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

Abstract

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® 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.

COVID-19 Pandemic: Therapeutic Strategies and Vaccines

“…One such drug under investigation is the local anesthetic procaine, which has been studied for its antiviral properties against various viruses in the past. Clio Häring et al in their study, present data on the inhibitory effects of two procaine prodrugs, ProcCluster ® and procaine hydrochloride, on SARS-CoV-2 infection in vitro [ 37 ]. Both of these procaine prodrugs demonstrate the ability to reduce SARS-CoV-2 progeny virus titers while also diminishing interferon and cytokine responses in a manner that is proportional to the viral load.…”