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Basic Characteristics of Mutations
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Mutation Site
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L452R |
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Mutation Site Sentence
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Table 1 |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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Delta |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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-
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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38685970
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Title
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5-chloro-3-(2-(2,4-dinitrophenyl) hydrazono)indolin-2-one: synthesis, characterization, biochemical and computational screening against SARS-CoV-2
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Author
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Majoumo-Mbe F,Sangbong NA,Tadjong Tcho A,Namba-Nzanguim CT,Simoben CV,Eni DB,Alhaji Isa M,Poli ANR,Cassel J,Salvino JM,Montaner LJ,Tietjen I,Ntie-Kang F
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Journal
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Chemicke zvesti
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Journal Info
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2024;78(6):3431-3441
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Abstract
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Chemical prototypes with broad-spectrum antiviral activity are important toward developing new therapies that can act on both existing and emerging viruses. Binding of the SARS-CoV-2 spike protein to the host angiotensin-converting enzyme 2 (ACE2) receptor is required for cellular entry of SARS-CoV-2. Toward identifying new chemical leads that can disrupt this interaction, including in the presence of SARS-CoV-2 adaptive mutations found in variants like omicron that can circumvent vaccine, immune, and therapeutic antibody responses, we synthesized 5-chloro-3-(2-(2,4-dinitrophenyl)hydrazono)indolin-2-one (H(2)L) from the condensation reaction of 5-chloroisatin and 2,4-dinitrophenylhydrazine in good yield. H(2)L was characterised by elemental and spectral (IR, electronic, Mass) analyses. The NMR spectrum of H(2)L indicated a keto-enol tautomerism, with the keto form being more abundant in solution. H(2)L was found to selectively interfere with binding of the SARS-CoV-2 spike receptor-binding domain (RBD) to the host angiotensin-converting enzyme 2 receptor with a 50% inhibitory concentration (IC(50)) of 0.26 muM, compared to an unrelated PD-1/PD-L1 ligand-receptor-binding pair with an IC(50) of 2.06 muM in vitro (Selectivity index = 7.9). Molecular docking studies revealed that the synthesized ligand preferentially binds within the ACE2 receptor-binding site in a region distinct from where spike mutations in SARS-CoV-2 variants occur. Consistent with these models, H(2)L was able to disrupt ACE2 interactions with the RBDs from beta, delta, lambda, and omicron variants with similar activities. These studies indicate that H(2)L-derived compounds are potential inhibitors of multiple SARS-CoV-2 variants, including those capable of circumventing vaccine and immune responses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11696-023-03274-5.
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Sequence Data
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-
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