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Synthesis and Antiviral Activity of Novel β-D-N4-Hydroxycytidine Ester Prodrugs as Potential Compounds for the Treatment of SARS-CoV-2 and Other Human Coronaviruses.

Synthesis and Antiviral Activity of Novel β-D-N4-Hydroxycytidine Ester Prodrugs as Potential Compounds for the Treatment of SARS-CoV-2 and Other Human Coronaviruses.

Authors :
Darnotuk ES
Siniavin AE
Shastina NS
Luyksaar SI
Inshakova AM
Bondareva NE
Zolotov SA
Lubenec NL
Sheremet AB
Logunov DY
Zigangirova NA
Gushchin VA
Gintsburg AL
Source :
Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Dec 26; Vol. 17 (1). Date of Electronic Publication: 2023 Dec 26.
Publication Year :
2023

Abstract

The spread of COVID-19 infection continues due to the emergence of multiple transmissible and immune-evasive variants of the SARS-CoV-2 virus. Although various vaccines have been developed and several drugs have been approved for the treatment of COVID-19, the development of new drugs to combat COVID-19 is still necessary. In this work, new 5'-O-ester derivatives of N4-hydroxycytidine based on carboxylic acids were developed and synthesized by Steglich esterification. The antiviral activity of the compounds was assessed in vitro-inhibiting the cytopathic effect of HCoV-229E, and three variants of SARS-CoV-2, on huh-7 and Vero E6 cells. Data have shown that most synthesized derivatives exhibit high activity against coronaviruses. In addition, the relationship between the chemical structure of the compounds and their antiviral effect has been established. The obtained results show that the most active compound was conjugate SN_22 based on 3-methyl phenoxyacetic acid. The results of this study indicate the potential advantage of the chemical strategies used to modify NHC as a promising avenue to be explored in vivo, which could lead to the development of drugs with improved pharmacological properties that potently inhibit SARS-CoV-2.

Details

Language :
English
ISSN :
1424-8247
Volume :
17
Issue :
1
Database :
MEDLINE
Journal :
Pharmaceuticals (Basel, Switzerland)
Publication Type :
Academic Journal
Accession number :
38256869
Full Text :
https://doi.org/10.3390/ph17010035