Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2

Francisco Faísca; Vanessa  Correia; Željko Petrovski; Luís C. Branco; Helena Rebelo-de-Andrade; Miguel M. Santos

doi:10.3390/pharmaceutics14040877

Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2

Francisco Faísca, Vanessa Correia, Željko Petrovski, Luís C. Branco, Helena Rebelo-de-Andrade, Miguel M. Santos

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Abstract

The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH₂ ][C₁ SO₃ ]₂ and [HCQH₂ ][GlcCOO]₂, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH₂ ][SO₄ ]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH₂ ][GlcCOO]₂ . Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra-and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.

Original language	English
Article number	877
Number of pages	21
Journal	Pharmaceutics
Volume	14
Issue number	4
DOIs	https://doi.org/10.3390/pharmaceutics14040877
Publication status	Published - 17 Apr 2022

Keywords

API-ILs
COVID-19
hydroxychloroquine
pharmaceutical ionic liquids
SARS-CoV-2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/pharmaceutics14040877Licence: CC BY

Enhanced In Vitro Antiviral Activity of HydroxychloroquineFinal published version, 4.44 MBLicence: CC BY

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@article{3e92629a79a94a35a46a84b0656a0d84,

title = "Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2",

abstract = "The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2 ][C1 SO3 ]2 and [HCQH2 ][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2 ][SO4 ]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2 ][GlcCOO]2 . Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra-and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.",

keywords = "API-ILs, COVID-19, hydroxychloroquine, pharmaceutical ionic liquids, SARS-CoV-2",

author = "Francisco Fa{\'i}sca and Vanessa Correia and {\v Z}eljko Petrovski and Branco, {Lu{\'i}s C.} and Helena Rebelo-de-Andrade and Santos, {Miguel M.}",

note = "Funding: info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT# info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT# info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-QOR%2F32406%2F2017/PT# The authors also thank Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia for the projects Research 4 COVID-19 no. 582, and RECI/BBBBQB/0230/2012. The authors also acknowledge the Solchemar company. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/pharmaceutics14040877",

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T1 - Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2

AU - Faísca, Francisco

AU - Correia, Vanessa

AU - Petrovski, Željko

AU - Branco, Luís C.

AU - Rebelo-de-Andrade, Helena

AU - Santos, Miguel M.

N1 - Funding: info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT# info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT# info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-QOR%2F32406%2F2017/PT# The authors also thank Fundação para a Ciência e Tecnologia for the projects Research 4 COVID-19 no. 582, and RECI/BBBBQB/0230/2012. The authors also acknowledge the Solchemar company. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/4/17

Y1 - 2022/4/17

N2 - The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2 ][C1 SO3 ]2 and [HCQH2 ][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2 ][SO4 ]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2 ][GlcCOO]2 . Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra-and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.

AB - The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2 ][C1 SO3 ]2 and [HCQH2 ][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2 ][SO4 ]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2 ][GlcCOO]2 . Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra-and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.

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DO - 10.3390/pharmaceutics14040877

M3 - Article

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AN - SCOPUS:85129288351

SN - 1999-4923

VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

IS - 4

M1 - 877

ER -

Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2

Abstract

Keywords

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