Fatma BAYRAKDAR, Sibel A. ÖZKAN, Kamil Can AKÇALI

BETAFERON'UN COVID-19 İÇİN ANTİVİRAL AKTİVİTESİ

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.

Anahtar Kelimeler:

Betaferon, COVID-19, ilaç yeniden konumlandırma, SARS-CoV-2

ANTIVIRAL ACTIVITY OF BETAFERON FOR COVID-19

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.

Keywords:

Betaferon, COVID-19, drug-repurposing, SARS-CoV-2,

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