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Condensates of SARS-CoV-2 Nucleoprotein on Viral RNA and Their Small Molecule Modulators (A Review)

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Abstract

The liquid−liquid phase separation phase separation phenomenon has been described for some biopolymers and has been studied in sufficient detail for a few proteins with intrinsically disordered regions. One example of such proteins is the nucleocapsid (N) protein of the severe acute respiratory syndrome coronavirus 2. In this review, we have analyzed available data on N-protein separation in the presence of viral RNA. Particular attention has been paid to transient contacts within the condensates and the N-protein/RNA fragments that form these contacts. The modern concepts of the role of the condensates in the SARS-CoV-2 life cycle and their influence on the host-protective machinery have been summarized. Finally, comments on the possibility of regulating the viral condensates using synthetic or natural small molecules (phase separation modulators), which can provide a new option in the design of antiviral agents, are given.

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Funding

The research was financially supported by the President of the Russian Federation (grant no. MD-5000.2022.3) and the Ministry of Science and Higher Education of the Russian Federation (agreement no. 075-15-2021-1049).

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Authors and Affiliations

  1. Federal Research and Clinical Center of Physical-Chemical Medicine, 119435, Moscow, Russia

    Yu. I. Svetlova, Yu. I. Pavlova & A. M. Varizhuk

  2. Moscow Institute of Physics and Technology, 141701, Dolgoprudnyi, Russia

    Yu. I. Pavlova & A. M. Varizhuk

  3. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia

    A. V. Aralov

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  1. Yu. I. Svetlova
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Abbreviations: COVID-19, coronavirus disease 2019; CVL218, 5 5-fluoro-2-{4-[(methylamino)methyl]phenyl}-benzofuran-7-carboxamide (Mefuparib); D, dimerization domain; G3BP1/2, Ras-specific GTPase-activating proteins; EC50, half maximal effective concentration; EGCG, epigallocatechin-3-gallate; GCG, gallocatechin-3-gallate; IDR, intrinsically disordered regions; LCT, low critical temperature; LLPS, liquid−liquid phase separation; MAVS, mitochondrial antiviral sensor; PJ34, N-(6-Oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino)acetamide; RBD1, N-terminal RNA-binding domain 1; RBD2, RNA-binding domain 2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SR, serine- and arginine-rich segment; TRS, transcription-regulating signal.

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Svetlova, Y.I., Pavlova, Y.I., Aralov, A.V. et al. Condensates of SARS-CoV-2 Nucleoprotein on Viral RNA and Their Small Molecule Modulators (A Review). Russ J Bioorg Chem 49, 917–929 (2023). https://doi.org/10.1134/S1068162023050229

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  • DOI: https://doi.org/10.1134/S1068162023050229

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