Synthesis and biological evaluation of new ß-D-N4-hydroxycytidine analogs against SARS-CoV-2, influenza viruses and DENV-2.
Bioorg Med Chem Lett
; 83: 129174, 2023 03 01.
Article
in English
| MEDLINE | ID: covidwho-2231477
ABSTRACT
Drug repurposing approach was applied to find a potent antiviral agent against RNA viruses such as SARS-CoV-2, influenza viruses and dengue virus with a concise strategy of small change in parent molecular structure. For this purpose, ß-D-N4-hydroxycytidine (NHC, 1) with a broad spectrum of antiviral activity was chosen as the parent molecule. Among the prepared NHC analogs (8a-g, and 9) from uridine, ß-D-N4-O-isobutyrylcytidine (8a) showed potent activity against SARS-CoV-2 (EC50 3.50 µM), Flu A (H1N1) (EC50 5.80 µM), Flu A (H3N2) (EC50 7.30 µM), Flu B (EC50 3.40 µM) and DENV-2 (EC50 3.95 µM) in vitro. Furthermore, its potency against SARS-CoV-2 was >5-fold, 3.4-fold, and 3-fold compared to that of NHC (1), MK-4482 (2), and remdesivir (RDV) in vitro, respectively. Ultimately, compound 8a was expected to be a potent inhibitor toward RNA viruses as a viral mutagenic agent like MK-4482.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Influenza A Virus, H1N1 Subtype
/
COVID-19
Type of study:
Experimental Studies
Limits:
Humans
Language:
English
Journal:
Bioorg Med Chem Lett
Journal subject:
Biochemistry
/
Chemistry
Year:
2023
Document Type:
Article
Affiliation country:
J.bmcl.2023.129174
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