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Spike Glycoprotein Hemagglutinin-esterase dimer

Membrane protein Membrane

Nucleocapsid protein and RNA

Envelop protein

SARS-CoV2

Introduction The COVID-19 pandemic began in late 2019, causing widespread health concerns. COVID-19 (SARS COV-2) belongs to the corona virus family, which is a group of enveloped RNA viruses with spike protein in its membrane envelope. Other members of this family are SARS COV and MERS COV, which have spread in recent years. Researchers have shown that more than 80% of the COVID- 19 genome resembles that of the SARS CoV.

1: Vergara-Buenaventura A, Castro-Ruiz C. Use of mouthwashes against COVID-19 in dentistry. Br J Oral Maxillofac Surg. 2020 Oct;58(8):924-927. doi: 10.1016/j.bjoms.2020.08.016. Epub 2020 Aug 15. PMID: 32859459; PMCID: PMC7428696.

2: Kelly N, Nic Íomhair A, McKenna G. Can oral rinses play a role in preventing transmission of Covid 19 infection? Evid Based Dent. 2020 Jun;21(2):42-43. doi: 10.1038/s41432-020-0099-1. PMID: 32591651; PMCID: PMC7317247.

3: Carrouel F, Gonçalves LS, Conte MP, Campus G, Fisher J, Fraticelli L, Gadea- Deschamps E, Ottolenghi L, Bourgeois D. Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2. J Dent Res. 2021 Feb;100(2):124-132. doi: 10.1177/0022034520967933.

Epub 2020 Oct 22. PMID: 33089717; PMCID: PMC7582358.

4: Kronbichler A, Effenberger M, Eisenhut M, Lee KH, Shin JI. Seven recommendations to rescue the patients and reduce the mortality from COVID-19 infection: An immunological point of view. Autoimmun Rev. 2020 Jul;19(7):102570. doi: 10.1016/j.autrev.2020.102570.

Epub 2020 May 3. PMID: 32376397; PMCID: PMC7252097.

5: Baker N, Williams AJ, Tropsha A, Ekins S. Repurposing Quaternary Ammonium Compounds as Potential Treatments for COVID-19. Pharm Res. 2020 May 25;37(6):104. doi: 10.1007/s11095-020-02842-8. PMID: 32451736; PMCID: PMC7247743.

6: Moosavi MS, Aminishakib P, Ansari M. Antiviral mouthwashes: possible benefit for COVID-19 with evidence-based approach. J Oral Microbiol. 2020 Jul 17;12(1):1794363. doi: 10.1080/20002297.2020.1794363. PMID: 32944152; PMCID: PMC7482897.

7: Caruso AA, Del Prete A, Lazzarino AI. Hydrogen peroxide and viral infections: A literature review with research hypothesis definition in relation to the current covid-19 pandemic. Med Hypotheses. 2020 Nov;144:109910. doi: 10.1016/j.mehy.2020.109910. Epub 2020 Jun 1. PMID: 32505069; PMCID: PMC7262503.

8: Hopkins C, Alanin M, Philpott C, Harries P, Whitcroft K, Qureishi A, Anari S, Ramakrishnan Y, Sama A, Davies E, Stew B, Gane S, Carrie S, Hathorn I, Bhalla R, Kelly C, Hill N, Boak D, Nirmal Kumar B. Management of new onset loss of sense of smell during the COVID-19 pandemic - BRS Consensus Guidelines. Clin Otolaryngol. 2021 Jan;46(1):16-22. doi: 10.1111/coa.13636. Epub 2020 Sep 24. PMID: 32854169; PMCID: PMC7461026.

9: León Molina J, Abad-Corpa E. Disinfectants and antiseptics facing coronavirus: synthesis of evidence and recommendations. Enferm Clin. 2021 Feb;31 Suppl 1:S84-S88. English, Spanish. doi: 10.1016/j.enfcli.2020.05.013. Epub 2020 May 21. PMID: 32778501;

PMCID: PMC7241393.

10: Burton MJ, Clarkson JE, Goulao B, Glenny AM, McBain AJ, Schilder AG, Webster KE, Worthington HV. Antimicrobial mouthwashes (gargling) and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to improve patient outcomes and to protect healthcare workers treating them. Cochrane Database Syst Rev. 2020 Sep 16;9(9):CD013627. doi: 10.1002/14651858.CD013627.pub2. PMID: 32936948; PMCID: PMC8187985.

11: Stathis C, Victoria N, Loomis K, Nguyen SA, Eggers M, Septimus E, Safdar N. Review of the use of nasal and oral antiseptics during a global pandemic. Future Microbiol. 2021 Jan;16(2):119-130. doi: 10.2217/fmb-2020-0286. Epub 2021 Jan 19. PMID: 33464122;

PMCID: PMC7842245.

12: Ortega KL, Rech BO, El Haje GLC, Gallo CB, Pérez-Sayáns M, Braz-Silva PH. Do hydrogen peroxide mouthwashes have a virucidal effect? A systematic review. J Hosp Infect. 2020 Dec;106(4):657-662. doi: 10.1016/j.jhin.2020.10.003. Epub 2020 Oct 12. PMID:

33058941; PMCID: PMC7548555.

13: Sette-de-Souza PH, Soares Martins JC, Martins-de-Barros AV, Rodrigues Vieira B, Fernandes Costa MJ, da Costa Araújo FA. A critical appraisal of evidence in the use of preprocedural mouthwash to avoid SARS-CoV-2 transmission during oral interventions. Eur Rev Med Pharmacol Sci. 2020 Oct;24(19):10222-10224. doi: 10.26355/eurrev_202010_23245. PMID: 33090432.

14: Samaranayake LP, Fakhruddin KS, Buranawat B, Panduwawala C. The efficacy of bio-aerosol reducing procedures used in dentistry: a systematic review. Acta Odontol Scand. 2021 Jan;79(1):69-80. doi: 10.1080/00016357.2020.1839673. Epub 2020 Dec 14. PMID:

33307917.

15: Vargas-Buratovic JP, Verdugo-Paiva F, Véliz-Paiva C, López-Tagle E, Ahumada- Salinas A, Ortuño-Borroto D. Recomendaciones odontológicas en la pandemia COVID-19: revisión narrativa [Dental recommendations in the COVID-19 pandemic: A narrative review].

Medwave. 2020 Jun 1;20(4):e7916. Spanish. doi: 10.5867/medwave.2020.05.7916. PMID: 32678809.

16: Burton MJ, Clarkson JE, Goulao B, Glenny AM, McBain AJ, Schilder AG, Webster KE, Worthington HV. Use of antimicrobial mouthwashes (gargling) and nasal sprays by healthcare workers to protect them when treating patients with suspected or confirmed COVID- 19 infection. Cochrane Database Syst Rev. 2020 Sep 16;9(9):CD013626. doi: 10.1002/14651858.CD013626.pub2. PMID: 32936949; PMCID: PMC8202127.

17: Burton MJ, Clarkson JE, Goulao B, Glenny AM, McBain AJ, Schilder AG, Webster KE, Worthington HV. Antimicrobial mouthwashes (gargling) and nasal sprays to protect healthcare workers when undertaking aerosol-generating procedures (AGPs) on patients without suspected or confirmed COVID-19 infection. Cochrane Database Syst Rev. 2020 Sep 16;9(9):CD013628. doi: 10.1002/14651858.CD013628.pub2. PMID: 32936947; PMCID: PMC8188293.

18: Mendez J, Villasanti U. Use of povidone as a mouthrinse to decrease the viral load of Covid-19 before dental care: Review of the literature. Am J Dent. 2020 Oct;33(5):248-250. PMID: 33017527.

19: Testori T, Wang HL, Basso M, Bordini G, Dian A, Vitelli C, Miletic I, Del Fabbro M. COVID-19 and Oral Surgery: A narrative review of preoperative mouth rinses. Acta Stomatol Croat. 2020 Dec;54(4):431-441. doi: 10.15644/asc54/4/10. PMID: 33642607; PMCID:

PMC7871429.

20: Egido-Moreno S, Valls-Roca-Umbert J, Jané-Salas E, López-López J, Estrugo- Devesa A. COVID-19 and oral lesions, short communication and review. J Clin Exp Dent. 2021 Mar 1;13(3):e287-e294. doi: 10.4317/jced.57981. PMID: 33680331; PMCID: PMC7920556.

Chlorhexidine 1,2,3,6,10,11,14,19,21,26,27,29,31

Cationic bisguinide

‰ Broad spectrum

antibacterial activity.

Greatest effect on many gram +ve, gram –ve, aerobic and anaerobic bacteria

‰ Most effective mouthwash for reducing plaque and gingivitis

Acts by increasing cell wall permeability

‰ Interacts with fluoride and sodium lauryl sulfate of toothpaste, hence should be used .5 to 2 hrs after using tooth paste

Effective against lipid- enveloped viruses like influenza A, parainfluenza, herpes 1, hepatitis B

‰ Can inactivate covid and improve symptoms in covid +ve patients.

But studies show it has little effect against corona virus

‰ Side effects: Staining, metallic taste, loss of taste.

Povidone-iodine 1-4,6,10,11,14- 16,18,19,21,22,24-28,30,31

An iodophore

‰ Broad spectrum

antimicrobial activity Effective against a variety of bacteria, fungi, protozoans and viruses

‰ Shows affinity for cell membranes and delivers iodine to the cell surface which further penetrates and causes protein and nucleic acid oxidation Also effective against SARS- COV, MERS-COV, influenza A Has more antiviral properties than other (both for

enveloped and non-

enveloped) viruses

‰ Recommended conc.- 0.23% for 15 sec

‰ Side effects: Excess iodine intake may cause complications in patients with thyroid disease

Hydrogen peroxide 1,2,3,7,10- 12,14,15,19,21,26,27,31

A bleaching agent Has oxidising properties

‰ Broad spectrum

bactericidal agent

Used to relieve minor gingivitis Some products also have ethanol in addition as an antimicrobial, preservative and solvent

‰ Acts by liberating O2, hence killing obligate anaerobes

3% found effective against adenovirus type 3 and 6, adeno-associated virus type 4, rhinoviruse1A, 1B and type 7 Enveloped viruses can be inactivated by 0.5% H2O2

‰ Also effective against corona virus strains

Corona and influenza viruses are most sensitive (both are vulnerable to oxidation)

Methylene blue 33 Effective antioxidant

‰ As a bacteriostatic stain and as an indicator dye Used as urinary tract antiseptic and for neuroinflammation at the microglial level, oral mucositis, and as an early diagnostic tool for oral cancers and precancerous lesions Burak et al studied MB as a mouthwash for periodontal therapy and found it superior to chlorhexidine gluconate

‰ Three mechanisms of actions:

1.Competitively occupy cellular sites

2. By completing defective oxidative processes of cells or by uncoupling oxidation and phosphorylation

3.Direct or indirect virucidal effect

0.5% methylene blue can act as a potent antiviral agent

PORW26

ACE2

Cell Membrane

Potential Mechanisms Of Anti-SARS-CoV-2 Activity Of Mouth Rinses

1. Viral envelope(membrane) disruption - increased permeability, Lipid oxidation 2. Nucleic acid damage

3. Inactivation of viral glycoprotein 4. Blocking viral attachment via GAGs

5. Blocking the binding of spike proteins to ACE2 receptor

Glycosaminoglycans (GAGs) (eg: heparan sulphate)

5 5 1

2

3 4

Despite limited clinical evidence, we suggest the use of preprocedural mouthwashes in dental practice to reduce SARS- CoV-2 viral load of saliva and cross infection risk while treating the patients during this pandemic.

Materials & Method A literature search performed in PubMed, up to 31 st July 2021, focusing on SARS-CoV-2, COVID-19, oral cavity and oral rinses. The keywords searched for were “Covid 19 and mouthwash” or “SARS- COV2 and mouthwash” or “Covid 19 and oral rinses” or

“SARS-COV2 and oral rinses”, and 123 articles surfaced in 2020 and 2021. Inclusion criteria were systematic reviews and reviews; 34 articles formed a part of the poster.

Aim To evaluate the composition and mechanism of action of various oral rinses and their efficacy to reduce viral load in Covid-19 in published literature.

21: Pruthi G, Parkash H, Bharathi P V, Jain R, Gupta A, Rai S. Comprehensive review of guidelines to practice prosthodontic and implant procedures during COVID-19 pandemic. J Oral Biol Craniofac Res. 2020 Oct-Dec;10(4):768-775. doi:

10.1016/j.jobcr.2020.10.010. Epub 2020 Oct 17. PMID: 33101891; PMCID: PMC7568128.

22: Chorney SR, Rizzi MD, Dedhia K. Considerations for povidone-iodine antisepsis in pediatric nasal and pharyngeal surgery during the COVID-19 pandemic. Am J Otolaryngol. 2020 Nov-Dec;41(6):102737. doi: 10.1016/j.amjoto.2020.102737. Epub 2020 Sep 19. PMID: 32979667; PMCID: PMC7501061.

23: Klausner M, Handa Y, Aizawa S. In vitro three-dimensional organotypic culture models of the oral mucosa. In Vitro Cell Dev Biol Anim. 2021 Feb;57(2):148-159. doi: 10.1007/s11626-020-00539-1. Epub 2021 Jan 14. PMID: 33447968; PMCID:

PMC7808300.

24: Chowdhry A, Kapoor P, Kharbanda OP, Popli DB. Saliva and COVID 19: Current dental perspective. J Oral Maxillofac Pathol. 2021 Jan-Apr;25(1):18-21. doi: 10.4103/jomfp.jomfp_63_21. Epub 2021 May 14. PMID: 34349404; PMCID: PMC8272509.

25: Castro-Ruiz C, Vergara-Buenaventura A. Povidone-Iodine Solution: A Potential Antiseptic to Minimize the Risk of COVID-19? A Narrative Review. J Int Soc Prev Community Dent. 2020 Oct 19;10(6):681-685. doi: 10.4103/jispcd.JISPCD_304_20.

PMID: 33437699; PMCID: PMC7791588.

26: Mohamed NA, Ahmad Zainol Hady A, Abdul Aziz AH, Isahak I. Could antiseptic gargling prevent COVID-19? Trop Biomed. 2020 Dec 1;37(4):1141-1145. doi: 10.47665/tb.37.4.1141. PMID: 33612766.

27: Mateos-Moreno MV, Mira A, Ausina-Márquez V, Ferrer MD. Oral antiseptics against coronavirus: in-vitro and clinical evidence. J Hosp Infect. 2021 Jul;113:30-43. doi: 10.1016/j.jhin.2021.04.004. Epub 2021 Apr 15. PMID: 33865974; PMCID:

PMC8046704.

28: Chopra A, Sivaraman K, Radhakrishnan R, Balakrishnan D, Narayana A. Can povidone iodine gargle/mouthrinse inactivate SARS-CoV-2 and decrease the risk of nosocomial and community transmission during the COVID-19 pandemic? An evidence- based update. Jpn Dent Sci Rev. 2021 Nov;57:39-45. doi: 10.1016/j.jdsr.2021.03.001. Epub 2021 Mar 15. PMID: 33747261; PMCID: PMC7959263.

29: Assis MS, Araújo RAAM, Lopes AMM. Safety alert for hospital environments and health professional: chlorhexidine is ineffective for coronavirus. Rev Assoc Med Bras (1992). 2020 Sep 21;66Suppl 2(Suppl 2):124-129. doi: 10.1590/1806- 9282.66.S2.124. PMID: 32965370.

30: Benson KM, Mancini AA, Brodeur MR. A Review of Topical Povidone-iodine to Decrease Viral Load of COViD-19. Sr Care Pharm. 2021 May 1;36(5):238-241. doi: 10.4140/TCP.n.2021.238.. PMID: 33879284.

31: Cavalcante-Leão BL, de Araujo CM, Basso IB, Schroder AG, Guariza-Filho O, Ravazzi GC, Gonçalves FM, Zeigelboim BS, Santos RS, Stechman-Neto J. Is there scientific evidence of the mouthwashes effectiveness in reducing viral load in Covid- 19? A systematic review. J Clin Exp Dent. 2021 Feb 1;13(2):e179-e189. doi: 10.4317/jced.57406. PMID: 33575003; PMCID: PMC7864359.

32: Silva PUJ, Paranhos LR, Meneses-Santos D, Blumenberg C, Macedo DR, Cardoso SV. Combination of toothbrushing and chlorhexidine compared with exclusive use of chlorhexidine to reduce the risk of ventilator-associated pneumonia: A systematic review with meta-analysis. Clinics (Sao Paulo). 2021 Jun 11;76:e2659. doi: 10.6061/clinics/2021/e2659. PMID: 34133659; PMCID: PMC8158674.

33.Arakeri G, Rao US V. Methylene blue as an anti-COVID-19 mouthwash in dental practice. Br J Oral Maxillofac Surg (2020).

34.da Fonseca Orcina B, Vilhena FV, Cardoso de Oliveira R, et al. A Phthalocyanine Derivate Mouthwash to Gargling/Rinsing as an Option to Reduce Clinical Symptoms of COVID-19: Case Series.Clin Cosmet Investig Dent. 2021;13:47-50. Published 2021 Feb 18. doi:10.2147/CCIDE.S295423

Photos adapted from: Subramanian Boopathi, Adolfo B. Poma & Ponmalai Kolandaivel (2021) Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment, Journal of Biomolecular Structure and Dynamics, 39:9, 3409-3418, DOI: 10.1080/07391102.2020.1758788.

Xu, C.;Wang, A.; Hoskin, E.R.; Cugini, C.; Markowitz, K.; Chang, T.L.; Fine, D.H. Differential Effects of Antiseptic Mouth Rinses on SARS-CoV-2 Infectivity In Vitro. Pathogens 2021, 10, 272. https:// doi.org/10.3390/pathogens10030272.

Boopathi S, Poma AB, Kolandaivel P. Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn. 2021;39(9):3409-3418. doi:10.1080/07391102.2020.1758788

Cetyl pyridinium chloride 1,3,5,19,21,27

‰ Cationic quaternary ammonium compound

Antiviral effect against influenza

‰ Effective against SARS-COV2 Lysomotrophic action and has ability to destroy viral capsid

Phthalocyanine Derivate 34

‰ Promising alternative to reduce viral load of SARS-CoV-2

Clinical improvement in cases with mild & moderate symptoms

‰ Promotes self activation &

continuous production of ROS in presence of molecular O 2

Herbal Triphala, curry leaves, neem, tulsi, green tea

Conclusion

References

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