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Discovery and structural characterization of chicoric acid as a SARS-CoV-2 nucleocapsid protein ligand and RNA binding disruptor.

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Mercaldi GF, Bezerra EHS, Batista FAH, Tonoli CCC, Soprano AS, Shimizu JF, Nagai A, da Silva JC, Filho HVR, do Nascimento Faria J, da Cunha MG, Zeri ACM, Nascimento AFZ, Proenca-Modena JL, Bajgelman MC, Rocco SA, Lopes-de-Oliveira PS, Cordeiro AT, Bruder M, Marques RE, Sforça ML, Franchini KG, Benedetti CE, Figueira ACM, Trivella DBB
OpenAccess logo Sci Rep 12 18500 (2022)
Cited: 4 times
EuropePMC logo PMID: 36323732

Abstract

The nucleocapsid (N) protein plays critical roles in coronavirus genome transcription and packaging, representing a key target for the development of novel antivirals, and for which structural information on ligand binding is scarce. We used a novel fluorescence polarization assay to identify small molecules that disrupt the binding of the N protein to a target RNA derived from the SARS-CoV-2 genome packaging signal. Several phenolic compounds, including L-chicoric acid (CA), were identified as high-affinity N-protein ligands. The binding of CA to the N protein was confirmed by isothermal titration calorimetry, 1H-STD and 15N-HSQC NMR, and by the crystal structure of CA bound to the N protein C-terminal domain (CTD), further revealing a new modulatory site in the SARS-CoV-2 N protein. Moreover, CA reduced SARS-CoV-2 replication in cell cultures. These data thus open venues for the development of new antivirals targeting the N protein, an essential and yet underexplored coronavirus target.

Articles - 7uxz mentioned but not cited (1)

  1. Discovery and structural characterization of chicoric acid as a SARS-CoV-2 nucleocapsid protein ligand and RNA binding disruptor. Mercaldi GF, Bezerra EHS, Batista FAH, Tonoli CCC, Soprano AS, Shimizu JF, Nagai A, da Silva JC, Filho HVR, do Nascimento Faria J, da Cunha MG, Zeri ACM, Nascimento AFZ, Proenca-Modena JL, Bajgelman MC, Rocco SA, Lopes-de-Oliveira PS, Cordeiro AT, Bruder M, Marques RE, Sforça ML, Franchini KG, Benedetti CE, Figueira ACM, Trivella DBB. Sci Rep 12 18500 (2022)


Articles citing this publication (3)

  1. Serodominant SARS-CoV-2 Nucleocapsid Peptides Map to Unstructured Protein Regions. Vandervaart JP, Inniss NL, Ling-Hu T, Minasov G, Wiersum G, Rosas-Lemus M, Shuvalova L, Achenbach CJ, Hultquist JF, Satchell KJF, Bachta KER. Microbiol Spectr 11 e0032423 (2023)
  2. ECHOPvir: A Mixture of Echinacea and Hop Extracts Endowed with Cytoprotective, Immunomodulatory and Antiviral Properties. Percaccio E, De Angelis M, Acquaviva A, Nicotra G, Ferrante C, Mazzanti G, Di Giacomo S, Nencioni L, Di Sotto A. Nutrients 15 4380 (2023)
  3. Suramin inhibits SARS-CoV-2 nucleocapsid phosphoprotein genome packaging function. Boniardi I, Corona A, Basquin J, Basquin C, Milia J, Nagy I, Tramontano E, Zinzula L. Virus Res 336 199221 (2023)


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