Exploring Chemotherapeutic Agents as Countermeasures against Respiratory Viruses: Antiviral Potential of Sugar Alcohols
Main Article Content
Abstract
The emergence of respiratory viruses has been attracting considerable interest due to their potential to cause pandemics, such as the 1918 Spanish flu, the 2019 Coronavirus disease, and recently the Respiratory syncytial virus (RSV) in pediatric populations. There is a critical need to identify potential agents that can be included as part of the countermeasures to aid in the preparedness for a rapid public health response in case of a pandemic. This study aimed to explore the antiviral potential of sugar alcohols against respiratory viruses with pandemic potential.
Methods: The antiviral activity of three sugar alcohols commonly utilized in the food and pharmaceutical industry, namely sorbitol, erythritol, and xylitol, were evaluated against Influenza (H1N1), RSV (A2), and SARS-CoV-2 (B.1.617.2; Delta) via a highly differentiated, three-dimensional, in vitro model of normal, intact, human-derived tracheal/bronchial epithelial cells. The sugar alcohol solutions were tested at a 5% concentration in duplicate inserts of the three-dimensional tissue models of the human airway.
Results: Antiviral activity was measured in virus yield reduction assays by calculating the log reduction value defined as the average reduction of virus compared to the average virus control on day 3 (Influenza), day (RSV), and day 6 (SARS-CoV-2) after infection. Antiviral agents utilized as comparators were Ribavirin (Influenza, RSV) and Remdesivir (SARS-CoV-2). Erythritol displayed antiviral efficacy against Influenza with a log reduction value of 3.17. RSV was effectively inactivated by both sorbitol and xylitol with 2.49 and 2.65 log reduction values, respectively. All tested sugar alcohols inactivated SARS-CoV-2 Delta with a median log reduction value of 3.50.
Conclusion: The results of this study suggest that alone or in combination, sugar alcohols can inactivate respiratory viruses known to have pandemic potential. Additional research is needed to advance the development of sugar alcohols as chemotherapeutic countermeasures against other pandemic respiratory viruses.
Article Details
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References
2. Baker RE, Mahmud AS, Miller IF, et al. Infectious disease in an era of global change. Nat Rev Microbiol 2022;20(4):193-205. doi: 10.1038/s41579-021-00639-z [published Online First: 20211013]
3. Vila J, Lera E, Peremiquel-Trillas P, et al. Increased Rsv-A Bronchiolitis Severity In Rsv Infected Children Admitted To A Reference Center In Catalonia (Spain) Between 2014 And 2018. J Pediatric Infect Dis Soc 2023 doi: 10.1093/jpids/piad009 [published Online First: 20230206]
4. Silva PAN, Ito CRM, Moreira ALE, et al. Influenza and other respiratory viruses in children: prevalence and clinical features. Eur J Clin Microbiol Infect Dis 2022 doi: 10.1007/s10096-022-04515-3 [published Online First: 20221026]
5. Gholipour HF, Tajaddini R, Farzanegan MR. Governments' economic support for households during the COVID-19 pandemic and consumer confidence. Empir Econ 2023:1-20. doi: 10.1007/s00181-023-02367-0 [published Online First: 20230201]
6. Li L, Serido J, Vosylis R, et al. Employment Disruption and Wellbeing Among Young Adults: A Cross-National Study of Perceived Impact of the COVID-19 Lockdown. J Happiness Stud 2023:1-22. doi: 10.1007/s10902-023-00629-3 [published Online First: 20230207]
7. Noureddine O, ISSAOUI N, Al-Dossary O. DFT and molecular docking study of chloroquine derivatives as antiviral to coronavirus COVID-19. Journal of King Saud University Science 2020;33:101248 - 48.
8. Reznikov LR, Norris MH, Vashisht R, et al. Identification of antiviral antihistamines for COVID-19 repurposing. Biochem Biophys Res Commun 2021;538:173-79. doi: 10.1016/j.bbrc.2020.11.095 [published Online First: 2020/12/15]
9. Mostafa A, Kandeil A, Y AMME, et al. FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2. Pharmaceuticals (Basel) 2020;13(12) doi: 10.3390/ph13120443 [published Online First: 2020/12/10]
10. Kutkat O, Moatasim Y, Al-Karmalawy AA, et al. Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies. Sci Rep 2022;12(1):12920. doi: 10.1038/s41598-022-17082-6 [published Online First: 20220728]
11. Abbasi AR, Liu J, Wang Z, et al. Recent Advances in Producing Sugar Alcohols and Functional Sugars by Engineering Yarrowia lipolytica. Front Bioeng Biotechnol 2021;9:648382. doi: 10.3389/fbioe.2021.648382 [published Online First: 20210311]
12. Park Y-C, Oh EJ, Jo J-H, et al. Recent advances in biological production of sugar alcohols. Current Opinion in Biotechnology 2016;37:105-13. doi: https://doi.org/10.1016/j.copbio.2015.11.006
13. Ur-Rehman S, Mushtaq Z, Zahoor T, et al. Xylitol: a review on bioproduction, application, health benefits, and related safety issues. Critical reviews in food science and nutrition 2015;55(11):1514-28. doi: 10.1080/10408398.2012.702288 [published Online First: 2014/06/11]
14. Bansal S, Jonsson CB, Taylor SL, et al. Iota-carrageenan and xylitol inhibit SARS-CoV-2 in Vero cell culture. PLoS One 2021;16(11):e0259943. doi: 10.1371/journal.pone.0259943 [published Online First: 20211119]
15. de Cock P, Mäkinen K, Honkala E, et al. Erythritol Is More Effective Than Xylitol and Sorbitol in Managing Oral Health Endpoints. Int J Dent 2016;2016:9868421. doi: 10.1155/2016/9868421 [published Online First: 2016/09/17]
16. Jones AH. The next step in infectious disease: taming bacteria. Med Hypotheses 2003;60(2):171-4. doi: 10.1016/s0306-9877(02)00352-3 [published Online First: 2003/02/28]
17. Haukioja A, Söderling E, Tenovuo J. Acid production from sugars and sugar alcohols by probiotic lactobacilli and bifidobacteria in vitro. Caries Res 2008;42(6):449-53. doi: 10.1159/000163020 [published Online First: 2008/10/22]
18. Xu ML, Wi GR, Kim HJ, et al. Ameliorating Effect of Dietary Xylitol on Human Respiratory Syncytial Virus (hRSV) Infection. Biol Pharm Bull 2016;39(4):540-6. doi: 10.1248/bpb.b15-00773 [published Online First: 2016/04/05]
19. Weissman JD, Fernandez F, Hwang PH. Xylitol nasal irrigation in the management of chronic rhinosinusitis: a pilot study. Laryngoscope 2011;121(11):2468-72. doi: 10.1002/lary.22176 [published Online First: 2011/10/14]
20. Akgül Ö, Ak A, Zorlu S, et al. Effects of short-term xylitol chewing gum on pro-inflammatory cytokines and Streptococcus mutans: a randomized, placebo-controlled trial. Int J Clin Pract 2020:e13623. doi: 10.1111/ijcp.13623 [published Online First: 2020/07/31]
21. Nagarajan N, Yapp EKY, Le NQK, et al. In silico screening of sugar alcohol compounds to inhibit viral matrix protein VP40 of Ebola virus. Mol Biol Rep 2019;46(3):3315-24. doi: 10.1007/s11033-019-04792-w [published Online First: 20190413]
22. Salli K, Lehtinen MJ, Tiihonen K, et al. Xylitol's Health Benefits beyond Dental Health: A Comprehensive Review. Nutrients 2019;11(8) doi: 10.3390/nu11081813 [published Online First: 2019/08/09]
23. Reed LJ, Muench H. A Simple method of estimating fifty per cent endpoints12. American Journal of Epidemiology 1938;27(3):493-97. doi: 10.1093/oxfordjournals.aje.a118408
24. Ferrer G, Betancourt A, Go CC, et al. A Nasal Spray Solution of Grapefruit Seed Extract plus Xylitol Displays Virucidal Activity Against SARS-Cov-2 In Vitro. bioRxiv 2020:2020.11.23.394114. doi: 10.1101/2020.11.23.394114
25. Cheudjeu A. Correlation of D-xylose with severity and morbidity-related factors of COVID-19 and possible therapeutic use of D-xylose and antibiotics for COVID-19. Life Sci 2020;260:118335. doi: 10.1016/j.lfs.2020.118335 [published Online First: 2020/08/28]
26. Ciprandi G, La Mantia I, Brunese FP, et al. Hypertonic saline with xylitol and hyaluronate may shorten the viral shedding duration in asymptomatic COVID-19 positive subjects: a pilot study. J Biol Regul Homeost Agents 2021;35(3):1151-54. doi: 10.23812/21-138-l [published Online First: 2021/07/08]
27. Cegolon L, Mastrangelo G, Emanuelli E, et al. Early Negativization of SARS-CoV-2 Infection by Nasal Spray of Seawater plus Additives: The RENAISSANCE Open-Label Controlled Clinical Trial. Pharmaceutics 2022;14(11):2502.
28. Soler E, de Mendoza A, Cuello VI, et al. Intranasal Xylitol for the Treatment of COVID-19 in the Outpatient Setting: A Pilot Study. Cureus 2022;14(7):e27182. doi: 10.7759/cureus.27182 [published Online First: 20220723]
29. Go CC, Pandav K, Sanchez-Gonzalez MA, et al. Potential Role of Xylitol Plus Grapefruit Seed Extract Nasal Spray Solution in COVID-19: Case Series. Cureus 2020;12(11):e11315. doi: 10.7759/cureus.11315 [published Online First: 2020/11/12]
30. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020;181(2):271-80.e8. doi: 10.1016/j.cell.2020.02.052 [published Online First: 2020/03/07]
31. Lo MK, Spengler JR, Krumpe LRH, et al. Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge. J Infect Dis 2020;221(Supplement_4):S480-s92. doi: 10.1093/infdis/jiz630 [published Online First: 2020/02/11]
32. Ferrer G, Sanchez-Gonzalez MA. Effective Nasal Disinfection as an Overlooked Strategy in Our Fight against COVID-19. Ear Nose Throat J 2021:1455613211002929. doi: 10.1177/01455613211002929 [published Online First: 2021/03/27]