Shitaye Getasew, Ventserova Nataliia, D'Abrosca Gianluca, Dragone Martina, Maina Eunice Wairimu, Fattorusso Roberto, Iacovino Rosa, Russo Luigi, Isernia Carla, Malgieri Gaetano
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Caserta, Italy.
Department of Biomedical Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia.
Front Chem. 2025 Jun 11;13:1597656. doi: 10.3389/fchem.2025.1597656. eCollection 2025.
Virus survival inside the host cell depends on the intricate mechanisms that recruit proteins involved in the arms race. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) proteome exhibits important levels of structural order. However, some of the SARS-CoV-2 proteins, such as the Nucleocapsid (N) and Non-structural protein 1 (Nsp1), contain a considerably significant amount of intrinsically disordered regions (IDRs) that play indispensable roles in the intra-viral and virus-host interaction. Here, focusing on proteins that contain a relevant percentage of IDRs, we discuss experimental and computational studies sought to support IDRs as a key player in the interplay with ordered domains, the biological role as potential origin for variants of SARS-CoV-2, and their association with virus transmissibility. Furthermore, we also highlight the potential involvement of IDRs in the viral-host protein interaction and host cellular machinery. Thus, shading lights on the dark proteome of the virus and looking for therapeutic approaches beyond the classic structure-function paradigm may contribute to the efforts sparking the quest for therapeutics.
病毒在宿主细胞内的存活取决于招募参与军备竞赛相关蛋白质的复杂机制。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）蛋白质组呈现出重要程度的结构有序性。然而，一些SARS-CoV-2蛋白质，如核衣壳蛋白（N）和非结构蛋白1（Nsp1），含有相当数量的内在无序区域（IDR），这些区域在病毒内以及病毒与宿主的相互作用中发挥着不可或缺的作用。在此，我们聚焦于含有一定比例IDR的蛋白质，讨论实验和计算研究，这些研究旨在支持IDR作为与有序结构域相互作用中的关键因素、作为SARS-CoV-2变体潜在起源的生物学作用以及它们与病毒传播性的关联。此外，我们还强调了IDR在病毒-宿主蛋白质相互作用和宿主细胞机制中的潜在作用。因此，揭示病毒黑暗蛋白质组并寻找超越经典结构-功能范式的治疗方法，可能有助于推动治疗方法的探索。
