Quinoin, type 1 ribosome inactivating protein alters SARS-CoV-2 viral replication organelle restricting viral replication and spread.

Autor: Tiano SML; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy; Scuola Superiore Meridionale (SSM, School of Advanced Studies), Genomics and Experimental Medicine Program, Naples, Italy., Landi N; Institute of Crystallography, National Research Council, Caserta, Italy; Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Caserta, Italy., Marano V; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy; PhD Program in Cellular and Molecular Biology, Department of Biology, University of Rome 'Tor Vergata', Rome, Italy., Ragucci S; Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Caserta, Italy., Bianco G; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy., Cacchiarelli D; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy; Scuola Superiore Meridionale (SSM, School of Advanced Studies), Genomics and Experimental Medicine Program, Naples, Italy; Department of Translational Medicine, University of Naples 'Federico II', Naples, Italy., Swuec P; Cryo-Electron Microscopy Unit, National Facility for Structural Biology, Human Technopole, Milan, Italy., Silva M; Cryo-Electron Microscopy Unit, National Facility for Structural Biology, Human Technopole, Milan, Italy., De Cegli R; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy., Sacco F; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy; Department of Biology, University of Rome Tor Vergata, Rome, Italy., Di Maro A; Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Caserta, Italy. Electronic address: antimo.dimaro@unicampania.it., Cortese M; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy; Scuola Superiore Meridionale (SSM, School of Advanced Studies), Genomics and Experimental Medicine Program, Naples, Italy; Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Caserta, Italy. Electronic address: mirko.cortese@unicampania.it.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Sep 15; Vol. 280 (Pt 1), pp. 135700. Date of Electronic Publication: 2024 Sep 15.
DOI: 10.1016/j.ijbiomac.2024.135700
Abstrakt: 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.
Competing Interests: Declaration of competing interest Davide Cacchiarelli is founder, shareholder, and consultant of NEGEDIA S.r.l. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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