It becomes more and more obvious that deregulation of host metabolism play an important role in SARS-CoV-2 pathogenesis with implication for increased risk of severe course of COVID-19. Furthermore, it is expected that COVID-19 patients recovered from severe disease may experience long-term metabolic disorders. Thereby understanding the consequences of SARS-CoV-2 infection on host metabolism can facilitate efforts for effective treatment option. We have previously shown that SARS-CoV-2-infected cells undergo a shift towards glycolysis and that 2-deoxy-D-glucose (2DG) inhibits SARS-CoV-2 replication. Here, we show that also pentose phosphate pathway (PPP) is remarkably deregulated. Since PPP supplies ribonucleotides for SARS-CoV-2 replication, this could represent an attractive target for an intervention. On that account, we employed the transketolase inhibitor benfooxythiamine and showed dose-dependent inhibition of SARS-CoV-2 in non-toxic concentrations. Importantly, the antiviral efficacy of benfooxythiamine was further increased in combination with 2DG.

中文翻译：

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靶向磷酸戊糖途径用于SARS-CoV-2治疗

越来越明显的是，宿主代谢的失调在SARS-CoV-2发病机理中起着重要的作用，暗示着严重COVID-19病程的风险增加。此外，预计从严重疾病中康复的COVID-19患者可能会经历长期的代谢紊乱。从而了解SARS-CoV-2感染对宿主新陈代谢的影响，可以促进有效治疗方案的努力。先前我们已经表明，感染SARS-CoV-2的细胞发生了向糖酵解的转变，并且2-脱氧-D-葡萄糖（2DG）抑制了SARS-CoV-2的复制。在这里，我们显示了戊糖磷酸途径（PPP）也被显着解除管制。由于PPP为SARS-CoV-2复制提供了核糖核苷酸，因此这可能是一项有吸引力的干预目标。在这个帐户上，我们采用了转酮醇酶抑制剂苯氧乙硫胺并在无毒浓度下表现出剂量依赖性的SARS-CoV-2抑制作用。重要的是，与2DG组合使用时，苯氧乙硫胺的抗病毒功效进一步提高。