NP - Inhibitors

Inhibitors of RNA binding

PMID: 36323732 2022 - Fluorescence polarisation/NMR / RNA binding affinities

(pmid: 26542199)

Similarity of N Cov1 + Cov2

RNA binding domain: 97%; Dimerisation domain: 95%

Conclusion: we should test the Cov1 inhibitors

Targeting RNA binding

(pmid: 25810552) The first strategy is to develop antiviral agents that target the RNA-binding site, which contains a number of conserved residues, and specifically block the formation of RNP during genome replication. For example, naproxen and its derivatives have been proposed to intercalate into the hydrophobic pocket on the RNA-binding groove of influenza virus N protein and inhibit its RNA-binding ability, resulting in reduced viral replication [76,77]. Inhibition of RNP formation by several families of compounds targeting the zinc fingers of HIV N protein has also been demonstrated [43].

Cov1 N structure based approach with validation

(pmid: 26542199) small molecule NSC663284 = H3 table above

Targeting Oligomerisation

(pmid: 25810552) Nucleozin and its derivatives obtained by high-throughput methods have been shown to prevent RNP formation in influenza virus by interfering with N protein oligomerization [78,79]. Similar stratagems can be applied toward development of anticoronaviral agents.