Suramin Disturbs the Association of the N-Terminal Domain of SARS-CoV-2 Nucleocapsid Protein with RNA

Suramin was originally used as an antiparasitic drug in clinics. Here, we demonstrate that suramin can bind to the N-terminal domain of SARS-CoV-2 nucleocapsid protein (N-NTD) and disturb its interaction with RNA. The BLI experiments showed that N-NTD interacts suramin with a dissociate constant (Kd = 2.74 μM) stronger than that of N-NTD with ssRNA-16 (Kd = 8.37 μM). Furthermore, both NMR titration experiments and molecular docking analysis suggested that suramin mainly binds to the positively charged cavity between the finger and the palm subdomains of N-NTD, and residues R88, R92, R93, I94, R95, K102 and A156 are crucial for N-NTD capturing suramin. Besides, NMR dynamics experiments showed that suramin-bound N-NTD adopts a more rigid structure, and the loop between β2-β3 exhibits fast motion on the ps-ns timescale, potentially facilitating suramin binding. Our findings not only reveal the molecular basis of suramin disturbing the association of SARS-CoV-2 N-NTD with RNA but also provide valuable structural information for the development of drugs against SARS-CoV-2.

• Publication year

  2023

• Venue

  Molecules

• Publication date

  2023-03-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.3390/molecules28062534PMID 36985506PMCID 10051649
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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