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A Host-Harbored Metabolic Susceptibility of Coronavirus Enables Broad-Spectrum Targeting

Fang, H.; Wang, Y.; Liu, L.; Cheng, K.; Li, P.; Tan, Y.; Hao, X.; Mei, M.; Xu, X.; Yao, Y.; Zan, F.; Wu, L.; Zhu, Y.; Xu, B.; Huang, D.; Wang, C.; Tan, X.; Qian, Z.; Chen, X.-W.

2022-12-10 cell biology
10.1101/2022.12.07.519404 bioRxiv
Show abstract

Host-based antivirals could offer broad-spectrum therapeutics and prophylactics against the constantly-mutating viruses including the currently-ravaging coronavirus, yet must target cellular vulnerabilities of viruses without grossly endangering the host. Here we show that the master lipid regulator SREBP1 couples the phospholipid scramblase TMEM41B to constitute a host "metabolism-to-manufacture" cascade that maximizes membrane supplies to support coronaviral genome replication, harboring biosynthetic enzymes including Lipin1 as druggable viral-specific-essential (VSE) host genes. Moreover, pharmacological inhibition of Lipin1, by a moonlight function of the widely-prescribed beta-blocker Propranolol, metabolically uncouples the SREBP1-TMEM41B cascade and consequently exhibits broad-spectrum antiviral effects against coronaviruses, Zika virus, and Dengue virus. The data implicate a metabolism-based antiviral strategy that is well tolerated by the host, and a potential broad-spectrum medication against current and future coronavirus diseases.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

1
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Top 0.3%
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22
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25
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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.