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bioRxiv · 10.1101/2020.08.19.257022

Targeting pentose phosphate pathway for SARS-CoV-2 therapy

Bojkova, D.·Costa, R.·Bechtel, M.·Ciesek, S.·Michaelis, M.·Cinatl, J.
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Abstract

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.

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Bojkova, D., Costa, R., Bechtel, M., Ciesek, S., Michaelis, M., Cinatl, J.. 2020-08-21. Targeting pentose phosphate pathway for SARS-CoV-2 therapy. https://doi.org/10.1101/2020.08.19.257022

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