

and (“oral rinse” and “ COVID-19”).

Inclusion and exclusion criteria

This review included studies reporting the

use of AgNPs in mouthwashes, as a therapeutic

approach to reduce viral load in patients infected

with SARS-CoV-2, to solve the hypothesis that

it would be possible to use mouthwashes with

AgNPs to reduce viral load in patients infected

with SARS-CoV-2. At rst, the original articles,

without language or year restriction, with

an abstract available in the database, were

evaluated and validated within the inclusion

criteria, by reading the title and abstract, by two

authors [43]. Inclusion criteria were defined

Figure 1 - PRISMA diagram. Process of identiﬁcation and inclusion of studies - Preferred Reporting Items for Systematic Reviews and Meta-

Analyzes (PRISMA) diagram ﬂow.

Braz Dent Sci 2023 Apr/Jun;26 (2): e3721

Molena KF et al.

Silver nanoparticles in mouthw ashes against infection caused by SARS-CoV -2: a scoping review

Molena KF et al.

Silver nanoparticles in mouthwashes against infection caused

by SARS-CoV-2: a scoping review

using the PCC strategy (Population, Concept,

Context - Table I) and consisted of primary

research studies in full, “in vivo”, “in vitro” or

animal research, and excluded opinion articles,

letters to editor and literature reviews.

Selection and quality assessment of relevant

studies

The articles selected according to the

election criteria were retrieved in PDF format,

numbered and randomly distributed among two

researchers [43]. To increase the sensitivity and

quality of review, the references list was manually

checked. To discuss divergences, a consensus

meeting was held [43] and an third experienced

researcher was consulted

Extraction and processing

The articles included in the study were

randomly distributed among the researchers for

the collection of relevant data [43]. The articles

were then organized into 03 tables, namely:

studies that portray the use of AgNPs against

SARS-CoV-2 with antiviral potential (Table II);

studies that portray the use of mouthwashes for

patients with COVID-19 (Table III) and studies

that bring AgNPs in mouthwashes (Table IV).

RESULTS

After the process of evaluation and selection

of articles, 14 articles were included in the scoping

review, 03 of which portray AgNPs as antiviral

Table I - PCC estrategy and the criteria included in the search for articles

PCC Estrategy

Population People infected by SARS-CoV-2

Concept Administration of mouthwashes with AgNPs to control / reduce the viral load of SARS-CoV-2

Context

Global health, in view of the current SARS-CoV-2 pandemic, and its high infectivity, mainly via the oral cavity

through the formation of aerosol in the dental oﬃce, as well as droplets produced in speaking, coughing, and

sneezing, for example.

Table II - Studies that portray the use of AgNPs with antiviral potential for SARS-CoV-2

Autor and Year Title Estrategy of use AgNPs Outcomes

Changetal., 2021 [44]

Nanoparticle composite TPNT1

is eﬀective against SARS-CoV-2

and inﬂuenza viruses

A composite of metal

nanoparticles, namely TPNT1,

containing Au-NP (1 ppm),

Ag-NP (5 ppm), ZnO-NP (60

ppm) and ClO 2 (42.5 ppm)

in aqueous solution was

prepared and characterized

by spectroscopy, transmission

electron microscopy, dynamic

light scattering analysis and

potentiometric titration

TPNT1 inhibited six major

subtypes of SARS-CoV-2, and

interfered with the formation

of syncytium. It also eﬀectively

reduced the cytopathic eﬀects

induced by human (H1N1) and

avian (H5N1) viruses, including

those isolated from wild-type

and resistant to oseltamivir

viruses.

Jeremiahetal., 2020 [28]

Potent antiviral eﬀect of silver

nanoparticles on SARS-CoV-2.

PVP-AgNP 10 in stock

concentration of 20 ppm and

cAg were obtained from Sigma.

AgNPs of diﬀerent sizes;

AgNP 2 (Cat No: US7150),

AgNP 15 (Cat No: US7091),

AgNP 50, AgNP 80 and AgNP

100 (US1038W), all silver

formulations were dispersed

in water and the desired

concentration was prepared by

diluting in sterile distilled water.

Particles in diameter around

10 nm were eﬀective in

extracellular inhibition of SARS-

CoV-2 at concentrations ranging

from 1 to 10 ppm, while the

cytotoxic eﬀect was observed

at concentrations of 20 ppm

and above. The luciferase-

based pseudovirus entry assay

revealed that AgNPs potently

inhibited the viral entry step by

disrupting viral integrity.

Valdez-Salasetal., 2021 [45]

Promotion of Surgical Masks

Antimicrobial Activity by

Disinfection and Impregnation

with Disinfectant Silver

Nanoparticles.

Developed a new alcohol

disinfectant formulation

combining special surfactants

and AgNPs

The nano-disinfectant provides

a valuable strategy for

eﬀective decontamination,

reuse and even promotion

of antimicrobials for surgical

masks for frontline clinical

personnel.

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Molena KF et al.

Silver nanoparticles in mouthw ashes against infection caused by SARS-CoV -2: a scoping review

Molena KF et al.

Silver nanoparticles in mouthwashes against infection caused

by SARS-CoV-2: a scoping review

Table III - Studies that portray the use of mouthwashes in SARS-CoV-2 virus

Author and Year Title

Mouthwashes studied

against SARS-CoV-2

Outcome

Seneviratneetal., 2021 [37]

Eﬃcacy of commercial

mouth-rinses on SARS-

CoV-2 viral load in saliva:

randomized control trial.

Iodine-povidone (PVPI)

0.5%, chlorhexidine 0.2%,

cetylpyridine chloride (CPC)

0.075%

The use of CPC and PI formulated that

commercial mouthwashes can be useful as

a pre-procedure rinse to help reduce the

transmission of SARS-CoV-2.

Steinhaueretal., 2021 [43]

Comparison of the

vitro

eﬃcacy of diﬀerent

mouthwash solutions

targeting SARS-CoV-2 based

on the European Standard

EN 14476.

Chlorhexidine digluconate

0.2% and octenidine

dihydrochloride (OCT)

Based on these

in vitro

data, the OCT

rinse is an interesting candidate for future

clinical studies to prove its eﬀectiveness in

a potential prevention of the transmission

of SARS-CoV-2 by aerosols.

Xuetal., 2020 [46]

Diﬀerential eﬀects of

antiseptic mouth rinses on

SARS-CoV-2 infectivity

vitro

Essential oils with ethanol

(20-30% Ethanol Thymol

0.064% Methyl salicylate

0.06% Menthol (Racementol)

0.042% 0.092% Eucalyptol);

1% povidone-iodine;

Hydrogen peroxide 1.5%

and chlorhexidine gluconate

0.12%

All mouthwashes tested against inactivated

SARS-CoV-2 virus. Listerine and CHG were

less cytotoxic than Colgate Peroxyl or

povidone-iodine and were active against

the virus. When mouthwash was present in

the cell culture during infection, the potent

antiviral eﬀect of mouthwash was in part

due to the cytotoxicity associated with

mouthwash.

Pelletieretal., 2021 [47]

Eﬃcacy of Povidone-Iodine

Nasal and Oral Antiseptic

Preparations against SARS-

CoV-2

PVPI 1% to 5%

The nasal and oral antiseptic solutions of

PVPI are eﬀective in inactivating SARS-

CoV-2 in a variety of concentrations (nasal,

oral and surface decontamination) after

exposure times of 60 seconds.

Bidraetal., 2020 [48]

Rapid

in vitro

inactivation of

SARS-CoV-2 using povidone-

iodine oral antiseptic rinse

(PVPI).

PVPI 0,5%, 1% and 1,5%

PVPI preparations rapidly inactivated the

SARS-CoV-2

in vitro

. The virucidal activity

was present at the lowest concentration of

0.5% PVPI and the lowest contact time of

15 seconds.

Bidraetal., 2020 [49]

Comparison of

in vitro

inactivation of SARS-CoV-2

with hydrogen peroxide

and povidone-iodine oral

antiseptic rinses (PVPI).

PVPI 0.5%, 1.25% and 1.5%,

and hydrogen peroxide

(H2O2) was tested at 3%

and 1.5%

SARS-CoV-2 was completely inactivated

by the oral antiseptic rinse of PVPI

vitro

, in the lowest concentration of 0.5%

and in the shortest contact time of 15

seconds. H2O2 at the recommended oral

rinse concentrations of 1.5% and 3.0% was

minimally eﬀective as a virucidal agent

after contact times of up to 30 seconds.

Therefore, the pre-procedure rinse with

PVPI diluted in the range of 0.5% to 1.5%

may be preferable to hydrogen peroxide

during the COVID-19 pandemic.

Gottsauneretal., 2020 [50]

A prospective clinical

pilot study on the eﬀects

of a hydrogen peroxide

mouthrinse on the intraoral

viral load of SARS-CoV-2.

Hydrogen peroxide 1%

A 1% hydrogen peroxide mouthwash

does not reduce the intraoral viral load

in individuals positive for SARS-CoV-2.

However, the culture of the virus gave no

indication of the eﬀects of the mouthwash

on the infectivity of the detected RNA

copies.

Koch-Heieretal., 2021[51]

Inactivation of SARS-CoV-2

through treatment with the

mouth rinsing Solutions

ViruProX® and BacterX® Pro.

Microorganisms.

ViruProX® with 0.05%

cetilpiridinium (CPC)

and 1.5% hydrogen

peroxide (H2O2); BacterX®

pro containing 0.1%

chlorhexidine (CHX), 0.05%

CPC and 0.005% sodium

ﬂuoride (F-); and some of

their individual components

as 0.05% CPC solution, 0.1%

CHX solution, a combination

of 0.05% CPC with 0.1%

CHX solution, and 1.5%

H2O2 solution

While a combination of CPC and CHX,

as well as CPC alone led to a signiﬁcant

reduction in infectious viral particles, H2O2

and CHX alone had no virucidal eﬀect

against SARS-CoV-2. It can be assumed

that pre-procedure mouth rinsing with

ViruProX ® or BacterX ® pro will reduce

the viral load in the oral cavity and, thus,

decrease the transmission of SARS-CoV-2 in

dental practice.

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Silver nanoparticles in mouthw ashes against infection caused by SARS-CoV -2: a scoping review

Molena KF et al.

Silver nanoparticles in mouthwashes against infection caused

by SARS-CoV-2: a scoping review

agents (Table II), 08 articles bring the use of

mouthwashes against SARS-CoV- 2 (Table III)

and finally, 03 articles expose AgNPs in

mouthwashes (Table IV). These were articles

in the English language, published between

2014 and 2021, covering experimental studies

“in vitro” and “in vivo”.

DISCUSSION

The SARS-CoV-2 has already caused millions

of deaths worldwide and due to its rapid spread it

is difcult to contain the transmission [9]. Person-

to-person contact through respiratory droplets

generated by sneezing and coughing in infected

individuals has been shown to be the main route

of transmission of SARS-CoV-2 [10,43,44,46].

In addition to the efficient use of personal

protective equipment, such as masks, and

maintaining social distance, it is necessary to

implement more active prevention strategies.

One of the main approaches to minimize the

risk [37] of transmission of SARS-CoV-2 would

be to reduce the viral load of SARS-CoV-2 in

the saliva of infected patients [37], which is

particularly important in high-risk procedures,

such as dental treatment [37,47]. When a

symptomatic or asymptomatic patient goes to

the dental office, he can transmit the SARS-

CoV-2 through contact with other people,

direct transmission to the dentist or indirect

transmission through contamination of surfaces,

even more so today with the exibility in use of

masks [55].

The use of antiseptic mouthwash has been

suggested as a pre-procedural infection control

measure by health authorities since the early

stage of the COVID-19 pandemic [37], when

they recommended the use of mouthwashes with

povidone-iodine (PVP-I) [47,48,49], hydrogen

peroxide [49,50] or cetylpyridinium chloride

(CPC) [43,46] as a pre-procedure preventive

measure. However, it is important to emphasize

that these recommendations were not based in

robust scientic evidence. The rst case report on

the effectiveness of mouthwashes in reducing the

viral load of SARS-CoV-2 in saliva was reported

in Korea [13,37,56]. Other studies suggested that

mouthwash with PVP-I could reduce the SARS-

CoV-2 salivary viral load [47,48,49], and the

efcacy of virucidal mouthwash activity against

SARS-CoV-2 [46,51].

Silver nanoparticles are antiviral

agents against several types of

viruses [44,48,49,52,57,58,59,60,61,62,63], in

addition to the antimicrobial activity against Gram-

Table IV - Studies that portray AgNPs in mouthwashes

Author and Year Title

Strategy for the use of AgNPs

in mouthwashes

Outcome

Luetal., 2018 [52]

Redox/pH dual-controlled release

of chlorhexidine and silver ions

from biodegradable mesoporous

silica nanoparticles against oral

bioﬁlms.

They manufactured biodegradable

disulﬁde bridge (MSNs)

mesoporous silica nanoparticles

to co-deliver AgNPs and CHX

(chlorhexidine) for bioﬁlm

inhibition, (Ag-MSNs @ CHX).

Ag-MSNs @ CHX exhibited dose-

dependent antibacterial activity

against planktonic formation and

Streptococcus mutans

clones, and

had an increased, long-term ability

to restrict the growth of S. mutans

bioﬁlms compared to free CHX,

and was less toxic to oral cells,

even

in vivo

Ahrarietal., 2015 [53]

The antimicrobial sensitivity

Streptococcus mutans

and

Streptococcus sanguis

to colloidal

solutions of diﬀerent nanoparticles

applied as mouthwashes.

Was evaluated the antibacterial

eﬀects of colloidal solutions

containing zinc oxide, copper

oxide, titanium dioxide and silver

nanoparticles in

Streptococcus

mutans

and

Streptococcus sanguis

and compared the results with

those of chlorhexidine and sodium

ﬂuoride mouthwashes.

The antibacterial eﬀect of silver

nanoparticles was not desirable

against

Streptococcus mutans

Besinisetal., 2014 [54]

The antibacterial eﬀects of silver,

titanium dioxide and silica dioxide

nanoparticles compared to the

dental disinfectant chlorhexidine

Streptococcus mutans

using a

suite of bioassays.

This study investigated the

toxicity of silver (Ag), titanium

dioxide and silica nanoparticles

(NPs) against the oral pathogenic

species of

Streptococcus

mutans

, compared to the routine

disinfectant, chlorhexidine

AgNPs were the best disinfectants

and performed better than

chlorhexidine

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Silver nanoparticles in mouthw ashes against infection caused by SARS-CoV -2: a scoping review

Molena KF et al.

Silver nanoparticles in mouthwashes against infection caused

by SARS-CoV-2: a scoping review

positive and Gram-negative bacteria [53,54].

A possible antimicrobial mechanism of AgNPs

is attributable to suppression of respiratory

enzymes and interference in DNA functions by

released Ag

ions [44,52].

Elechiguerra et al. (2005) [57] in their study

showed that silver nanoparticles undergo size-

dependent interaction with HIV-1 and that they

inhibit virus infectivity in vitro. El-Mohamady et al.

(2018) [60] studied the inhibitory effect of silver

nanoparticles on bovine herpesvirus-1 and

showed that in non-toxic concentrations, AgNPs

were able to inhibit BoHV-1 when administered

before viral infection. Several other studies

in the literature report the effectiveness of

AgNPs as a potent antiviral against in humans

and animals diseases, such as HIV [57,58,59],

influenza [27,44], herpes type 1 and type

2 [60], respiratory syncytial virus, norovirus and

hepatitis B [27,28].

Since the effectiveness of silver nanoparticles

is known to be a potent antiviral agent, it

is suggested that AgNPs may be effective in

combating the transmission of SARS-CoV-2.

In this sense, several studies are being developed

and aim to test whether the AgNPs are also

effective against SARS-CoV-2. In that way, AgNPs

would have an antiviral effect on SARS-CoV-2 by

disrupting disulde bonds in spike protein and

ACE2 receptors [28], inactivating the virus and

preventing its replication or decreasing viral load

in situ (Figure 2).

In their study, Jeremiah et al. (2020)

[28] assessed numerous silver nanoparticles

with varying sizes and concentrations. They

found that silver nanoparticles with a diameter

of approximately 10 nm were successful in

inhibiting the extracellular growth of SARS-

CoV-2 at concentrations ranging from 1 to

10 ppm, while concentrations of 20 ppm and

above showed cytotoxic effects. Furthermore,

the luciferase-based pseudo virus entry assay

indicated that AgNPs effectively impeded the viral

entry process by disrupting the virus’s integrity.

The shortage of personal protective

equipment and crucial medical supplies, such as

surgical masks, is a major worry amid the COVID-

19 outbreak [45]. The researchers aimed to create

a cost-effective and straightforward study to

enhance the antimicrobial capabilities of surgical

Figure 2 - Representation of the SARS-CoV-2 viral replication pathway. AgNP in mouthwashes would act on SARS-CoV-2 spike protein receptors

and ACE2 receptors breaking their disulﬁde bridgs and preventing their viral replication.

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Silver nanoparticles in mouthw ashes against infection caused by SARS-CoV -2: a scoping review

Molena KF et al.

Silver nanoparticles in mouthwashes against infection caused

by SARS-CoV-2: a scoping review

masks by incorporating AgNPs. Their ndings

showed a microbial reduction rate exceeding

99.999% against various microorganisms, and the

method of reusing surgical masks did not affect

the ltration effectiveness, indicating no harmful

alterations. This nano-disinfectant method offers a

benecial approach for efcient decontamination,

reuse, and promotion of antimicrobial properties

of surgical masks, particularly for frontline

clinical staff [45]. Chang et al. (2021) [44]

conducted a study where they combined AgNPs

with other metallic nanoparticles in a compound

called TPNT1. They used an in vitro cell assay to

demonstrate that the compound was effective

in inhibiting six signicant subtypes of SARS-

CoV-2 at concentrations suitable for use as

food additives. TPNT1 was observed to block

viral entry by preventing the binding of SARS-

CoV-2 spike proteins to ACE2 and disrupting

syncytium formation. Thus, this study suggests

that this composite of metallic nanoparticles

could serve as a prophylactic for preventing

SARS-CoV-2 infections. To decrease the risk of

transmission in patients with COVID-19, the viral

load in the oral cavity must be decreased. Several

studies have concluded that mouthwashes

containing cetylpyridinium chloride (CPC) or

povidone-iodine (PVP-I) can decrease the severity

of COVID-19, reducing the oral viral load of SARS-

CoV-2 and can decrease the risk of transmission

by reducing the load viral in droplets generated

in normal life or in aerosols produced during

dental procedures [64]. In addition, if we look

at mouthwashes that are marketed as containing

antiviral molecules, other compounds may be of

interest in the ght against SARS-CoV-2, such as

hydrogen peroxide, chlorhexidine, cyclodextrin,

Citrox, essential oils, among others [10,65].

The effectiveness of mouthwashes against SARS-

CoV-2 may support their use as additional hygiene

measures in patients with COVID-19 [47],

thereby reducing the viral load in ambulatory

and clinical environments [47], and their use may

be adjunctive to personal protective equipment

for dentists and healthcare professionals during

COVID-19 outbreaks [48,49,66]. A randomized

trial conducted by Santos et al. (2021) [67]

showed promising results where the use of

a mouthwash with an antiviral derivative of

phthalocyanine reduced symptoms, spread of

infection, and hospital stay period in patients

with COVID-19. This reinforces the importance

of conducting further studies in this area.

Our work aimed to map the current evidence

on the use of AgNPs in mouthwashes for patients

with COVID-19, the limitation of this study was

that we were unable to include in the review any

study where an AgNPs mouthwash was used for

SARS-CoV-2. But this hypothesis is supported

by the fact that the nanoparticle has antiviral

properties well described in the literature and

allows for a call for controlled clinical studies

on the topic of considerable importance. Given

this information and considering the various

studies on AgNPs and its antiviral potential, it is

suggested, with this scoping review, new studies

that associate AgNP with mouthwashes and in

this way it is possible to use this nanotechnology

appropriately as a way to help combat SARS-

CoV-2.

In conclusion, this study mapped the

evidence around the use of AgNPs as an antiviral

agent and the use of mouthwashes with potential

against SARS-CoV-2. With the ndings presented

in this study, we can suggest that mouthwashes

with AgNPs have the potential to act against

SARS-CoV-2, as a way of reducing viral load,

preventing viral multiplication, but studies need

to be done to prove the hypothesis.

Author’s Contributions

KFM: Conceptualization. MFNF:

Methodology. MFNF: Formal Analysis. KFM,

CROGM: Investigation. KFM, CROGM, CAFO:

Data Curation. KFM, CROGM, CAFO: Writing

– Original Draft Preparation. AMQ: Writing –

Review & Editing. KFM: Project Administration.

KFM: Funding Acquisition.

Conict of Interest

No conicts of interest declared concerning

the publication of this article.

Funding

The authors declare that no nancial support

was received.

Regulatory Statement

A regulatory statement is not applicable as

this is a scoping review article.

Braz Dent Sci 2023 Apr/Jun;26 (2): e3721

Molena KF et al.

Silver nanoparticles in mouthw ashes against infection caused by SARS-CoV -2: a scoping review

Molena KF et al.

Silver nanoparticles in mouthwashes against infection caused

by SARS-CoV-2: a scoping review

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Zangrando MSR,etal. Beneficial effects of a mouthwash containing

an antiviral phthalocyanine derivative on the length of hospital stay

for COVID-19: randomised trial. Sci Rep. 2021;11(1):19937. http://

dx.doi.org/10.1038/s41598-021-99013-5. PMid:34620904.

Kelly Fernanda Molena

(Corresponding address)

Pós Graduanda do Programa de Odontopediatria, Faculdade de Odontologia de

Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil

Email: kelly.molena@usp.br

Date submitted: 2022 Dec 02

Accept submission: 2023 Apr 17