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BETAFERON'UN COVID-19 İÇİN ANTİVİRAL AKTİVİTESİ

Yıl 2022, , 883 - 895, 30.09.2022
https://doi.org/10.33483/jfpau.1112165

Öz

Amaç: COVID-19 enfeksiyonu 2019'dan beri dünya çapında yayılmış ve pandemik enfeksiyon olarak ilan edilmiştir. Maalesef, insanlık hala bu enfeksiyonla başa çıkmaya çalışıyor. Bu koşullar altında bilim insanları, SARS-CoV-2 viral enfeksiyonu ile mücadelede en hızlı çözüm olarak ilaç yeniden konumlandırma çalışmalarına yönelmiştir. Betaferon (İnterferon beta-1b), interferon ailesinin bir üyesidir ve immün sistem tarafından doğal olarak üretilen interferon beta-1a aynı etki mekanizmasına sahiptir.
Gereç ve Yöntem: Betaferon’un SARS-CoV-2 enfeksiyonuna karşı antiviral etkisi in vitro ve in siliko olarak araştırıldı. Antiviral aktivitenin tayini için ilaç toksisitesi, gen ifadesi ve docking (kenetlenme) hesaplamaları yapılarak değerlendirildi.
Sonuç ve Tartışma: Betaferon, SARS-CoV-2 viral enfeksiyonuna karşı önemli antiviral aktivite göstermiştir. Ayrıca Betaferon, hem virüsün girişinde rol oynayan ACE2 ve TMRPSS2 proteinlerinin ifadesini azaltmıştır. Betaferon, yalnızca TMPRSS2 ifadesini değil, aynı zamanda TMPRSS2'nin proteolitik aktivitesini de doza bağlı bir şekilde azaltmıştır. Bununla birlikte Betaferon'un viral Spike protein ile etkileşime girdiği in silico analizlerle gösterilmiştir. Dolayısıyla, ACE2 ve TMPRSS2 ifadesinin azalması, TMPRSS2 aktivitesinin düşmesi ve SARS-CoV-2'nin Spike proteini ile etkileşimi, Betaferon'un viral giriş yolağını engellenmesi yoluyla SARS-CoV-2 virüsüne karşı antiviral aktiviteye sahip olduğunu göstermiştir.

Kaynakça

  • Merad, M., Blish, C.A., Sallusto, F., Iwasaki, A. (2022). The immunology and immunopathology of COVID-19. Science, 375(6585), 1122–1127. [CrossRef]
  • 2. Lythgoe, M.P., Middleton, P. (2020). Ongoing clinical trials for the management of the COVID-19 pandemic. Trends in Pharmacological Sciences, 41(6), 363–382. [CrossRef]
  • 3. Casaos, J., Gorelick, N.L., Huq, S., Choi, J., Xia, Y., Serra, R., Felder, R., Lott, T., Kast, R.E., Suk, I., Brem, H., Tyler, B., Skuli, N. (2019). The use of ribavirin as an anticancer therapeutic: Will it go viral? Ribavirin as an anticancer therapeutic. Molecular Cancer Therapy, 18(7), 1185–1194. [CrossRef]
  • 4. Burks, J. (2005). Interferon-beta1b for multiple sclerosis. Expert Review of Neurotherapeutic, 5(2), 153–164. [CrossRef]
  • 5. Kieseier, B.C. (2011). The mechanism of action of interferon-β in relapsing multiple sclerosis. CNS Drugs, 25(6), 491–502. [CrossRef]
  • 6. Brzoska, J., Eick, H.V., Hündgen M. (2020). Interferons in the therapy of severe coronavirus infections: A critical analysis and recollection of a forgotten therapeutic regimen with interferon beta. Drug Research, 70(7), 291. [CrossRef]
  • 7. Haile, L.A., Polumuri, S.K., Rao, R., Kelley-Baker, L., Kryndushkin, D., Rajaiah, R., Israely, T., Rao, V.A., Verthelyi, D. (2017). Cell based assay identifies TLR2 and TLR4 stimulating impurities in Interferon beta. Scientific Reports, 7, 10490. [CrossRef]
  • 8. Runkel, L., Meier, W., Pepinsky, R.B., Karpusas, M., Whitty, A., Kimball, K., Brickelmaier, M., Muldowney, C., Jones, W., Goelz, S.E. (1998). Structural and functional differences between glycosylated and non-glycosylated forms of human interferon-β (IFN-β). Pharmaceutical Research, 15(4), 641–649. [CrossRef]
  • 9. Dhib-Jalbut, S. (2002). Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis. Neurology, 58(8), 3-9. [CrossRef]
  • 10. Hensley, L.E., Fritz, E.A., Jahrling, P.B., Karp, C., Huggins, J.W., Geisbert, T.W. (2004). Interferon-β 1a and SARS Coronavirus Replication. Emerging Infectious. Disease, 10(2), 317. [CrossRef]
  • 11. Luckhardt, T.R., Coomes, S.M., Trujillo, G., Stoolman, J.S., Vannella, K.M., Bhan, U., Wilke, C.A., Moore, T.A., Toews, G.B., Hogaboam, C., Moore, B.B. (2011). TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis. Fibrogenesis & Tissue Repair, 4(1), 1–15. [CrossRef]
  • 12. Chu, H., Chan, J.F.W., Wang, Y., Yuen, T.T.T., Chai, Y., Hou, Y., Shuai, H., Yang, D., Hu, B., Huang, X., Zhang, X., Cai, J.P., Zhou, J., Yuan, S., Kok, K.H., To, K. K.W., Chan, I.H.Y., Zhang, A.J., Sit, K.Y., Au, W.-K., Yuen, K.Y. (2020). Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: An ex vivo study with implications for the pathogenesis of COVID-19. Clinical Infectious Disease, 71(6), 1400–1409. [CrossRef]
  • 13. Hung, I.F.N., Lung, K.C., Tso, E.Y.K., Liu, R., Chung, T.W.H., Chu, M.Y., Ng, Y.Y., Lo, J., Chan, J., Tam, A.R., Shum, H.P., Chan, V., Wu, A.K.L., Sin, K.M., Leung, W.S., Law, W.L., Lung, D.C., Sin, S. (2020). Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet, 395(10238), 1695–1704.[CrossRef]
  • 14. Yan, Y., Zhang, D., Zhou, P., Li, B., Huang, S.Y. (2017). HDOCK: a web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy. Nucleic Acids Research, 3(45), 365-373. [CrossRef]
  • 15. BIOVIA Discovery Studio 2017. Dassault Systèmes, San Diego, California, USA. Available from http://www.3ds.com/products-services/biovia/.
  • 16. Unal, M.A., Bitirim, C.V., Summak, G.Y., Bereketoglu, S., Zeytin, I.C., Besbinar, O., Gurcan, C., Aydos, D., Goksoy, E., Kocakaya, E., Eran, Zeynep., Murat, M., Demir, N., Aksoy Ozer, Z. B., Somers, J., Demir, E., Nazir, H., Ozkan, S.A., Ozkul, A., Azap, A., Yilmazer, A., Akcali, K.C. (2021). Ribavirin shows antiviral activity against sars-cov-2 and downregulates the activity of tmprss2 and the expression of ace2 in vitro. Canadian Journal of Physiology and Pharmacology, 99(5), 449–460. [CrossRef]
  • 17. Ko, C.J., Huang, C.C., Lin, H.Y., Juan, C.P., Lan, S.W., Shyu, H.Yi., Wu, S.R., Hsiao, P.W., Huang, H.P., Shun, C.T., Lee, M.S. (2015). Androgen-induced TMPRSS2 activates matriptase and promotes extracellular matrix degradation, prostate cancer cell invasion, tumor growth, and metastasis. Cancer Research, 75(14), 2949–2960. [CrossRef]

ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19

Yıl 2022, , 883 - 895, 30.09.2022
https://doi.org/10.33483/jfpau.1112165

Öz

Objective: SARS-CoV-2 infection has been spread worldwide since 2019 and declared a pandemic infection. Unfortunately, humanity is still trying to deal with the infection. Under these circumstances, scientists head towards drug repurposing studies as the fastest solution for combatting SARS-CoV-2 viral infection. Betaferon (Interferon beta-1b) is a member of interferons, and its mechanism of action is the same as naturally produced interferon beta-1a in the immune system.
Material and Method: In this study, the antiviral effect of Betaferon on SARS-CoV-2 infection in vitro and in silico was analyzed. The drug toxicity, gene expression, and docking calculations are evaluated.
Result and Discussion: Betaferon showed significant antiviral activity against COVID-19. Furthermore, Betaferon decreased the expression of both viral entries mediating proteins such as ACE2 and TMRPSS2. Betaferon decreases not only the expression of TMPRSS2 but also the enzymatic activity of TMPRSS2. Furthermore, in silico analyses revealed that Betaferon interacts with viral Spike protein. Hence, a decrease in the expression of viral entry mediating proteins, inhibition of the activity of TMPRSS2, and interaction with viral Spike protein indicate that Betaferon has an antiviral activity for COVID-19 virus through inhibition of viral entry pathway. 

Kaynakça

  • Merad, M., Blish, C.A., Sallusto, F., Iwasaki, A. (2022). The immunology and immunopathology of COVID-19. Science, 375(6585), 1122–1127. [CrossRef]
  • 2. Lythgoe, M.P., Middleton, P. (2020). Ongoing clinical trials for the management of the COVID-19 pandemic. Trends in Pharmacological Sciences, 41(6), 363–382. [CrossRef]
  • 3. Casaos, J., Gorelick, N.L., Huq, S., Choi, J., Xia, Y., Serra, R., Felder, R., Lott, T., Kast, R.E., Suk, I., Brem, H., Tyler, B., Skuli, N. (2019). The use of ribavirin as an anticancer therapeutic: Will it go viral? Ribavirin as an anticancer therapeutic. Molecular Cancer Therapy, 18(7), 1185–1194. [CrossRef]
  • 4. Burks, J. (2005). Interferon-beta1b for multiple sclerosis. Expert Review of Neurotherapeutic, 5(2), 153–164. [CrossRef]
  • 5. Kieseier, B.C. (2011). The mechanism of action of interferon-β in relapsing multiple sclerosis. CNS Drugs, 25(6), 491–502. [CrossRef]
  • 6. Brzoska, J., Eick, H.V., Hündgen M. (2020). Interferons in the therapy of severe coronavirus infections: A critical analysis and recollection of a forgotten therapeutic regimen with interferon beta. Drug Research, 70(7), 291. [CrossRef]
  • 7. Haile, L.A., Polumuri, S.K., Rao, R., Kelley-Baker, L., Kryndushkin, D., Rajaiah, R., Israely, T., Rao, V.A., Verthelyi, D. (2017). Cell based assay identifies TLR2 and TLR4 stimulating impurities in Interferon beta. Scientific Reports, 7, 10490. [CrossRef]
  • 8. Runkel, L., Meier, W., Pepinsky, R.B., Karpusas, M., Whitty, A., Kimball, K., Brickelmaier, M., Muldowney, C., Jones, W., Goelz, S.E. (1998). Structural and functional differences between glycosylated and non-glycosylated forms of human interferon-β (IFN-β). Pharmaceutical Research, 15(4), 641–649. [CrossRef]
  • 9. Dhib-Jalbut, S. (2002). Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis. Neurology, 58(8), 3-9. [CrossRef]
  • 10. Hensley, L.E., Fritz, E.A., Jahrling, P.B., Karp, C., Huggins, J.W., Geisbert, T.W. (2004). Interferon-β 1a and SARS Coronavirus Replication. Emerging Infectious. Disease, 10(2), 317. [CrossRef]
  • 11. Luckhardt, T.R., Coomes, S.M., Trujillo, G., Stoolman, J.S., Vannella, K.M., Bhan, U., Wilke, C.A., Moore, T.A., Toews, G.B., Hogaboam, C., Moore, B.B. (2011). TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis. Fibrogenesis & Tissue Repair, 4(1), 1–15. [CrossRef]
  • 12. Chu, H., Chan, J.F.W., Wang, Y., Yuen, T.T.T., Chai, Y., Hou, Y., Shuai, H., Yang, D., Hu, B., Huang, X., Zhang, X., Cai, J.P., Zhou, J., Yuan, S., Kok, K.H., To, K. K.W., Chan, I.H.Y., Zhang, A.J., Sit, K.Y., Au, W.-K., Yuen, K.Y. (2020). Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: An ex vivo study with implications for the pathogenesis of COVID-19. Clinical Infectious Disease, 71(6), 1400–1409. [CrossRef]
  • 13. Hung, I.F.N., Lung, K.C., Tso, E.Y.K., Liu, R., Chung, T.W.H., Chu, M.Y., Ng, Y.Y., Lo, J., Chan, J., Tam, A.R., Shum, H.P., Chan, V., Wu, A.K.L., Sin, K.M., Leung, W.S., Law, W.L., Lung, D.C., Sin, S. (2020). Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet, 395(10238), 1695–1704.[CrossRef]
  • 14. Yan, Y., Zhang, D., Zhou, P., Li, B., Huang, S.Y. (2017). HDOCK: a web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy. Nucleic Acids Research, 3(45), 365-373. [CrossRef]
  • 15. BIOVIA Discovery Studio 2017. Dassault Systèmes, San Diego, California, USA. Available from http://www.3ds.com/products-services/biovia/.
  • 16. Unal, M.A., Bitirim, C.V., Summak, G.Y., Bereketoglu, S., Zeytin, I.C., Besbinar, O., Gurcan, C., Aydos, D., Goksoy, E., Kocakaya, E., Eran, Zeynep., Murat, M., Demir, N., Aksoy Ozer, Z. B., Somers, J., Demir, E., Nazir, H., Ozkan, S.A., Ozkul, A., Azap, A., Yilmazer, A., Akcali, K.C. (2021). Ribavirin shows antiviral activity against sars-cov-2 and downregulates the activity of tmprss2 and the expression of ace2 in vitro. Canadian Journal of Physiology and Pharmacology, 99(5), 449–460. [CrossRef]
  • 17. Ko, C.J., Huang, C.C., Lin, H.Y., Juan, C.P., Lan, S.W., Shyu, H.Yi., Wu, S.R., Hsiao, P.W., Huang, H.P., Shun, C.T., Lee, M.S. (2015). Androgen-induced TMPRSS2 activates matriptase and promotes extracellular matrix degradation, prostate cancer cell invasion, tumor growth, and metastasis. Cancer Research, 75(14), 2949–2960. [CrossRef]
Toplam 17 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri
Bölüm Araştırma Makalesi
Yazarlar

Fatma Bayrakdar 0000-0001-7531-5080

Sibel A. Özkan 0000-0001-7494-3077

Kamil Can Akçalı Bu kişi benim 0000-0002-7816-6938

Yayımlanma Tarihi 30 Eylül 2022
Gönderilme Tarihi 23 Mayıs 2022
Kabul Tarihi 12 Ağustos 2022
Yayımlandığı Sayı Yıl 2022

Kaynak Göster

APA Bayrakdar, F., Özkan, S. A., & Akçalı, K. C. (2022). ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19. Journal of Faculty of Pharmacy of Ankara University, 46(3), 883-895. https://doi.org/10.33483/jfpau.1112165
AMA Bayrakdar F, Özkan SA, Akçalı KC. ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19. Ankara Ecz. Fak. Derg. Eylül 2022;46(3):883-895. doi:10.33483/jfpau.1112165
Chicago Bayrakdar, Fatma, Sibel A. Özkan, ve Kamil Can Akçalı. “ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19”. Journal of Faculty of Pharmacy of Ankara University 46, sy. 3 (Eylül 2022): 883-95. https://doi.org/10.33483/jfpau.1112165.
EndNote Bayrakdar F, Özkan SA, Akçalı KC (01 Eylül 2022) ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19. Journal of Faculty of Pharmacy of Ankara University 46 3 883–895.
IEEE F. Bayrakdar, S. A. Özkan, ve K. C. Akçalı, “ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19”, Ankara Ecz. Fak. Derg., c. 46, sy. 3, ss. 883–895, 2022, doi: 10.33483/jfpau.1112165.
ISNAD Bayrakdar, Fatma vd. “ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19”. Journal of Faculty of Pharmacy of Ankara University 46/3 (Eylül 2022), 883-895. https://doi.org/10.33483/jfpau.1112165.
JAMA Bayrakdar F, Özkan SA, Akçalı KC. ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19. Ankara Ecz. Fak. Derg. 2022;46:883–895.
MLA Bayrakdar, Fatma vd. “ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19”. Journal of Faculty of Pharmacy of Ankara University, c. 46, sy. 3, 2022, ss. 883-95, doi:10.33483/jfpau.1112165.
Vancouver Bayrakdar F, Özkan SA, Akçalı KC. ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19. Ankara Ecz. Fak. Derg. 2022;46(3):883-95.

Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.