The Local Anaesthetic Procaine Prodrugs ProcCluster<sup>®</sup> and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In Vitro

As vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer disease courses, and lately, considerable efforts have been undertaken to repurpose existing drugs as antivirals. The local anaesthe...

Full description

Bibliographic Details
Main Authors: Clio Häring, Johannes Jungwirth, Josefine Schroeder, Bettina Löffler, Beatrice Engert, Christina Ehrhardt
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/19/14584
_version_ 1797575844010393600
author Clio Häring
Johannes Jungwirth
Josefine Schroeder
Bettina Löffler
Beatrice Engert
Christina Ehrhardt
author_facet Clio Häring
Johannes Jungwirth
Josefine Schroeder
Bettina Löffler
Beatrice Engert
Christina Ehrhardt
author_sort Clio Häring
collection DOAJ
description As vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer disease courses, and lately, considerable efforts have been undertaken to repurpose existing drugs as antivirals. The local anaesthetic procaine has been investigated for antiviral properties against several viruses over the past decades. Here, we present data on the inhibitory effect of the procaine prodrugs ProcCluster<sup>®</sup> and procaine hydrochloride on SARS-CoV-2 infection in vitro. Both procaine prodrugs limit SARS-CoV-2 progeny virus titres as well as reduce interferon and cytokine responses in a proportional manner to the virus load. The addition of procaine during the early stages of the SARS-CoV-2 replication cycle in a cell culture first limits the production of subgenomic RNA transcripts, and later affects the replication of the viral genomic RNA. Interestingly, procaine additionally exerts a prominent effect on SARS-CoV-2 progeny virus release when added late during the replication cycle, when viral RNA production and protein production are already largely completed.
first_indexed 2024-03-10T21:44:01Z
format Article
id doaj.art-c107471c19884adcba28c26b5c839604
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-10T21:44:01Z
publishDate 2023-09-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-c107471c19884adcba28c26b5c8396042023-11-19T14:28:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191458410.3390/ijms241914584The Local Anaesthetic Procaine Prodrugs ProcCluster<sup>®</sup> and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In VitroClio Häring0Johannes Jungwirth1Josefine Schroeder2Bettina Löffler3Beatrice Engert4Christina Ehrhardt5Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, 07745 Jena, GermanySection of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, 07745 Jena, GermanySection of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, 07745 Jena, GermanyInstitute of Medical Microbiology, Jena University Hospital, 07747 Jena, GermanyInflamed Pharma GmbH, 07745 Jena, GermanySection of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, 07745 Jena, GermanyAs vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer disease courses, and lately, considerable efforts have been undertaken to repurpose existing drugs as antivirals. The local anaesthetic procaine has been investigated for antiviral properties against several viruses over the past decades. Here, we present data on the inhibitory effect of the procaine prodrugs ProcCluster<sup>®</sup> and procaine hydrochloride on SARS-CoV-2 infection in vitro. Both procaine prodrugs limit SARS-CoV-2 progeny virus titres as well as reduce interferon and cytokine responses in a proportional manner to the virus load. The addition of procaine during the early stages of the SARS-CoV-2 replication cycle in a cell culture first limits the production of subgenomic RNA transcripts, and later affects the replication of the viral genomic RNA. Interestingly, procaine additionally exerts a prominent effect on SARS-CoV-2 progeny virus release when added late during the replication cycle, when viral RNA production and protein production are already largely completed.https://www.mdpi.com/1422-0067/24/19/14584SARS-CoV-2local anaestheticsprocaineantivirals
spellingShingle Clio Häring
Johannes Jungwirth
Josefine Schroeder
Bettina Löffler
Beatrice Engert
Christina Ehrhardt
The Local Anaesthetic Procaine Prodrugs ProcCluster<sup>®</sup> and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In Vitro
International Journal of Molecular Sciences
SARS-CoV-2
local anaesthetics
procaine
antivirals
title The Local Anaesthetic Procaine Prodrugs ProcCluster<sup>®</sup> and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In Vitro
title_full The Local Anaesthetic Procaine Prodrugs ProcCluster<sup>®</sup> and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In Vitro
title_fullStr The Local Anaesthetic Procaine Prodrugs ProcCluster<sup>®</sup> and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In Vitro
title_full_unstemmed The Local Anaesthetic Procaine Prodrugs ProcCluster<sup>®</sup> and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In Vitro
title_short The Local Anaesthetic Procaine Prodrugs ProcCluster<sup>®</sup> and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In Vitro
title_sort local anaesthetic procaine prodrugs proccluster sup r sup and procaine hydrochloride impair sars cov 2 replication and egress in vitro
topic SARS-CoV-2
local anaesthetics
procaine
antivirals
url https://www.mdpi.com/1422-0067/24/19/14584
work_keys_str_mv AT clioharing thelocalanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT johannesjungwirth thelocalanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT josefineschroeder thelocalanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT bettinaloffler thelocalanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT beatriceengert thelocalanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT christinaehrhardt thelocalanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT clioharing localanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT johannesjungwirth localanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT josefineschroeder localanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT bettinaloffler localanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT beatriceengert localanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro
AT christinaehrhardt localanaestheticprocaineprodrugsprocclustersupsupandprocainehydrochlorideimpairsarscov2replicationandegressinvitro