Condensates of SARS-CoV-2 Nucleoprotein on Viral RNA and Their Small Molecule Modulators

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Several types of biopolymers undergo liquid-liquid phase separation (form condensates) in aqueous solutions, and this phenomenon has been characterized in detail for 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 analyzed available data on N-protein separation in the presence of viral RNA. Particular attention was paid to transient contacts within the condensates and the N-protein/RNA fragments that form these contacts. We also discussed the presumed role of the condensates in the SARS-CoV-2 life cycle and summarized their influence on the host protective machinery. Finally, we commented on the possibility of regulating the viral condensates using synthetic or native small molecules (phase separation modulators), which can provide a new option in the design of antiviral agents.

作者简介

J. Svetlova

Federal Research and Clinical Center of Physical-Chemical Medicine

Email: annavarizhuk@rcpcm.org
Russia, 119435, Moscow, ul. Malaya Pirogovskaya 1a

Iu. Pavlova

Federal Research and Clinical Center of Physical-Chemical Medicine; Moscow Institute of Physics and Technology

Email: annavarizhuk@rcpcm.org
Russia, 119435, Moscow, ul. Malaya Pirogovskaya 1a; Russia, 141701, Dolgoprudny, Institutskii per. 9

A. Aralov

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: annavarizhuk@rcpcm.org
Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10

A. Varizhuk

Federal Research and Clinical Center of Physical-Chemical Medicine; Moscow Institute of Physics and Technology

Email: annavarizhuk@rcpcm.org
Russia, 119435, Moscow, ul. Malaya Pirogovskaya 1a; Russia, 141701, Dolgoprudny, Institutskii per. 9

参考

  1. Aleem A., Akbar Samad A.B., Slenker A.K. // Emerging Variants of SARS-CoV-2 and Novel Therapeutics Against Coronavirus (COVID-19). In: StatPearls. Treasure Island (FL): StatPearls Publishing, 2022. https://pubmed.ncbi.nlm.nih.gov/34033342/
  2. Huang Y., Yang C., Xu X., Xu W., Liu S. // Acta Pharmacol. Sin. 2020. V. 41. P. 1141–1149. https://doi.org/10.1038/s41401-020-0485-4
  3. Ullrich S., Nitsche C. // Bioorg. Med. Chem. Lett. 2020. V. 30. P. 127377. https://doi.org/10.1016/j.bmcl.2020.127377
  4. Uengwetwanit T., Chutiwitoonchai N., Wichapong K., Karoonuthaisiri N. // Comput. Struct. Biotechnol. J. 2022. V. 20. P. 882–890. https://doi.org/10.1016/j.csbj.2022.02.001
  5. Bai Z., Cao Y., Liu W., Li J. // Viruses. 2022. V. 13. P. 1115. https://doi.org/10.3390/v13061115
  6. Yao H., Song Y., Chen Y., Wu N., Xu J., Sun C., Zhang J., Weng T., Zhang Z., Wu Z., Cheng L., Shi D., Lu X., Lei J., Crispin M., Shi Y., Li L., Li S. // Cell. 2020. V. 183. P. 730–738.E13. https://doi.org/10.1016/j.cell.2020.09.018
  7. Lu S., Ye Q., Singh D., Cao Y., Diedrich J.K., Yates III J.R., Villa E., Cleveland D.W., Corbett K.D. // Nat. Commun. 2021. V. 12. P. 502. https://doi.org/10.1038/s41467-020-20768-y
  8. Cubuk J., Alston J.J., Incicco J.J., Singh S., Stuchell-Brereton M.D., Ward M.D., Zimmerman M.I., Vithani N., Griffith D., Wagoner J.A., Bowman G.R., Hall K.B., Soranno A., Holehouse A.S. // Nat. Commun. 2021. V. 12. P. 1936. https://doi.org/10.1038/s41467-021-21953-3
  9. Wang B., Zhang L., Dai T., Qin Z., Lu H., Zhang L., Zhou F. // Signal Transduct. Target. Ther. 2021. V. 6. P. 290. https://doi.org/10.1038/s41392-021-00678-1
  10. Li H., Ernst C., Kolonko-Adamska M., Man J., Parissi V., Wai-Lung Ng B. // Trends Microbiol. 2022. V. 30. P. 1217–1231. https://doi.org/10.1016/j.tim.2022.06.005
  11. Bäuerlein F.J.B., Fernández-Busnadiego R., Baumeister W. // Trends Cell. Biol. 2020. V. 30. P. 951–966. https://doi.org/10.1016/j.tcb.2020.08.007
  12. Savastano A., Ibáñez de Opakua A., Rankovic M., Zweckstetter M. // Nat. Commun. 2020. V. 11. P. 6041. https://doi.org/10.1038/s41467-020-19843-1
  13. Cascarina S.M., Ross E.D. // FASEB J. 2020. V. 34. P. 9832–9842. https://doi.org/10.1096/fj.202001351
  14. Cascarina S.M., Ross E.D. // J. Biol. Chem. 2022. V. 298. P. 101677. https://doi.org/10.1016/j.jbc.2022.101677
  15. Dang M., Song J. // Biophys. Rev. 2022. V. 14. P. 709–715. https://doi.org/10.1007/s12551-022-00957-3
  16. Alberti S., Gladfelter A., Mittag T. // Cell. 2019. V. 176. P. 419–434. https://doi.org/10.1016/j.cell.2018.12.035
  17. Abyzov A., Blackledge M., Zweckstetter M. // Chem. Rev. 2022. V. 122. P. 6719–6748. https://doi.org/10.1021/acs.chemrev.1c00774
  18. Titus A.R., Ferreira L.A., Belgovskiy A.I., Kooijman E.E., Mann E.K., Mann J.A., Meyer W.V., Smart A.E., Uversky V.N., Zaslavsky B.Y. // Phys. Chem. Chem. Phys. 2020. V. 22. P. 4574–4580. https://doi.org/10.1039/C9CP05810A
  19. Jo Y., Jang J., Song D., Park H., Jung Y. // Chem. Sci. 2022. V. 13. P. 522–530. https://doi.org/10.1039/D1SC05672G
  20. O’Flynn B.G., Mittag T. // Curr. Opin. Cell. Biol. 2021. V. 69. P. 70–79. https://doi.org/10.1016/j.ceb.2020.12.012
  21. Brocca S., Grandori R., Longhi S., Uversky V. // Int. J. Mol. Sci. 2020. V. 21. P. 9045. https://doi.org/10.3390/ijms21239045
  22. Zhou R., Zeng R., von Brunn A., Lei J. // Mol. Biomed. 2020. V. 1. P. 2. https://doi.org/10.1186/s43556-020-00001-4
  23. Wang S., Dai T., Qin Z., Pan T., Chu F., Lou L., Zhang L., Yang B., Huang H., Lu H., Zhou F. // Nat. Cell. Biol. 2021. V. 23. P. 718–732. https://doi.org/10.1038/s41556-021-00710-0
  24. Roden C.A., Dai Y., Giannetti C.A., Seim I., Lee M., Sealfon R., McLaughlin G.A., Boerneke M.A., Iserman C., Wey S.A., Ekena J.L., Troyanskaya O.G., Weeks K.M., You L., Chilkoti A., Gladfelter A.S. // Nucleic Acids Res. 2022. V. 50. P. 8168–8192. https://doi.org/10.1093/nar/gkac596
  25. Iserman C., Roden C.A., Boerneke M.A., Sealfon R.S.G., McLaughlin G.A., Jungreis I., Fritch E.J., Hou Y.J., Ekena J., Weidmann C.A., Theesfeld C.L., Kellis M., Troyanskaya O.G., Baric R.S., Sheahan T.P., Weeks K.M., Gladfelter A.S. // Mol. Cell. 2020. V. 80. P. 1078–1091.E6. https://doi.org/10.1016/j.molcel.2020.11.041
  26. Riback J.A., Zhu L., Ferrolino M.C., Tolbert M., Mitrea D.M., Sanders D.W., Wei M.-T., Kriwacki R.W., Brangwynne C.P. // Nature. 2020. V. 581. P. 209–214. https://doi.org/10.1038/s41586-020-2256-2
  27. Weidmann C.A., Mustoe A.M., Jariwala P.B., Calabrese J.M., Weeks K.M. // Nat. Biotechnol. 2021. V. 39. P. 347–356. https://doi.org/10.1038/s41587-020-0709-7
  28. Zachrdla M., Savastano A., Ibáñez de Opakua A., Cima-Omori M.S., Zweckstetter M. // Protein Sci. 2022. V. 31. P. e4409. https://doi.org/10.1002/pro.4409
  29. Banani S.F., Rice A.M., Peeples W.B., Lin Y., Jain S., Parker R., Rosen M.K. // Cell. 2016. V. 166. P. 651–663. https://doi.org/10.1016/j.cell.2016.06.010
  30. Choi J.-M., Holehouse A.S., Pappu R.V. // Annu. Rev. Biophys. 2020. V. 49. P. 107–133. https://doi.org/10.1146/annurev-biophys-121219-081629
  31. Lin Y.-H., Brady J.P., Chan H.S., Ghosh K. // J. Chem. Phys. 2020. V. 152. P. 045102. https://doi.org/10.1063/1.5139661
  32. Supekar N.T., Shajahan A., Gleinich A.S., Rouhani D.S., Heiss C., Chapla D.G., Moremen K.W., Azadi P. // Glycobiology. 2021. V. 31. P. 1080–1092. https://doi.org/10.1093/glycob/cwab044
  33. Wu J., Zhong Y., Liu X., Lu X., Zeng W., Wu C., Xing F., Cao L., Zheng F., Hou P., Peng H., Li C., Guo D. // J. Mol. Cell. Biol. 2022. V. 14. P. mjac003. https://doi.org/10.1093/jmcb/mjac003
  34. Wang J., Choi J.-M., Holehouse A.S., Lee H.O., Zhang X., Jahnel M., Maharana S., Lemaitre R., Pozniakovsky A., Drechsel D., Poser I., Pappu R.V., Alberti S., Hyman A.A. // Cell. 2018. V. 174. P. 688–699.E16. https://doi.org/10.1016/j.cell.2018.06.006
  35. Vernon R.M., Chong P.A., Tsang B., Kim T.H., Bah A., Farber P., Lin H., Forman-Kay J.D. // eLife. 2018. V. 7. P. e31486. https://doi.org/10.7554/eLife.31486
  36. Caruso I.P., dos Santos Almeida V., do Amaral M.J., de Andrade G.C., de Araújo G.R., de Araújo T.S., de Azevedo J.M., Barbosa G.M., Bartkevihi L., Bezerra P.R., dos Santos Cabral K.M., de Lourenço I.O., Malizia-Motta C.L.F., de Luna Marques A., Mebus-Antunes N.C., Neves-Martins T.C., de Sá J.M., Sanches K., Santana-Silva M.C., Vasconcelos A.A., da Silva Almeida M., de Amorim G.C., Anobom C.D., da Poian A.T., Gomes-Neto F., Pinheiro A.S., Almeida F.C.L. // Int. J. Biol. Macromol. 2022. V. 203. P. 466–480. https://doi.org/10.1016/j.ijbiomac.2022.01.121
  37. Zhao H., Nguyen A., Wu D., Li Y., Hassan S.A., Chen J., Shroff H., Piszczek G., Schuck P. // PNAS Nexus. 2022. V. 1. P. pgac049. https://doi.org/10.1093/pnasnexus/pgac049
  38. Bogunia M., Makowski M. // J. Phys. Chem. B. 2020. V. 124. P. 10326–10336. https://doi.org/10.1021/acs.jpcb.0c06399
  39. Gao T., Gao Y., Liu X., Nie Z., Sun H., Lin K., Peng H., Wang S. // BMC Microbiol. 2021. V. 21. P. 58. https://doi.org/10.1186/s12866-021-02107-3
  40. Dang M., Li Y., Song J. // Biochem. Biophys. Res. Commun. 2021. V. 541. P. 50–55. https://doi.org/10.1016/j.bbrc.2021.01.018
  41. Kim D., Lee J.-Y., Yang J.-S., Kim J.W., Kim V.N., Chang H. // Cell. 2020. V. 181. P. 914–921.E10. https://doi.org/10.1016/j.cell.2020.04.011
  42. Malone B., Urakova N., Snijder E.J., Campbell E.A. // Nat. Rev. Mol. Cell Biol. 2022. V. 23. P. 21–39. https://doi.org/10.1038/s41580-021-00432-z
  43. Ziv O., Price J., Shalamova L., Kamenova T., Goodfellow I., Weber F., Miska E.A. // Mol. Cell. 2022. V. 80. P. 1067–1077.E5. https://doi.org/10.1016/j.molcel.2020.11.004
  44. Klein S., Cortese M., Winter S.L., Wachsmuth-Melm M., Neufeldt C.J., Cerikan B., Stanifer M.L., Boulant S., Bartenschlager R., Chlanda P. // Nat. Commun. 2020. V. 11. P. 5885. https://doi.org/10.1038/s41467-020-19619-7
  45. Zhang Z., Nomura N., Muramoto Y., Ekimoto T., Uemura T., Liu K., Yui M., Kono N., Aoki J., Ikeguchi M., Noda T., Iwata S., Ohto U., Shimizu T. // Nat. Commun. 2022. V. 13. P. 4399. https://doi.org/10.1038/s41467-022-32019-3
  46. Perdikari T.M., Murthy A.C., Ryan V.H., Watters S., Naik M.T., Fawzi N.L. // EMBO J. 2020. V. 39. P. e106478. https://doi.org/10.15252/embj.2020106478
  47. Luo L., Li Z., Zhao T., Ju X., Ma P., Jin B., Zhou Y., He S., Huang J., Xu X., Zou Y., Li P., Liang A., Liu J., Chi T., Huang X., Ding Q., Jin Z., Huang C., Zhang Y. // Sci. Bull. (Beijing). 2021. V. 66. P. 1194–1204. https://doi.org/10.1016/j.scib.2021.01.013
  48. Wang W., Chen J., Yu X., Lan H.Y. // Int. J. Biol. Sci. 2022. V. 18. P. 4704–4713. https://doi.org/10.7150/ijbs.72663
  49. Oh S.J., Shin O.S. // Cells. 2021. V. 10. P 530. https://doi.org/10.3390/cells10030530
  50. Wu Y., Ma L., Cai S., Zhuang Z., Zhao Z., Jin S., Xie W., Zhou L., Zhang L., Zhao J., Cui J. // Signal Transduct. Target. Ther. 2021. V. 6. P. 167. https://doi.org/10.1038/s41392-021-00575-7
  51. Tay M.Z., Poh C.M., Rénia L., MacAry P.A., Ng L.F.P. // Nat. Rev. Immunol. 2020. V. 20. P. 363–374. https://doi.org/10.1038/s41577-020-0311-8
  52. Dang M., Song J. // Protein Sci. 2022. V. 31. P. 345–356. https://doi.org/10.1002/pro.4221
  53. Patel A., Malinovska L., Saha S., Wang J., Alberti S., Krishnan Y., Hyman A.A. // Science. 2017. V. 356. P. 753–756. https://doi.org/10.1126/science.aaf6846
  54. Song J. // Protein Sci. 2021. V. 30. P. 1277–1293. https://doi.org/10.1002/pro.4079
  55. Kang J., Lim L., Lu Y., Song J. // PLoS Biol. 2019. V. 17. P. 1–33. https://doi.org/10.1371/journal.pbio.3000327
  56. Dinesh D.C., Chalupska D., Silhan J., Koutna E., Nencka R., Veverka V., Boura E. // PLoS Pathog. 2020. V. 16. P. 1–16. https://doi.org/10.1371/journal.ppat.1009100
  57. Zhao D., Xu W., Zhang X., Wang X., Ge Y., Yuan E., Xiong Y., Wu S., Li S., Wu N., Tian T., Feng X., Shu H., Lang P., Li J., Zhu F., Shen X., Li H., Li P., Zeng J. // Protein Cell. 2021. V. 12. P. 734–740. https://doi.org/10.1007/s13238-021-00832-z
  58. Zhao M., Yu Y., Sun L.-M., Xing J.-Q., Li T., Zhu Y., Wang M., Yu Y., Xue W., Xia T., Cai H., Han Q.-Y., Yin X., Li W.-H., Li A.-L., Cui J., Yuan Z., Zhang R., Zhou T., Zhang X.-M., Li T. // Nat. Commun. 2021. V. 12. P. 2114. https://doi.org/10.1038/s41467-021-22297-8
  59. Gorąca A., Huk-Kolega H., Piechota A., Kleniewska P., Ciejka E., Skibska B. // Pharmacol. Rep. 2011. V. 63. P. 849–858. https://doi.org/10.1016/S1734-1140(11)70600-4
  60. Gordon D.E., Jang G.M., Bouhaddou M., Xu J., Obernier K., White K.M., O’Meara M.J., Rezelj V.V., Guo J.Z., Swaney D.L., Tummino T.A., Hüttenhain R., Kaake R.M., Richards A.L., Tutuncuoglu B., Foussard H., Batra J., Haas K., Modak M., Kim M., Haas P., Polacco B.J., Braberg H., Fabius J.M., Eckhardt M., Soucheray M., Bennett M.J., Cakir M., McGregor M.J., Li Q., Meyer B., Roesch F., Vallet T., Mac Kain A., Miorin L., Moreno E., Naing Z.Z.C., Zhou Y., Peng S., Shi Y., Zhang Z., Shen W., Kirby I.T., Melnyk J.E., Chorba J.S., Lou K., Dai S.A., Barrio-Hernandez I., Memon D., Hernandez-Armenta C., Lyu J., Mathy C.J.P., Perica T., Pilla K.B., Ganesan S.J., Saltzberg D.J., Rakesh R., Liu X., Rosenthal S.B., Calviello L., Venkataramanan S., Liboy-Lugo J., Lin Y., Huang X.P., Liu Y., Wankowicz S.A., Bohn M., Safari M., Ugur F.S., Koh C., Savar N.S., Tran Q.D., Shengjuler D., Fletcher S.J., O’Neal M.C., Cai Y., Chang J.C.J., Broadhurst D.J., Klippsten S., Sharp P.P., Wenzell N.A., Kuzuoglu-Ozturk D., Wang H.Y., Trenker R., Young J.M., Cavero D.A., Hiatt J., Roth T.L., Rathore U., Subramanian A., Noack J., Hubert M., Stroud R.M., Frankel A.D., Rosenberg O.S., Verba K.A., Agard D.A., Ott M., Emerman M., Jura N., von Zastrow M., Verdin E., Ashworth A., Schwartz O., d’Enfert C., Mukherjee S., Jacobson M., Malik H.S., Fujimori D.G., Ideker T., Craik C.S., Floor S.N., Fraser J.S., Gross J.D., Sali A., Roth B.L., Ruggero D., Taunton J., Kortemme T., Beltrao P., Vignuzzi M., García-Sastre A., Shokat K.M., Shoichet B.K., Krogan N.J. // Nature. 2020. V. 583. P. 459–468. https://doi.org/10.1038/s41586-020-2286-9
  61. Wheeler R.J., Lee H.O., Poser I., Pal A., Doeleman T., Kishigami S., Kour S., Anderson E.N., Marrone L., Murthy A.C., Jahnel M., Zhang X., Boczek E., Fritsch A., Fawzi N.L., Sterneckert J., Pandey U., David D.C., Davis B.G., Baldwin A.J., Hermann A., Bickle M., Alberti S., Hyman A.A. // bioRxiv. 2019. https://doi.org/10.1101/721001
  62. Itoh Y., Iida S., Tamura S., Nagashima R., Shiraki K., Goto T., Hibino K., Ide S., Maeshima K. // Life Sci. Alliance. 2021. V. 4. P. e202001005. https://doi.org/10.26508/lsa.202001005
  63. Blount K.F., Zhao F., Hermann T., Tor Y. // J. Am. Chem. Soc. 2005. V. 127. P. 9818–9829. https://doi.org/10.1021/ja050918w
  64. Svetlova J., Knizhnik E., Manuvera V., Severov V., Shirokov D., Grafskaia E., Bobrovsky P., Matyugina E., Khandazhinskaya A., Kozlovskaya L., Miropolskaya N., Aralov A., Khodarovich Y., Tsvetkov V., Kochetkov S., Lazarev V., Varizhuk A. // Int. J. Mol. Sci. 2022. V. 23. P. 15281. https://doi.org/10.3390/ijms232315281

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