Tiano Sofia Maria Luigia, Landi Nicola, Marano Valentina, Ragucci Sara, Bianco Gennaro, Cacchiarelli Davide, Swuec Paolo, Silva Malan, De Cegli Rossella, Sacco Francesca, Di Maro Antimo, Cortese Mirko
Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy; Scuola Superiore Meridionale (SSM, School of Advanced Studies), Genomics and Experimental Medicine Program, Naples, Italy.
Institute of Crystallography, National Research Council, Caserta, Italy; Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Caserta, Italy.
Int J Biol Macromol. 2024 Sep 15;280(Pt 1):135700. doi: 10.1016/j.ijbiomac.2024.135700.
SARS-CoV-2 pandemic clearly demonstrated the lack of preparation against novel and emerging viral diseases. This prompted an enormous effort to identify antivirals to curb viral spread and counteract future pandemics. Ribosome Inactivating Proteins (RIPs) and Ribotoxin-Like Proteins (RL-Ps) are toxin enzymes isolated from edible plants and mushrooms, both able to inactivate protein biosynthesis. In the present study, we combined imaging analyses, transcriptomic and proteomic profiling to deeper investigate the spectrum of antiviral activity of quinoin, type 1 RIP from quinoa seeds. Here, we show that RIPs, but not RL-Ps, act on a post-entry step and impair SARS-CoV-2 replication, potentially by direct degradation of viral RNA. Interestingly, the inhibitory activity of quinoin was conserved also against other members of the Coronaviridae family suggesting a broader antiviral effect. The integration of mass spectrometry (MS)-based proteomics with transcriptomics, provided a comprehensive picture of the quinoin dependent remodeling of crucial biological processes, highlighting an unexpected impact on lipid metabolism. Thus, direct and indirect mechanisms can contribute to the inhibitory mechanism of quinoin, making RIPs family a promising candidate not only for their antiviral activity, but also as an effective tool to better understand the cellular functions and factors required during SARS-CoV-2 replication.
2019冠状病毒病大流行清楚地表明了在应对新型和新出现的病毒性疾病方面缺乏准备。这促使人们付出巨大努力来寻找抗病毒药物，以遏制病毒传播并应对未来的大流行。核糖体失活蛋白（RIPs）和类核糖毒素蛋白（RL-Ps）是从可食用植物和蘑菇中分离出来的毒素酶，二者都能够使蛋白质生物合成失活。在本研究中，我们结合成像分析、转录组学和蛋白质组学分析，以更深入地研究藜麦种子中的1型RIP藜诺因的抗病毒活性谱。在此，我们表明，RIPs而非RL-Ps作用于病毒进入后的步骤并损害2019冠状病毒病的复制，可能是通过直接降解病毒RNA。有趣的是，藜诺因的抑制活性对冠状病毒科的其他成员也具有保守性，这表明其具有更广泛的抗病毒作用。基于质谱（MS）的蛋白质组学与转录组学的整合，提供了藜诺因对关键生物学过程依赖性重塑的全面图景，突出了其对脂质代谢的意外影响。因此，直接和间接机制都可能促成藜诺因产生抑制作用，这使得RIPs家族不仅因其抗病毒活性，而且作为一种有效工具来更好地理解2019冠状病毒病复制过程中所需的细胞功能和因素，成为一个有前景的候选对象。
