Jung Su-Bin, Choi Grace, Kim Hyo-Jin, Moon Kyeong-Seo, Lee Gun, Na Kyeong-Hak, Kwon Yong Min, Moon Jimin, Shin Mi Yeong, Yu Jae-Yeong, Baek Yeong-Bin, Park Jun-Gyu, Park Sang-Ik
Department of Veterinary Pathology, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Republic of Korea.
Department of Biological Application and Technology, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea.
Microorganisms. 2024 Mar 28;12(4):677. doi: 10.3390/microorganisms12040677.
Epidemic diseases that arise from infectious RNA viruses, particularly influenza viruses, pose a constant threat to the global economy and public health. Viral evolution has undermined the efficacy of acquired immunity from vaccines and the antiviral effects of FDA-approved drugs. As such, there is an urgent need to develop new antiviral lead agents. Natural compounds, owing to their historical validation of application and safety, have become a promising solution. In this light, a novel marine bacterium, sp. M20A4R8, has been found to exhibit significant antiviral activity [half maximal inhibitory concentration (IC) = 1.3 µg/mL, selectivity index (SI) = 919.4] against influenza virus A/Puerto Rico/8/34, surpassing the activity of chloroquine. The antiviral response via M20A4R8 extract was induced during post-entry stages of the influenza virus, indicating suitability for post-application after the establishment of viral infection. Furthermore, post-treatment with M20A4R8 extract protected the host from virus-induced apoptosis, suggesting its potential use in acute respiratory disease complexes resulting from immune effectors' overstimulation and autophagy-mediated self-apoptosis. The extract demonstrated an outstanding therapeutic index against influenza virus A/Wisconsin/15/2009 (IC = 8.1 µg/mL, SI = 146.2) and B/Florida/78/2015 Victoria lineage (IC = 3.5 µg/mL, SI = 343.8), indicating a broad anti-influenza virus activity with guaranteed safety and effectiveness. This study provides a new perspective on mechanisms for preventing a broad spectrum of viral infections through antiviral agents from novel and natural origins. Future studies on a single or combined compound from the extract hold promise, encouraging its use in preclinical challenge tests with various influenza virus strains.
由传染性RNA病毒,特别是流感病毒引起的流行病,对全球经济和公共卫生构成持续威胁。病毒进化削弱了疫苗获得性免疫的效力以及美国食品药品监督管理局(FDA)批准药物的抗病毒效果。因此,迫切需要开发新的抗病毒先导药物。天然化合物由于其应用和安全性的历史验证,已成为一种有前景的解决方案。有鉴于此,已发现一种新型海洋细菌,即sp. M20A4R8,对甲型流感病毒A/波多黎各/8/34表现出显著的抗病毒活性[半数最大抑制浓度(IC)= 1.3微克/毫升,选择性指数(SI)= 919.4],超过了氯喹的活性。通过M20A4R8提取物产生的抗病毒反应是在流感病毒进入后的阶段诱导的,表明其适用于病毒感染确立后的后期应用。此外,用M20A4R8提取物进行后期治疗可保护宿主免受病毒诱导的凋亡,表明其在免疫效应器过度刺激和自噬介导的自我凋亡导致的急性呼吸道疾病复合体中的潜在用途。该提取物对甲型流感病毒A/威斯康星/15/2009(IC = 8.1微克/毫升,SI = 146.2)和乙型流感病毒B/佛罗里达/78/2015维多利亚系(IC = 3.5微克/毫升,SI = 343.8)表现出出色的治疗指数,表明具有广泛的抗流感病毒活性且安全性和有效性有保障。本研究为通过新型天然来源的抗病毒药物预防广泛病毒感染的机制提供了新视角。对提取物中单一或组合化合物的未来研究前景广阔,有望鼓励其用于针对各种流感病毒株的临床前挑战试验。