Theoretical insights into the effect of halogenated substituent on the electronic structure and spectroscopic properties of the favipiravir tautomeric forms and its implications for the treatment of COVID-19

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18450%2F21%3A50018550" target="_blank" >RIV/62690094:18450/21:50018550 - isvavai.cz</a>

Alternative codes found

RIV/62690094:18470/21:50018550

Result on the web

<a href="https://pubs.rsc.org/en/content/articlelanding/2021/RA/D1RA06309J" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2021/RA/D1RA06309J</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d1ra06309j" target="_blank" >10.1039/d1ra06309j</a>

Result language

angličtina

Original language name

Theoretical insights into the effect of halogenated substituent on the electronic structure and spectroscopic properties of the favipiravir tautomeric forms and its implications for the treatment of COVID-19

Original language description

In this study, we systematically investigated the electronic structure, spectroscopic (nuclear magnetic resonance, infrared, Raman, electron ionization mass spectrometry, UV-Vis, circular dichroism, and emission) properties, and tautomerism of halogenated favipiravir compounds (fluorine, chlorine, and bromine) from a computational perspective. Additionally, the effects of hydration on the proton transfer mechanism of the tautomeric forms of the halogenated favipiravir compounds are discussed. Our results suggest that spectroscopic properties allow for the elucidation of such tautomeric forms. As is well-known, the favipiravir compound has excellent antiviral properties and hence was recently tested for the treatment of new coronavirus (SARS-CoV-2). Through in silico modeling, in the current study, we evaluate the role of such tautomeric forms in order to consider the effect of drug-metabolism in the inhibition process of the main protease (M-pro) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 virus. According to the molecular docking, all halogenated compounds presented a better interaction energy than the co-crystallized active ligand (-3.5 kcal mol(-1)) in the viral RdRp, in both wild-type (-6.3 to -6.5 kcal mol(-1)) and variant (-5.4 to -5.6 kcal mol(-1)) models. The variant analyzed for RdRp (Y176C) decreases the affinity of the keto form of the compounds in the active site, and prevented the ligands from interacting with RNA. These findings clearly indicated that all these compounds are promising as drug candidates for this molecular target.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10406 - Analytical chemistry

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

RSC ADVANCES

ISSN

2046-2069

e-ISSN

—

Volume of the periodical

11

Issue of the periodical within the volume

56

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

35228-35244

UT code for WoS article

000713408900001

EID of the result in the Scopus database

2-s2.0-85119854240