T-705 (Favipiravir)

T-705 (Favipiravir) is a broad-spectrum antiviral drug^[1]. T-705 exerts its antiviral effects by selectively inhibiting the RNA-dependent RNA polymerase (RdRp) of RNA viruses^[2]. The catalytic domain of RdRp is highly conserved among a variety of RNA viruses, which endows T-705 with broad-spectrum antiviral activity^[3], including against influenza virus, Ebola virus, Lassa virus, etc^[4].

In vitro, treatment of H9c2 cardiomyoblasts and CCD-1079Sk skin fibroblasts with T-705 (200–400μM) for 24 hours significantly reduced intracellular ATP levels, inhibited the activity of mitochondrial electron transport chain complexes I and V, induced oxidative stress, and caused DNA damage ^[5]. Pre-treatment of IEC-6 intestinal epithelial cells with T-705 (1600mg/L) for 24 hours, followed by stimulation with TNF-α (50ng/mL) and IFN-γ (100ng/mL) for 48 hours, significantly suppressed inflammatory responses and decreased the expression of apoptosis- and necrosis-related proteins, thereby protecting intestinal epithelial cells from inflammatory damage^[6].

In vivo, oral administration of T-705 (150mg/kg) twice daily to mice infected with Bourbon virus (BRBV-STL), starting on day 1 post-infection and continuing for 8 days, significantly reduced weight loss and increased survival rates in mice^[7]. Oral treatment of mice infected with Mayaro virus (MAYV) with T-705 (300mg/kg) for 5 days significantly reduced viral RNA and infectious viral particles in the blood and tissues. T-705 also significantly decreased levels of liver disease markers aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in the blood of MAYV-infected mice^[8].

References:
[1] Shiraki K, Daikoku T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol Ther. 2020 May;209:107512.
[2] Korula P, Alexander H, John JS, et al. Favipiravir for treating COVID-19. Cochrane Database Syst Rev. 2024 Feb 5;2(2):CD015219.
[3] Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463.
[4] Smyk JM, Majewska A. Favipiravir in the Battle with Respiratory Viruses. Mini Rev Med Chem. 2022;22(17):2224-2236.
[5] Gunaydin-Akyildiz A, Aksoy N, Boran T, et al. Favipiravir induces oxidative stress and genotoxicity in cardiac and skin cells. Toxicol Lett. 2022 Dec 1;371:9-16.
[6] Ozgurbuz U, Kabadayi Ensarioglu H, et al. Favipiravir Protects Enterocytes From Cell Death After Inflammatory Storm. Cureus. 2023 Oct 21;15(10):e47417.
[7] Bricker TL, Shafiuddin M, Gounder AP, et al. Therapeutic efficacy of favipiravir against Bourbon virus in mice. PLoS Pathog. 2019 Jun 13;15(6):e1007790.
[8] Bengue M, Pintong AR, Liegeois F, et al. Favipiravir Inhibits Mayaro Virus Infection in Mice. Viruses. 2021 Nov 3;13(11):2213.

T-705 (Favipiravir)是一种广谱抗病毒药物^[1]。T-705通过选择性抑制RNA病毒的RNA依赖性RNA聚合酶（RdRp），发挥抗病毒作用^[2]。由于RdRp的催化结构域在多种RNA病毒中高度保守，使得T-705具有广泛的抗病毒活性^[3]，包括流感病毒、埃博拉病毒、拉沙病毒等^[4]。

在体外，T-705（200–400μM）处理H9c2心肌母细胞和CCD-1079Sk皮肤成纤维细胞24小时，T-705显著降低细胞内ATP含量，抑制线粒体电子传递链复合体I和V的活性，诱导氧化应激，造成DNA损伤^[5]。T-705（1600mg/L）预处理IEC-6肠上皮细胞24小时后，再用TNF-α（50ng/mL）和IFN-γ（100ng/mL）刺激48小时，T-705可显著抑制炎症反应，降低细胞凋亡和坏死相关蛋白的表达，保护肠上皮细胞免受炎症损伤^[6]。

在体内，T-705（150mg/kg）每天两次口服给药，从感染Bourbon病毒（BRBV-STL）的小鼠感染后第1天开始给药，持续8天，T-705显著减轻小鼠体重下降，提高了小鼠的存活率^[7]。T-705（300mg/kg；5天）口服治疗感染马亚罗病毒（MAYV）的小鼠，T-705显著减少了血液和组织中的病毒RNA和感染性病毒颗粒，T-705还显著降低了MAYV感染小鼠血液中肝病标志物天门冬氨酸氨基转移酶（ASAT）和丙氨酸氨基转移酶（ALAT）的水平^[8]。