PDF(Pubmed)
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.
摘要：
随着SARS-CoV-2疫苗接种工作在许多国家取得进展，对于那些患有严重疾病的人，仍然迫切需要有效的抗病毒治疗策略，最近,已经做出了相当大的努力来重新利用现有药物作为抗病毒药物。在过去的几十年中，已经研究了局部麻醉剂普鲁卡因对几种病毒的抗病毒特性。这里,我们提供了普鲁卡因前药ProcCluster®和盐酸普鲁卡因对SARS-CoV-2感染的体外抑制作用的数据。两种普鲁卡因前药均限制SARS-CoV-2子代病毒滴度，并以与病毒载量成比例的方式降低干扰素和细胞因子反应。在细胞培养中SARS-CoV-2复制周期的早期阶段添加普鲁卡因首先限制了亚基因组RNA转录本的产生，然后影响病毒基因组RNA的复制。有趣的是,普鲁卡因在复制周期后期添加时，还对SARS-CoV-2子代病毒释放产生显著影响，当病毒RNA生产和蛋白质生产已经基本完成时。
