Table 3.
Antivirals and their mechanisms screened by targeting flavivirus two-component NS2B-NS3 proteases.
| Sr No | Flavivirus | Antivirals Screened by Targeting NS2B/NS3 Proteases | Mechanism | Reference |
|---|---|---|---|---|
| 1 | WNV (West Nile Virus) |
Benzoyl-norleucine-lysine-arginine-arginine (Bz-nKRR) tetrapeptide aldehyde | C-terminal electrophile incorporation | [177] |
| Cationic tripeptides (along with nonpeptide cap) | [176] | |||
| Peptide–boronic acid inhibitors | [173] | |||
| Benzyl ethers of 4-hydroxyphenylglycine | N-terminal capping moiety optimization | [172] | ||
| Bz-Arg-Lys-X-NH | [178] | |||
| Peptide-hybrids based on 2,4-thiazolidinedione scaffolds containing nonpolar groups | [179] | |||
| Benzyl ethers of 4-hydroxyphenylglycine | P1 and P2 basic residue modulation | [172] | ||
| Aprotinin | Noncompetitive inhibitors | [117] | ||
| Palmatine (Coptis chinensis) | [180] | |||
| Derivatives of Guanidinylated 2,5-dideoxystreptamine | Competitive inhibitors | [181] | ||
| Benzoyl-norleucine-lysine-arginine- arginine (Bz-nKRR) tetrapeptide aldehyde | Aldehydic inhibitors | [177] | ||
| Cationic tripeptides (along with nonpeptide cap) | [176] | |||
| Aprotinin | Stearic hindrance of active site | [175] | ||
| D-arginine-based 9–12-mer peptides | Mechanism yet to be determined | [175] | ||
| Furin | [182] | |||
| C-Terminal Electrophile incorporation | Peptide–boronic acid inhibitors | [173] | ||
| 2 | DENV (Dengue Virus) |
Tetrapeptide: Bz-Nle-Lys-Arg-Arg-B(OH)2 (boronic acid analogue) |
C-Terminal electrophile incorporation N-terminal capping moiety optimization |
[170] |
| Benzyl ethers of 4-hydroxyphenylglycine | [172] | |||
| Bz-Arg-Lys-X-NH | N-terminal capping moiety optimization P1 and P2 basic residue modulation |
[178] | ||
| Rhodanines and Thiazolidinediones | [183] | |||
| Benzyl ethers of 4-hydroxyphenylglycine | [172] | |||
| Plectasin | Noncompetitive inhibition | [184] | ||
| Substitution of Arg with unnatural Arg motifs in the P2 | P1 and P2 basic residue modulation Aldehydic inhibitors(against DENV 2) |
[185] | ||
| Benzoyl-norleucine-lysine-arginine- arginine (Bz-nKRR) tetrapeptide aldehyde | [177] | |||
| Cationic tripeptides (along with nonpeptide cap) | Aldehydic inhibitors (against DENV 2) | [176] | ||
| Cyclopentapeptide (CKRKC) | Mechanism yet to be determined | [186] | ||
| BP-2109 | [187] | |||
| BP13944 | [188] | |||
| BT 24 (quinoline compound) | [189] | |||
| Aminobenzamide | [190] | |||
| 2,5,6-trisubstituted pyrazine compounds | [191] | |||
| Furin | [182] | |||
| Protegrin-1 | [192] | |||
| Retrocyclin-1 | [193] | |||
| Chalcone derivatives (DENV-2) | [194] | |||
| Flavonoids (fingerroot) (DENV-2) |
[194] | |||
| Tyrothricin | Competitive inhibition | [195] | ||
| Derivatives of Guanidinylated 2,5-dideoxystreptamine | [181] | |||
| Retrotripeptides: R-Arg-Lys-Nle-NH2 Ivermectin Selamectin Benezethonium chloride |
Mixed inhibition | [196] [195] |
||
| Peptide-boronic acid | C-terminal electrophile incorporation | [173] | ||
| 3 | ZIKV (Zika Virus) |
Peptidomimetic boronic acid | Formation of salt bridge with Asp83 of NS2B | [95] |
| Bromocriptine | Mechanism yet to be determined | [197] | ||
| Novobiocin | [198] | |||
| Hydroxychloroquine | [199] | |||
| Erythrosin B | [200] | |||
| Theaflavin-3,3′-digallate | [201] | |||
| 9b (HIV protease inhibitor) | [202] | |||
| 2,5,6-trisubstituted pyrazine compounds | [191] | |||
| Aprotinin | [75] | |||
| 4 | JEV (Japanese Encephalitis Virus) |
NSC135618 | Inhibits the conformational change of NS2B (allosteric inhibitor) | [203] |
| 5 | YFV (Yellow fever Virus) |
Erythrosin B | Mechanism yet to be determined | [200] |