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Исследование потенциала препаратов на основе экстрактов лекарственных растений в отношении подавления репликации SARS-CoV-2: пилотное исследование*
Исследование потенциала препаратов на основе экстрактов лекарственных растений в отношении подавления репликации SARS-CoV-2: пилотное исследование*
Де Пеллегрин М.Л., Рорхофер А., Шустер Ф., Шмидт Б., Петербурс Ф., Гесснер А. Исследование потенциала препаратов на основе экстрактов лекарственных растений в отношении подавления репликации SARS-CoV-2: пилотное исследование. Consilium Medicum. 2021; 23 (9): 445–450. DOI: 10.26442/20751753.2021.9.200989
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Аннотация
Актуальность. Лекарственные средства растительного происхождения давно и успешно применяются в лечении самых разных заболеваний, в том числе и вирусной этиологии. Тем не менее до настоящего времени не изучалось их влияние на репликацию коронавируса тяжелого острого респираторного синдрома-2 (SARS-CoV-2).
Цель. Оценить потенциал препаратов на основе валидированных растительных экстрактов – РЭ (Бронхипрет, Бронхипрет ТП, Тонзилгон Н, Синупрет экстракт, Тонзипрет) в отношении их способности к подавлению репликации SARS-CoV-2 in vitro.
Материалы и методы. Клетки Веро (Vero), инкубированные с РЭ различной концентрации, были инфицированы вирусом SARS-CoV-2. Через 48 ч репликация вируса (количество копий вирусной РНК в супернатанте клеточной культуры) определялась методом количественной полимеразной цепной реакции.
Результаты. Количество копий РНК SARS-CoV-2 под действием нецитотоксических концентраций препарата Бронхипрет ТП снизилось
в 1 тыс. раз, а в результате воздействия препаратов Тонзилгон Н и Тонзипрет – в 10 раз.
Заключение. Некоторые из исследуемых РЭ in vitro продемонстрировали многообещающую противовирусную активность. Целесообразно проведение дальнейших, в том числе клинических, исследований их активности в отношении SARS-CoV-2 при лечении коронавирусной инфекции (COronaVirus Disease 2019 – COVID-19).
Ключевые слова: SARS-CoV-2, COVID-19, репликация вируса, растительные препараты, Бронхипрет, Бронхипрет ТП, Тонзилгон Н, Синупрет экстракт, Тонзипрет
Objective. To evaluate the potential of drugs based on validated plant extracts – RE (Bronchipret, Bronchipret TP, Tonsilgon N, Sinupret extract, Tonsipret) with respect to their ability to suppress SARS-CoV-2 replication in vitro.
Materials and methods. Vero cells (Vero) incubated with RE of different concentrations were infected with SARS-CoV-2 virus. After 48 h the virus replication (the number of viral RNA copies in cell culture supernatant) was determined by quantitative polymerase chain reaction.
Results. SARS-CoV-2 RNA copy number under the action of non-cytotoxic concentrations of Bronchipret TP decreased by 1000 times and by 10 times under the action of drugs Tonsilgon N and Tonsipret.
Conclusion. Some of the studied REs in vitro demonstrated promising antiviral activity. It is advisable to conduct further, including clinical, studies of their activity against SARS-CoV-2 in the treatment of coronavirus infection (COronaVirus Disease 2019 – COVID-19).
Keywords: SARS-CoV-2, COVID-19, virus replication, herbal medicines, Bronchipret, Bronchipret TP, Tonsilgon, Sinupret extract, Tonsipret
Цель. Оценить потенциал препаратов на основе валидированных растительных экстрактов – РЭ (Бронхипрет, Бронхипрет ТП, Тонзилгон Н, Синупрет экстракт, Тонзипрет) в отношении их способности к подавлению репликации SARS-CoV-2 in vitro.
Материалы и методы. Клетки Веро (Vero), инкубированные с РЭ различной концентрации, были инфицированы вирусом SARS-CoV-2. Через 48 ч репликация вируса (количество копий вирусной РНК в супернатанте клеточной культуры) определялась методом количественной полимеразной цепной реакции.
Результаты. Количество копий РНК SARS-CoV-2 под действием нецитотоксических концентраций препарата Бронхипрет ТП снизилось
в 1 тыс. раз, а в результате воздействия препаратов Тонзилгон Н и Тонзипрет – в 10 раз.
Заключение. Некоторые из исследуемых РЭ in vitro продемонстрировали многообещающую противовирусную активность. Целесообразно проведение дальнейших, в том числе клинических, исследований их активности в отношении SARS-CoV-2 при лечении коронавирусной инфекции (COronaVirus Disease 2019 – COVID-19).
Ключевые слова: SARS-CoV-2, COVID-19, репликация вируса, растительные препараты, Бронхипрет, Бронхипрет ТП, Тонзилгон Н, Синупрет экстракт, Тонзипрет
________________________________________________
Objective. To evaluate the potential of drugs based on validated plant extracts – RE (Bronchipret, Bronchipret TP, Tonsilgon N, Sinupret extract, Tonsipret) with respect to their ability to suppress SARS-CoV-2 replication in vitro.
Materials and methods. Vero cells (Vero) incubated with RE of different concentrations were infected with SARS-CoV-2 virus. After 48 h the virus replication (the number of viral RNA copies in cell culture supernatant) was determined by quantitative polymerase chain reaction.
Results. SARS-CoV-2 RNA copy number under the action of non-cytotoxic concentrations of Bronchipret TP decreased by 1000 times and by 10 times under the action of drugs Tonsilgon N and Tonsipret.
Conclusion. Some of the studied REs in vitro demonstrated promising antiviral activity. It is advisable to conduct further, including clinical, studies of their activity against SARS-CoV-2 in the treatment of coronavirus infection (COronaVirus Disease 2019 – COVID-19).
Keywords: SARS-CoV-2, COVID-19, virus replication, herbal medicines, Bronchipret, Bronchipret TP, Tonsilgon, Sinupret extract, Tonsipret
Полный текст
Список литературы
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28. Sharma A, Vora J, Patel D, et al. Identification of natural inhibitors against prime targets of SARS-CoV-2 using molecular docking, molecular dynamics simulation and MM-PBSA approaches. J Biomol Struct Dynamics. 2020:116.
DOI:10.1080/07391102.2020.1846624
29. Holzinger F, Chenot JF. Systematic review of clinical trials assessing the effectiveness of ivy leaf (hedera helix) for acute upper respiratory tract infections. Evid Based Complemen Alternat Med. 2011;2011:382789.
30. Müller M, Sewald K, Braun A, et al. Anti-inflammatory efficacy of the herbal medicinal product Bronchipret® tablets in murine respiratory syncytial virus lung infection. Keystone Symposia. Keystone, 2014.
31. Kemmerich B. Evaluation of efficacy and tolerability of a fixed combination of dry extracts of thyme herb and primrose root in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled multicentre clinical trial. Arzneimittelforschung. 2007;57(9):607-15.
32. Seibel J, Kryshen K, Pongrácz JE, Lehner MD. In vivo and in vitro investigation of anti-inflammatory and mucus-regulatory activities of a fixed combination of thyme and primula extracts. Pulm Pharmacol Ther. 2018;51:10-7.
33. Seibel J, Wonnemann M, Werz O, Lehner MD. A tiered approach to investigate the mechanism of anti-inflammatory activity of an herbal medicinal product containing a fixed combination of thyme herb and primula root extracts. Clin Phytosci. 2018;4(1):4.
34. Cho DY, Skinner D, Mackey C, et al. Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2019;9(6):629-37.
35. Rossi A, Dehm F, Kiesselbach C, et al. The novel Sinupret® dry extract exhibits anti-inflammatory effectiveness in vivo. Fitoterapia. 2012;83(4):715-20.
36. Kreindler JL, Chen B, Kreitman Y, et al. The novel dry extract BNO 1011 stimulates chloride transport and ciliary beat frequency in human respiratory epithelial cultures. Am J Rhinol Allergy. 2012;26(6):439-43.
37. Zupanets IA, Shebeko SK, Popovych VI, Zimin SM. Study of the anti-inflammatory effect of the combined extract BNO 1016 in a leukotriene-dependent in vivo inflammation model. Clin Phytosci. 2020;6(1):7.
38. Kemmerich B, Eberhardt R, Stammer H. Efficacy and tolerability of a fluid extract combination of thyme herb and ivy leaves and matched placebo in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled clinical trial. Arzneimittelforschung. 2006;56(9):652-60.
39. EMA. Committee on Herbal Medicinal Products (HMPC) Assessment report on Matricaria recutita L., flos and Matricaria recutita L., aetheroleum. 7 July 2015. EMA/HMPC/55837/2011 2015 [3 Dec 2020]. Available at: https://www.ema.europa.eu/en/documents/herbal-
report/final-assessment-report-matricaria-recutita-l-flos-matricaria-recutita-l-aetheroleum_en.pdf.Accessed: 01.06.2021.
https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed: 01.06.2021.
2. Tay MZP, Rénia CM. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363-74.
3. Cevik M, Kuppalli K, Kindrachuk J, Peiris M. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ. 2020;371:m3862.
4. Kaur SP, Gupta V. COVID-19 Vaccine: A comprehensive status report. Virus Res. 2020;288:198114.
5. Sahebnasagh A, Avan R, Saghafi F, et al. Pharmacological treatments of COVID-19. Pharmacol Rep. 2020;72(6):1446-78. DOI:10.1007/s43440-020-00152-9
6. Tu Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med. 2011;17(10):1217-20.
7. Akram M, Tahir IM, Shah SMA, et al. Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review. Phytother Res. 2018;32(5):811-22.
8. Popovych V, Koshel I, Malofiichuk A, et al. A randomized, open-label, multicenter, comparative study of therapeutic efficacy, safety and tolerability of BNO 1030 extract, containing marshmallow root, chamomile flowers, horsetail herb, walnut leaves, yarrow herb, oak bark, dandelion herb in the treatment of acute non-bacterial tonsillitis in children aged 6 to 18 years. Am J Otolaryngol. 2019;40(2):265-73.
9. Kim Y, Narayanan S, Chang KO. Inhibition of influenza virus replication by plant-derived isoquercetin. Antiviral Res. 2010;88(2):227-35.
10. Kashiwada Y, Aoshima A, Ikeshiro Y, et al. Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure-activity correlations with related alkaloids. Bioorg Med Chem. 2005;13(2):443-8.
11. Karimi A, Moradi MT, Saeedi M, et al. Antiviral activity of Quercus persica L.: High efficacy and low toxicity. Adv Biomed Res. 2013;2:36.
12. Popovich VI, Koshel IV. Dysbiosis of the nasopharynx in chronic adenoiditis associated with Epstein-Barr virus infection. The possibilities of its correction to determine the indications for adenotomy. Rynolohyya. 2015;2015(1):20-9.
13. Wosikowski K, Seifert S, Melnykov O, Haunschild J. Imupret® inhibits respiratory syncytial virus replication and displays in vitro and in vivo immunomodulatory properties. Planta Med. 2013;79:PB48.
14. Jund R, Mondigler M, Steindl H, et al. Clinical efficacy of a dry extract of five herbal drugs in acute viral rhinosinusitis. Rhinology. 2012;50(4):417-26.
15. Jund R, Mondigler M, Steindl H, et al. Clinical efficacy of a herbal drug combination in acute viral rhinosinusitis. MMW Fortschritte der Medizin. 2015;157(157 Suppl. 4):6-11.
16. Jund R, Mondigler M, Stammer H, et al. Herbal drug BNO 1016 is safe and effective in the treatment of acute viral rhinosinusitis. Acta Otolaryngol. 2015;135(1):42-50.
17. Seibel J, Pergola C, Werz O, et al. Bronchipret® syrup containing thyme and ivy extracts suppresses bronchoalveolar inflammation and goblet cell hyperplasia in experimental bronchoalveolitis. Phytomedicine. 2015;22(13):1172-7.
18. Melzer J, Saller R, Schapowal A, Brignoli R. Systematic review of clinical data with BNO-101 (Sinupret) in the treatment of sinusitis. Forsch Komplementmed. 2006;13(2):78-87.
19. Glatthaar-Saalmüller B, Rauchhaus U, Rode S, et al. Antiviral activity in vitro of two preparations of the herbal medicinal product Sinupret® against viruses causing respiratory infections. Phytomedicine. 2011;19(1):1-7.
20. Jureka AS, Silvas JA, Basler CF. Propagation, inactivation, and safety testing of SARS-CoV-2. Viruses. 2020;12(6):622.
21. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3):2000045.
22. Cory AH, Owen TC, Barltrop JA, Cory JG. Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Commun. 1991;3(7):207-12.
23. Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. Am J Epidemiol. 1938;27(3):493-7.
24. Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Military Med Res. 2020;7(1):4.
25. Zhou LK, Zhou Z, Jiang XM, et al. Absorbed plant MIR2911 in honeysuckle decoction inhibits SARS-CoV-2 replication and accelerates the negative conversion of infected patients. Cell Discov. 2020;6:54.
26. Khare P, Sahu U, Pandey SC, Samant M. Current approaches for target-specific drug discovery using natural compounds against SARS-CoV-2 infection. Virus Res. 2020;290:198169.
27. Mani JS, Johnson JB, Steel JC, et al. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020;284:197989.
28. Sharma A, Vora J, Patel D, et al. Identification of natural inhibitors against prime targets of SARS-CoV-2 using molecular docking, molecular dynamics simulation and MM-PBSA approaches. J Biomol Struct Dynamics. 2020:116.
DOI:10.1080/07391102.2020.1846624
29. Holzinger F, Chenot JF. Systematic review of clinical trials assessing the effectiveness of ivy leaf (hedera helix) for acute upper respiratory tract infections. Evid Based Complemen Alternat Med. 2011;2011:382789.
30. Müller M, Sewald K, Braun A, et al. Anti-inflammatory efficacy of the herbal medicinal product Bronchipret® tablets in murine respiratory syncytial virus lung infection. Keystone Symposia. Keystone, 2014.
31. Kemmerich B. Evaluation of efficacy and tolerability of a fixed combination of dry extracts of thyme herb and primrose root in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled multicentre clinical trial. Arzneimittelforschung. 2007;57(9):607-15.
32. Seibel J, Kryshen K, Pongrácz JE, Lehner MD. In vivo and in vitro investigation of anti-inflammatory and mucus-regulatory activities of a fixed combination of thyme and primula extracts. Pulm Pharmacol Ther. 2018;51:10-7.
33. Seibel J, Wonnemann M, Werz O, Lehner MD. A tiered approach to investigate the mechanism of anti-inflammatory activity of an herbal medicinal product containing a fixed combination of thyme herb and primula root extracts. Clin Phytosci. 2018;4(1):4.
34. Cho DY, Skinner D, Mackey C, et al. Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2019;9(6):629-37.
35. Rossi A, Dehm F, Kiesselbach C, et al. The novel Sinupret® dry extract exhibits anti-inflammatory effectiveness in vivo. Fitoterapia. 2012;83(4):715-20.
36. Kreindler JL, Chen B, Kreitman Y, et al. The novel dry extract BNO 1011 stimulates chloride transport and ciliary beat frequency in human respiratory epithelial cultures. Am J Rhinol Allergy. 2012;26(6):439-43.
37. Zupanets IA, Shebeko SK, Popovych VI, Zimin SM. Study of the anti-inflammatory effect of the combined extract BNO 1016 in a leukotriene-dependent in vivo inflammation model. Clin Phytosci. 2020;6(1):7.
38. Kemmerich B, Eberhardt R, Stammer H. Efficacy and tolerability of a fluid extract combination of thyme herb and ivy leaves and matched placebo in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled clinical trial. Arzneimittelforschung. 2006;56(9):652-60.
39. EMA. Committee on Herbal Medicinal Products (HMPC) Assessment report on Matricaria recutita L., flos and Matricaria recutita L., aetheroleum. 7 July 2015. EMA/HMPC/55837/2011 2015 [3 Dec 2020]. Available at: https://www.ema.europa.eu/en/documents/herbal-
report/final-assessment-report-matricaria-recutita-l-flos-matricaria-recutita-l-aetheroleum_en.pdf.Accessed: 01.06.2021.
https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed: 01.06.2021.
2. Tay MZP, Rénia CM. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363-74.
3. Cevik M, Kuppalli K, Kindrachuk J, Peiris M. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ. 2020;371:m3862.
4. Kaur SP, Gupta V. COVID-19 Vaccine: A comprehensive status report. Virus Res. 2020;288:198114.
5. Sahebnasagh A, Avan R, Saghafi F, et al. Pharmacological treatments of COVID-19. Pharmacol Rep. 2020;72(6):1446-78. DOI:10.1007/s43440-020-00152-9
6. Tu Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med. 2011;17(10):1217-20.
7. Akram M, Tahir IM, Shah SMA, et al. Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review. Phytother Res. 2018;32(5):811-22.
8. Popovych V, Koshel I, Malofiichuk A, et al. A randomized, open-label, multicenter, comparative study of therapeutic efficacy, safety and tolerability of BNO 1030 extract, containing marshmallow root, chamomile flowers, horsetail herb, walnut leaves, yarrow herb, oak bark, dandelion herb in the treatment of acute non-bacterial tonsillitis in children aged 6 to 18 years. Am J Otolaryngol. 2019;40(2):265-73.
9. Kim Y, Narayanan S, Chang KO. Inhibition of influenza virus replication by plant-derived isoquercetin. Antiviral Res. 2010;88(2):227-35.
10. Kashiwada Y, Aoshima A, Ikeshiro Y, et al. Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure-activity correlations with related alkaloids. Bioorg Med Chem. 2005;13(2):443-8.
11. Karimi A, Moradi MT, Saeedi M, et al. Antiviral activity of Quercus persica L.: High efficacy and low toxicity. Adv Biomed Res. 2013;2:36.
12. Popovich VI, Koshel IV. Dysbiosis of the nasopharynx in chronic adenoiditis associated with Epstein-Barr virus infection. The possibilities of its correction to determine the indications for adenotomy. Rynolohyya. 2015;2015(1):20-9.
13. Wosikowski K, Seifert S, Melnykov O, Haunschild J. Imupret® inhibits respiratory syncytial virus replication and displays in vitro and in vivo immunomodulatory properties. Planta Med. 2013;79:PB48.
14. Jund R, Mondigler M, Steindl H, et al. Clinical efficacy of a dry extract of five herbal drugs in acute viral rhinosinusitis. Rhinology. 2012;50(4):417-26.
15. Jund R, Mondigler M, Steindl H, et al. Clinical efficacy of a herbal drug combination in acute viral rhinosinusitis. MMW Fortschritte der Medizin. 2015;157(157 Suppl. 4):6-11.
16. Jund R, Mondigler M, Stammer H, et al. Herbal drug BNO 1016 is safe and effective in the treatment of acute viral rhinosinusitis. Acta Otolaryngol. 2015;135(1):42-50.
17. Seibel J, Pergola C, Werz O, et al. Bronchipret® syrup containing thyme and ivy extracts suppresses bronchoalveolar inflammation and goblet cell hyperplasia in experimental bronchoalveolitis. Phytomedicine. 2015;22(13):1172-7.
18. Melzer J, Saller R, Schapowal A, Brignoli R. Systematic review of clinical data with BNO-101 (Sinupret) in the treatment of sinusitis. Forsch Komplementmed. 2006;13(2):78-87.
19. Glatthaar-Saalmüller B, Rauchhaus U, Rode S, et al. Antiviral activity in vitro of two preparations of the herbal medicinal product Sinupret® against viruses causing respiratory infections. Phytomedicine. 2011;19(1):1-7.
20. Jureka AS, Silvas JA, Basler CF. Propagation, inactivation, and safety testing of SARS-CoV-2. Viruses. 2020;12(6):622.
21. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3):2000045.
22. Cory AH, Owen TC, Barltrop JA, Cory JG. Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Commun. 1991;3(7):207-12.
23. Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. Am J Epidemiol. 1938;27(3):493-7.
24. Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Military Med Res. 2020;7(1):4.
25. Zhou LK, Zhou Z, Jiang XM, et al. Absorbed plant MIR2911 in honeysuckle decoction inhibits SARS-CoV-2 replication and accelerates the negative conversion of infected patients. Cell Discov. 2020;6:54.
26. Khare P, Sahu U, Pandey SC, Samant M. Current approaches for target-specific drug discovery using natural compounds against SARS-CoV-2 infection. Virus Res. 2020;290:198169.
27. Mani JS, Johnson JB, Steel JC, et al. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020;284:197989.
28. Sharma A, Vora J, Patel D, et al. Identification of natural inhibitors against prime targets of SARS-CoV-2 using molecular docking, molecular dynamics simulation and MM-PBSA approaches. J Biomol Struct Dynamics. 2020:116.
DOI:10.1080/07391102.2020.1846624
29. Holzinger F, Chenot JF. Systematic review of clinical trials assessing the effectiveness of ivy leaf (hedera helix) for acute upper respiratory tract infections. Evid Based Complemen Alternat Med. 2011;2011:382789.
30. Müller M, Sewald K, Braun A, et al. Anti-inflammatory efficacy of the herbal medicinal product Bronchipret® tablets in murine respiratory syncytial virus lung infection. Keystone Symposia. Keystone, 2014.
31. Kemmerich B. Evaluation of efficacy and tolerability of a fixed combination of dry extracts of thyme herb and primrose root in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled multicentre clinical trial. Arzneimittelforschung. 2007;57(9):607-15.
32. Seibel J, Kryshen K, Pongrácz JE, Lehner MD. In vivo and in vitro investigation of anti-inflammatory and mucus-regulatory activities of a fixed combination of thyme and primula extracts. Pulm Pharmacol Ther. 2018;51:10-7.
33. Seibel J, Wonnemann M, Werz O, Lehner MD. A tiered approach to investigate the mechanism of anti-inflammatory activity of an herbal medicinal product containing a fixed combination of thyme herb and primula root extracts. Clin Phytosci. 2018;4(1):4.
34. Cho DY, Skinner D, Mackey C, et al. Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2019;9(6):629-37.
35. Rossi A, Dehm F, Kiesselbach C, et al. The novel Sinupret® dry extract exhibits anti-inflammatory effectiveness in vivo. Fitoterapia. 2012;83(4):715-20.
36. Kreindler JL, Chen B, Kreitman Y, et al. The novel dry extract BNO 1011 stimulates chloride transport and ciliary beat frequency in human respiratory epithelial cultures. Am J Rhinol Allergy. 2012;26(6):439-43.
37. Zupanets IA, Shebeko SK, Popovych VI, Zimin SM. Study of the anti-inflammatory effect of the combined extract BNO 1016 in a leukotriene-dependent in vivo inflammation model. Clin Phytosci. 2020;6(1):7.
38. Kemmerich B, Eberhardt R, Stammer H. Efficacy and tolerability of a fluid extract combination of thyme herb and ivy leaves and matched placebo in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled clinical trial. Arzneimittelforschung. 2006;56(9):652-60.
39. EMA. Committee on Herbal Medicinal Products (HMPC) Assessment report on Matricaria recutita L., flos and Matricaria recutita L., aetheroleum. 7 July 2015. EMA/HMPC/55837/2011 2015 [3 Dec 2020]. Available at: https://www.ema.europa.eu/en/documents/herbal-
report/final-assessment-report-matricaria-recutita-l-flos-matricaria-recutita-l-aetheroleum_en.pdf.Accessed: 01.06.2021.
________________________________________________
https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed: 01.06.2021.
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8. Popovych V, Koshel I, Malofiichuk A, et al. A randomized, open-label, multicenter, comparative study of therapeutic efficacy, safety and tolerability of BNO 1030 extract, containing marshmallow root, chamomile flowers, horsetail herb, walnut leaves, yarrow herb, oak bark, dandelion herb in the treatment of acute non-bacterial tonsillitis in children aged 6 to 18 years. Am J Otolaryngol. 2019;40(2):265-73.
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11. Karimi A, Moradi MT, Saeedi M, et al. Antiviral activity of Quercus persica L.: High efficacy and low toxicity. Adv Biomed Res. 2013;2:36.
12. Popovich VI, Koshel IV. Dysbiosis of the nasopharynx in chronic adenoiditis associated with Epstein-Barr virus infection. The possibilities of its correction to determine the indications for adenotomy. Rynolohyya. 2015;2015(1):20-9.
13. Wosikowski K, Seifert S, Melnykov O, Haunschild J. Imupret® inhibits respiratory syncytial virus replication and displays in vitro and in vivo immunomodulatory properties. Planta Med. 2013;79:PB48.
14. Jund R, Mondigler M, Steindl H, et al. Clinical efficacy of a dry extract of five herbal drugs in acute viral rhinosinusitis. Rhinology. 2012;50(4):417-26.
15. Jund R, Mondigler M, Steindl H, et al. Clinical efficacy of a herbal drug combination in acute viral rhinosinusitis. MMW Fortschritte der Medizin. 2015;157(157 Suppl. 4):6-11.
16. Jund R, Mondigler M, Stammer H, et al. Herbal drug BNO 1016 is safe and effective in the treatment of acute viral rhinosinusitis. Acta Otolaryngol. 2015;135(1):42-50.
17. Seibel J, Pergola C, Werz O, et al. Bronchipret® syrup containing thyme and ivy extracts suppresses bronchoalveolar inflammation and goblet cell hyperplasia in experimental bronchoalveolitis. Phytomedicine. 2015;22(13):1172-7.
18. Melzer J, Saller R, Schapowal A, Brignoli R. Systematic review of clinical data with BNO-101 (Sinupret) in the treatment of sinusitis. Forsch Komplementmed. 2006;13(2):78-87.
19. Glatthaar-Saalmüller B, Rauchhaus U, Rode S, et al. Antiviral activity in vitro of two preparations of the herbal medicinal product Sinupret® against viruses causing respiratory infections. Phytomedicine. 2011;19(1):1-7.
20. Jureka AS, Silvas JA, Basler CF. Propagation, inactivation, and safety testing of SARS-CoV-2. Viruses. 2020;12(6):622.
21. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3):2000045.
22. Cory AH, Owen TC, Barltrop JA, Cory JG. Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Commun. 1991;3(7):207-12.
23. Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. Am J Epidemiol. 1938;27(3):493-7.
24. Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Military Med Res. 2020;7(1):4.
25. Zhou LK, Zhou Z, Jiang XM, et al. Absorbed plant MIR2911 in honeysuckle decoction inhibits SARS-CoV-2 replication and accelerates the negative conversion of infected patients. Cell Discov. 2020;6:54.
26. Khare P, Sahu U, Pandey SC, Samant M. Current approaches for target-specific drug discovery using natural compounds against SARS-CoV-2 infection. Virus Res. 2020;290:198169.
27. Mani JS, Johnson JB, Steel JC, et al. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020;284:197989.
28. Sharma A, Vora J, Patel D, et al. Identification of natural inhibitors against prime targets of SARS-CoV-2 using molecular docking, molecular dynamics simulation and MM-PBSA approaches. J Biomol Struct Dynamics. 2020:116.
DOI:10.1080/07391102.2020.1846624
29. Holzinger F, Chenot JF. Systematic review of clinical trials assessing the effectiveness of ivy leaf (hedera helix) for acute upper respiratory tract infections. Evid Based Complemen Alternat Med. 2011;2011:382789.
30. Müller M, Sewald K, Braun A, et al. Anti-inflammatory efficacy of the herbal medicinal product Bronchipret® tablets in murine respiratory syncytial virus lung infection. Keystone Symposia. Keystone, 2014.
31. Kemmerich B. Evaluation of efficacy and tolerability of a fixed combination of dry extracts of thyme herb and primrose root in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled multicentre clinical trial. Arzneimittelforschung. 2007;57(9):607-15.
32. Seibel J, Kryshen K, Pongrácz JE, Lehner MD. In vivo and in vitro investigation of anti-inflammatory and mucus-regulatory activities of a fixed combination of thyme and primula extracts. Pulm Pharmacol Ther. 2018;51:10-7.
33. Seibel J, Wonnemann M, Werz O, Lehner MD. A tiered approach to investigate the mechanism of anti-inflammatory activity of an herbal medicinal product containing a fixed combination of thyme herb and primula root extracts. Clin Phytosci. 2018;4(1):4.
34. Cho DY, Skinner D, Mackey C, et al. Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2019;9(6):629-37.
35. Rossi A, Dehm F, Kiesselbach C, et al. The novel Sinupret® dry extract exhibits anti-inflammatory effectiveness in vivo. Fitoterapia. 2012;83(4):715-20.
36. Kreindler JL, Chen B, Kreitman Y, et al. The novel dry extract BNO 1011 stimulates chloride transport and ciliary beat frequency in human respiratory epithelial cultures. Am J Rhinol Allergy. 2012;26(6):439-43.
37. Zupanets IA, Shebeko SK, Popovych VI, Zimin SM. Study of the anti-inflammatory effect of the combined extract BNO 1016 in a leukotriene-dependent in vivo inflammation model. Clin Phytosci. 2020;6(1):7.
38. Kemmerich B, Eberhardt R, Stammer H. Efficacy and tolerability of a fluid extract combination of thyme herb and ivy leaves and matched placebo in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled clinical trial. Arzneimittelforschung. 2006;56(9):652-60.
39. EMA. Committee on Herbal Medicinal Products (HMPC) Assessment report on Matricaria recutita L., flos and Matricaria recutita L., aetheroleum. 7 July 2015. EMA/HMPC/55837/2011 2015 [3 Dec 2020]. Available at: https://www.ema.europa.eu/en/documents/herbal-
report/final-assessment-report-matricaria-recutita-l-flos-matricaria-recutita-l-aetheroleum_en.pdf.Accessed: 01.06.2021.
Авторы
Микела Луиза Де Пеллегрин1, Анетт Рорхофер2, Филипп Шустер1, Барбара Шмидт1,2, Филипп Петербурс*3, Андре Гесснер1,2
1 Институт клинической микробиологии и гигиены, Университетская больница Регенсбурга, Регенсбург, Германия;
2 Институт медицинской микробиологии и гигиены, Университет Регенсбурга, Регенсбург, Германия;
3 «Бионорика СЕ», Ноймаркт, Германия
*Philipp.Peterburs@bionorica.de
1 Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany;
2 Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany;
3 Bionorica SE, Kerschensteinerstraße 11–15, 92318 Neumarkt, Germany
*Philipp.Peterburs@bionorica.de
1 Институт клинической микробиологии и гигиены, Университетская больница Регенсбурга, Регенсбург, Германия;
2 Институт медицинской микробиологии и гигиены, Университет Регенсбурга, Регенсбург, Германия;
3 «Бионорика СЕ», Ноймаркт, Германия
*Philipp.Peterburs@bionorica.de
________________________________________________
1 Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany;
2 Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany;
3 Bionorica SE, Kerschensteinerstraße 11–15, 92318 Neumarkt, Germany
*Philipp.Peterburs@bionorica.de
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