The effect of favipiravir on interferon related gene expression in human alveolar epithelial cells

Year 2026, Volume: 54 Issue: 1, 37 - 45, 31.12.2025

Kadir Turan , Elif Çağlayan , Pınar Ulupınar , Tuğba Koçmar

https://doi.org/10.15671/hjbc.1743325

Abstract

Favipiravir is a nucleoside analog that is a selective and potent inhibitor of influenza virus RNA-dependent RNA polymerase (RdRp). This drug is considered to be a potential inhibitor of RNA viruses other than influenza due to its effect on the RdRp. In this study, we evaluated the effects of favipiravir on expression of interferon-related genes in alveolar epithelial cells (A549 and BEAS-2B) which produce various types of chemokines. The cytotoxicity and anti-RdRp activity of favipiravir were examined by MTT and virus minireplicon assays, respectively. Favipiravir strongly inhibited human (A/WSN/33-H1N1) and avian type of influenza (A/duck/Pennsylvania-H5N2) virus RdRp at nontoxic doses. The gene transcripts in the cells treated with different doses of favipiravir were analyzed by qPCR and immunoblotting. While CCL2, CAV1 and PRKCZ genes were among the most downregulated genes; IFNB1, IFNE and IL10 genes were the most upregulated in favipiravir-treated cells. The CCL2 and INFB1 transcripts were the most significantly differentiated by favipiravir treatment. The BEAS-2B cells were less sensitive to favipiravir-treatment compared to A549. From this result, it was concluded that favipiravir, while primarily inhibiting the viral RdRp, may also affect cellular interferon defense mechanisms and interfere with virus replication.

Keywords

Favipiravir , interferon , CCL2 , minireplicon

Ethical Statement

No material requiring ethical approval was used in this study. The authors declare that there is no conflict of interest that could be perceived as prejudicial to the impartiality of the reported research.

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Favipiravir'in İnsan Alveolar Epitel Hücrelerinde İnterferonla İlişkili Gen Ekspresyonuna Etkisi

Abstract

Favipiravir, influenza virüsü RNA bağımlı RNA polimerazının (RdRp) seçici ve güçlü inhibitörü olan bir nükleozid analoğudur. Bu ilacın RdRp üzerindeki etkisi nedeniyle influenza dışındaki diğer RNA virüslerinin de potansiyel bir inhibitörü olduğu düşünülmektedir. Bu çalışmada favipiravirin çeşitli kemokinleri üreten alveolar epitel hücrelerinde (A549 ve BEAS-2B) interferon ile ilişkili genlerin ekspresyonuna etkileri değerlendirildi. Favipiravirin sitotoksisitesi MTT testi ile, anti-RdRp aktivitesi ise influenza A virüsü minireplikon modeli ile değerlendirildi. Favipiravir, toksik olmayan dozlarda (200 µg/ml’ye kadar) insan (A/WSN/33-H1N1) ve kuş tipi influenza (A/duck/Pennsylvania-H5N2) virüsü RdRp'yi güçlü bir şekilde inhibe etti. Farklı dozlarda favipiravir ile muamele edilen hücrelerdeki gen transkriptleri kantitatif polimeraz zincir reaksiyonu (qPZR) ve Western melezleme teknikleri ile analiz edildi. Favipiravir etkisinde kalan hücrelerde CCL2, CAV1 ve PRKCZ ekspresyonu en çok azalan genler arasında yer alırken; IFNB1, IFNE ve IL10 ekspresyonu en çok artan genler arasında yer almışlardır. CCL2 ve INFB1 transkriptleri favipiravir etkisi ile en belirgin şekilde farklılaşan genler olmuştur. BEAS-2B hücreleri A549'a kıyasla favipiravire daha az duyarlı bulunmuştur. Elde edilen bu verilerden favipiravirin öncelikle viral RdRp'yi inhibe ettiği, bununla birlikte hücrelerin interferon savunma mekanizmaları aracılığıyla da virüs replikasyonunu etkileyebileceği sonucuna varılmıştır.

Keywords

Favipiravir , interferon , CCL2 , minireplikon

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