Is lithium a potential treatment for the novel Wuhan (2019-nCoV) coronavirus? A scoping review

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Abstract

The current rapid spread of the novel coronavirus (2019-nCoV) originating from Wuhan, China, calls for a rapid response from the research community. Lithium is widely used to treat bipolar disorder, but has been shown to exhibit antiviral activity. This brief review took a systematic approach to identify five in vitro studies reporting on the influence of lithium on coronaviral infections. We propose that in the case of urgent need, lithium be explored as a potential treatment or prophylaxis for the novel Wuhan coronavirus (2019-nCoV).

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Nucleocapsid Phosphorylation and RNA Helicase DDX1 Recruitment Enables Coronavirus Transition from Discontinuous to Continuous Transcription

Chia-Hsin Wu, Pei-Jer Chen, Shiou-Hwei Yeh (2014)

Summary Coronaviruses contain a positive-sense single-stranded genomic (g) RNA, which encodes nonstructural proteins. Several subgenomic mRNAs (sgmRNAs) encoding structural proteins are generated by template switching from the body transcription regulatory sequence (TRS) to the leader TRS. The process preferentially generates shorter sgmRNA. Appropriate readthrough of body TRSs is required to produce longer sgmRNAs and full-length gRNA. We find that phosphorylation of the viral nucleocapsid (N) by host glycogen synthase kinase-3 (GSK-3) is required for template switching. GSK-3 inhibition selectively reduces the generation of gRNA and longer sgmRNAs, but not shorter sgmRNAs. N phosphorylation allows recruitment of the RNA helicase DDX1 to the phosphorylated-N-containing complex, which facilitates template readthrough and enables longer sgmRNA synthesis. DDX1 knockdown or loss of helicase activity markedly reduces the levels of longer sgmRNAs. Thus, coronaviruses employ a unique strategy for the transition from discontinuous to continuous transcription to ensure balanced sgmRNAs and full-length gRNA synthesis.

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Lithium chloride inhibits the coronavirus infectious bronchitis virus in cell culture

Sally Harrison, Ian Tarpey, Lisa Rothwell … (2007)

The avian coronavirus infectious bronchitis virus (IBV) is a major economic pathogen of domestic poultry that, despite vaccination, causes mortality and significant losses in production. During replication of the RNA genome there is a high frequency of mutation and recombination, which has given rise to many strains of IBV and results in the potential for new and emerging strains. Currently the live-attenuated vaccine gives poor cross-strain immunity. Effective antiviral agents may therefore be advantageous in the treatment of IBV. Lithium chloride (LiCl) is a potent inhibitor of the DNA virus herpes simplex virus but not RNA viruses. The effect of LiCl on the replication of IBV was examined in cell culture using two model cell types; Vero cells, an African Green monkey kidney-derived epithelial cell line; and DF-1 cells, an immortalized chicken embryo fibroblast cell line. When treated with a range of LiCl concentrations, IBV RNA and protein levels and viral progeny production were reduced in a dose-dependent manner in both cell types, and the data indicated that inhibition was a cellular rather than a virucidal effect. Host cell protein synthesis still took place in LiCl-treated cells and the level of a standard cellular housekeeping protein remained unchanged, indicating that the effect of LiCl was specifically against IBV.

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Comparative analysis of the effect of glycyrrhizin diammonium and lithium chloride on infectious bronchitis virus infection in vitro.

Guangxing Li, Jiechao Yin, Qi-Jing Li … (2009)

The effects of glycyrrhizin diammonium (GD) and lithium chloride (LiCl) on cell infection by avian infectious bronchitis virus (IBV) were investigated using cytopathic effect observation, plaque-reduction assay and reverse transcriptase-polymerase chain reaction. The anti-viral effect of GD and LiCl on virus, on virus-infected cells or on cells pre-treated by both drugs was analysed, respectively. Our results showed that GD had a direct antiviral activity, leading to complete inhibition of cell infection. The cell infection was not alleviated by either pre-treatment of cells with GD or addition of the drug post infection, confirming that the inhibitory effect of GD, unlike LiCl, on IBV is a viral factor, rather than a cellular factor. The inhibitory effect of both drugs was confirmed by infecting primary chicken embryo kidney cells. In addition, apoptosis of infected cells was positively related with cytopathic effect and could be inhibited by effective drug treatment. Our data indicate that GD and LiCl have potential to prevent IBV infection in vitro through different antiviral mechanisms. The data are helpful for using antivirals efficiently.