Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2

F Carrouel, L S Gonçalves, M P Conte, G Campus, J Fisher, L Fraticelli, E Gadea-Deschamps, L Ottolenghi, D Bourgeois, F Carrouel, L S Gonçalves, M P Conte, G Campus, J Fisher, L Fraticelli, E Gadea-Deschamps, L Ottolenghi, D Bourgeois

Abstract

The oral cavity, an essential part of the upper aerodigestive tract, is believed to play an important role in the pathogenicity and transmission of SARS-CoV-2. The identification of targeted antiviral mouth rinses to reduce salivary viral load would contribute to reducing the COVID-19 pandemic. While awaiting the results of significant clinical studies, which to date do not exist, the commercial availability of mouth rinses leads us to search among them for reagents that would have specific antiviral properties with respect to SARS-CoV-2. The challenges facing this target were examined for 7 reagents found in commercially available mouth rinses and listed on the ClinicalTrials.gov website: povidone-iodine, chlorhexidine, hydrogen peroxide, cyclodextrin, Citrox, cetylpyridinium chloride, and essential oils. Because SARS-CoV-2 is an enveloped virus, many reagents target the outer lipid membrane. Moreover, some of them can act on the capsid by denaturing proteins. Until now, there has been no scientific evidence to recommend mouth rinses with an anti-SARS-CoV-2 effect to control the viral load in the oral cavity. This critical review indicates that current knowledge of these reagents would likely improve trends in salivary viral load status. This finding is a strong sign to encourage clinical research for which quality protocols are already available in the literature.

Keywords: COVID-19; clinical trial; mouthwashes; oral; saliva; viral load.

Conflict of interest statement

Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Current status of clinical trials on the use of mouth rinse for COVID-19 listed on the site ClinicalTrials.gov (Find Trials 2020).

References

    1. Abu-Farha M, Thanaraj TA, Qaddoumi MG, Hashem A, Abubaker J, Al-Mulla F. 2020. The role of lipid metabolism in COVID-19 virus infection and as a drug target. Int J Mol Sci. 21(10):3544.
    1. Alharbi A, Alharbi S, Alqaidi S. 2020. Guidelines for dental care provision during the COVID-19 pandemic. Saudi Dent J. 32(4):181–186.
    1. American Dental Association. 2020. American Dental Association (ADA) interim guidance for minimizing risk of COVID-19 transmission; [accessed 2020 Aug 26]. .
    1. Anderson DE, Sivalingam V, Kang AEZ, Ananthanarayanan A, Arumugam H, Jenkins TM, Hadjiat Y, Eggers M. 2020. Povidone-iodine demonstrates rapid in vitro virucidal activity against SARS-CoV-2, the virus causing COVID-19 disease. Infect Dis Ther. 9(3):669–675.
    1. Asif M, Saleem M, Saadullah M, Yaseen HS, Al Zarzour R. 2020. COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties. Inflammopharmacology. 28(5):1153–1161.
    1. Ather A, Patel B, Ruparel NB, Diogenes A, Hargreaves KM. 2020. Coronavirus disease 19 (COVID-19): implications for clinical dental care. J Endod. 46(5):584–595.
    1. Australian Dental Association. 2020. ADA COVID-19 risk management guidance; [accessed 2020 Aug 26]. .
    1. Baghizadeh Fini M. 2020. a. Oral saliva and COVID-19. Oral Oncol. 108:104821.
    1. Baghizadeh Fini M. 2020. b. What dentists need to know about COVID-19. Oral Oncol. 105:104741.
    1. Baker N, Williams AJ, Tropsha A, Ekins S. 2020. Repurposing quaternary ammonium compounds as potential treatments for COVID-19. Pharm Res. 37(6):104.
    1. Bernstein D, Schiff G, Echler G, Prince A, Feller M, Briner W. 1990. In vitro virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse. J Dent Res. 69(3):874–876.
    1. Bidra AS, Pelletier JS, Westover JB, Frank S, Brown SM, Tessema B. 2020. Comparison of in vitro inactivation of SARS CoV-2 with hydrogen peroxide and povidone-iodine oral antiseptic rinses. J Prosthodont. 2020;29(7):599–603.
    1. Braga SS. 2019. Cyclodextrins: emerging medicines of the new millennium. Biomolecules. 9(12):801.
    1. Carrouel F, Conte MP, Fisher J, Gonçalves LS, Dussart C, Llodra JC, Bourgeois D. 2020. COVID-19: a recommendation to examine the effect of mouthrinses with β-cyclodextrin combined with citrox in preventing infection and progression. J Clin Med. 9(4):1126.
    1. Caruso AA, Del Prete A, Lazzarino AI, Capaldi R, Grumetto L. 2020. Might hydrogen peroxide reduce the hospitalization rate and complications of SARS-CoV-2 infection? Infect Control Hosp Epidemiol. 41(11):1360–1361.
    1. Centers for Disease Control and Prevention. 2020. Guidance for dental settings: interim infection prevention and control guidance for dental settings during the coronavirus disease 2019 (COVID-19) pandemic; [accessed 2020 Aug 26].
    1. Challacombe SJ, Kirk-Bayley J, Sunkaraneni VS, Combes J. 2020. Povidone iodine. Br Dent J. 228(9):656–657.
    1. Chen YW, Yiu CPB, Wong KY. 2020. Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CLpro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. F1000Res. 9:129.
    1. Elfiky AA, Ibrahim IM. 2020. Zika virus envelope—heat shock protein A5 (GRP78) binding site prediction 2020. J Biomol Struct Dyn [epub ahead of print 24 Jun 2020]. doi:10.1080/07391102.2020.1784794
    1. Find Trials. 2020. ; [accessed 2020 Aug 26].
    1. Frank S, Capriotti J, Brown SM, Tessema B. 2020. Povidone-iodine use in sinonasal and oral cavities: a review of safety in the COVID-19 era. Ear Nose Throat J. 99(9):586–593.
    1. Gottsauner MJ, Michaelides I, Schmidt B, Scholz KJ, Buchalla W, Widbiller M, Hitzenbichler F, Ettl T, Reichert TE, Bohr C, et al. 2020. A prospective clinical pilot study on the effects of a hydrogen peroxide mouthrinse on the intraoral viral load of SARS-CoV-2. Clin Oral Investig. 24(10):3707–3713.
    1. Gray PEA, Katelaris CH, Lipson D. 2013. Recurrent anaphylaxis caused by topical povidone-iodine (Betadine). J Paediatr Child Health. 49(6):506–507.
    1. Hassandarvish P, Tiong V, Sazaly AB, Mohamed NA, Arumugam H, Ananthanarayanan A, Qasuri M, Hadjiat M. 2020. Povidone iodine gargle and mouthwash. Br Dent J. 228(12):900.
    1. Herrera D, Serrano J, Roldán S, Sanz M. 2020. Is the oral cavity relevant in SARS-CoV-2 pandemic? Clin Oral Investig. 24(8):2925–2930.
    1. Hooper SJ, Lewis MAO, Wilson MJ, Williams DW. 2011. Antimicrobial activity of Citrox bioflavonoid preparations against oral microorganisms. Br Dent J. 210(1):E22.
    1. Hu X, Cai X, Song X, Li C, Zhao J, Luo W, Zhang Q, Ekumi IO, He Z. 2020. Possible SARS-coronavirus 2 inhibitor revealed by simulated molecular docking to viral main protease and host toll-like receptor. Future Virol [epub ahead of print May 2020]. doi:10.2217/fvl-2020-0099
    1. Jayaweera M, Perera H, Gunawardana B, Manatunge J. 2020. Transmission of COVID-19 virus by droplets and aerosols: a critical review on the unresolved dichotomy. Environ Res. 188:109819.
    1. Jing JLJ, Pei Yi T, Bose RJC, McCarthy JR, Tharmalingam N, Madheswaran T. 2020. Hand sanitizers: a review on formulation aspects, adverse effects, and regulations. Int J Environ Res Public Health. 17(9):3326.
    1. Kawana R, Kitamura T, Nakagomi O, Matsumoto I, Arita M, Yoshihara N, Yanagi K, Yamada A, Morita O, Yoshida Y, et al. 1997. Inactivation of human viruses by povidone-iodine in comparison with other antiseptics. Dermatology. 195 Suppl 2:29–35.
    1. Kulkarni SA, Nagarajan SK, Ramesh V, Palaniyandi V, Selvam SP, Madhavan T. 2020. Computational evaluation of major components from plant essential oils as potent inhibitors of SARS-CoV-2 spike protein. J Mol Struct. 1221:128823.
    1. Kumar GD, Mishra A, Dunn L, Townsend A, Oguadinma IC, Bright KR, Gerba CP. 2020. Biocides and novel antimicrobial agents for the mitigation of coronaviruses. Front Microbiol. 11:1351.
    1. Lachapelle J-M. 2014. A comparison of the irritant and allergenic properties of antiseptics. Eur J Dermatol. 24(1):3–9.
    1. Lalani S, Poh CL. 2020. Flavonoids as antiviral agents for enterovirus A71 (EV-A71). Viruses. 12(2):184.
    1. Martínez Lamas L, Diz Dios P, Pérez Rodríguez MT, Del Campo P, Cabrera Alvargonzalez JJ, López Domínguez AM, Fernandez Feijoo J, Diniz Freitas M, Limeres Posse J. 2020. Is povidone-iodine mouthwash effective against SARS-CoV-2? First in vivo tests. Oral Dis [epub ahead of print 2 Jul 2020]. doi:10.1111/odi.13526
    1. Meneguzzo F, Ciriminna R, Zabini F, Pagliaro M. 2020. Review of evidence available on hesperidin-rich products as potential tools against COVID-19 and hydrodynamic cavitation-based extraction as a method of increasing their production. Processes. 8(5):549.
    1. Nagatake T, Ahmed K, Oishi K. 2002. Prevention of respiratory infections by povidone-iodine gargle. Dermatology. 204 Suppl 1:32–36.
    1. National Academies of Sciences, Engineering, and Medicine. 2020. Rapid expert consultation on the possibility of bioaerosol spread of SARS-CoV-2 for the COVID-19 pandemic (April 1, 2020). Washington (DC): National Academies Press (US) [accessed 2020 Aug 26]. 10.17226/25784
    1. Ngwa W, Kumar R, Thompson D, Lyerly W, Moore R, Reid T-E, Lowe H, Toyang N. 2020. Potential of flavonoid-inspired phytomedicines against COVID-19. Molecules. 25(11):2707.
    1. O’Donnell VB, Thomas D, Stanton R, Maillard JY, Murphy RC, Jones SA, Humphreys I, Wakelam MJO, Fegan C, Wise MP, et al. 2020. Potential role of oral rinses targeting the viral lipid envelope in SARS-CoV-2 infection. Function. 1(1):zqaa002.
    1. Ortega KL, Rodrigues de Camargo A, Bertoldi Franco J, Mano Azul A, Pérez Sayáns M, Braz Silva PH. 2020. SARS-CoV-2 and dentistry. Clin Oral Investig. 24(7):2541–2542.
    1. Pattanshetty S, Narayana A, Radhakrishnan R. 2020. Povidone-iodine gargle as a prophylactic intervention to interrupt the transmission of SARS-CoV-2. Oral Dis [epub ahead of print 30 Apr 2020]. doi:10.1111/odi.13378
    1. Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. 2020. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci. 12(1):9.
    1. Reis ACC, Silva BM, de Moura HMM, Pereira GR, Brandão GC. 2020. Anti-Zika virus activity and chemical characterization by ultra-high performance liquid chromatography (UPLC-DAD-UV-MS) of ethanol extracts in Tecoma species. BMC Complement Med Ther. 20(1):246.
    1. Shang J, Wan Y, Luo C, Ye G, Geng Q, Auerbach A, Li F. 2020. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A. 117(21):11727–11734.
    1. Shen L, Niu J, Wang C, Huang B, Wang W, Zhu N, Deng Y, Wang H, Ye F, Cen S, et al. 2019. High-throughput screening and identification of potent broad-spectrum inhibitors of coronaviruses. J Virol. 93(12):e00023-19.
    1. Shiraishi T, Nakagawa Y. 2002. Evaluation of the bactericidal activity of povidone-iodine and commercially available gargle preparations. Dermatology. 204 Suppl 1:37–41.
    1. Silva JKRD, Figueiredo PLB, Byler KG, Setzer WN. 2020. Essential oils as antiviral agents. Potential of essential oils to treat SARS-CoV-2 infection: an in-silico investigation; Int J Mol Sci. 21(10):3426.
    1. Thuy BTP, My TTA, Hai NTT, Hieu LT, Hoa TT, Loan HTP, Triet NT, Anh TTV, Quy PT, Tat PV, et al. 2020. Investigation into SARS-CoV-2 resistance of compounds in garlic essential oil. ACS Omega. 5(14):8312–8320.
    1. To KK, Tsang OT, Yip CC, Chan KH, Wu TC, Chan JM, Leung WS, Chik TS, Choi CY, Kandamby DH, et al. 2020. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis. 71(15):841–843.
    1. Tsuda S, Soutome S, Hayashida S, Funahara M, Yanamoto S, Umeda M. 2020. Topical povidone iodine inhibits bacterial growth in the oral cavity of patients on mechanical ventilation: a randomized controlled study. BMC Oral Health. 20(1):62.
    1. Wińska K, Mączka W, Łyczko J, Grabarczyk M, Czubaszek A, Szumny A. 2019. Essential oils as antimicrobial agents-myth or real alternative? Molecules. 24(11):2130.
    1. Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, Wang Q, Xu Y, Li M, Li X, et al. 2020. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B. 10(5):766–788.
    1. Xu R, Cui B, Duan X, Zhang P, Zhou X, Yuan Q. 2020. Saliva: potential diagnostic value and transmission of 2019-nCoV. Int J Oral Sci. 12(1):11.
    1. Yoon JG, Yoon J, Song JY, Yoon SY, Lim CS, Seong H, Noh JY, Cheong HJ, Kim WJ. 2020. Clinical significance of a high SARS-CoV-2 viral load in the saliva. J Korean Med Sci. 35(20):e195.
    1. Zhou L, Xu Z, Castiglione GM, Soiberman US, Eberhart CG, Duh EJ. 2020. ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. Ocul Surf. 18(4):537–544.
    1. Zou M, Liu H, Li J, Yao X, Chen Y, Ke C, Liu S. 2020. Structure-activity relationship of flavonoid bifunctional inhibitors against Zika virus infection. Biochem Pharmacol. 177:113962.
    1. Zupin L, Pascolo L, Crovella S. 2020. Is FURIN gene expression in salivary glands related to SARS-CoV-2 infectivity through saliva? J Clin Pathol [epub ahead of print 13 Jul 2020]. doi:10.1136/jclinpath-2020-206788

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