Antiviral activity of lycorine against Zika virus in vivo and in vitro

Abstract

The emergence and re-emergence of Zika virus (ZIKV), is a cause for international concern. These highly pathogenic arboviruses represent a serious health burden in tropical and subtropical areas worldwide. Despite these burdens, antiviral therapies do not exist, and inhibitors of ZIKV are therefore urgently needed. To elucidate the anti-ZIKV effect of lycorine, we used reverse transcription-quantitative real-time PCR (qRT-PCR), immunofluorescence, Westernwestern blot, and plaque forming assay to analyse viral RNA (vRNA), viral protein, progeny virus counts, and validated inhibitors in vitro using a variety of cell lines. Additionally, we found that lycorine acts post-infection according to time-of-addition assay, and inhibits RdRp activity. Lycorine protected AG6 mice against ZIKV-induced lethality by decreasing the viral load in the blood. Due to its potency and ability to target ZIKV infection in vivo and in vitro, lycorine might offer promising therapeutic possibilities for combatting ZIKV infections in the future.

Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections

“…Meanwhile, the expression level of FLuc is used as the internal control to normalize NLuc activity. Since it was previously reported that lycorine inhibited the ZIKA virus by blocking RdRp activity in the in vitro RNA polymerase assay ( Chen et al, 2020 ), we examined the effect of lycorine on MERS-CoV RdRp activity using the cell-based MERS-CoV RdRp activity reporter assay. First, we evaluated lycorine cytotoxicity in HEK293 cells.…”

“…Lycorine was reported to suppress viral RNA replication and viral protein synthesis of poliovirus ( Hwang et al, 2008 ), EV71 virus ( Liu et al, 2011 ) and avian influenza virus H5N1 ( Liu et al, 2011 ). Recently, it was suggested that lycorine could inhibit Zika virus viral RNA synthesis and bind to the Zika RdRp protein ( Chen et al, 2020 ). RdRp of RNA viruses is known to be one of the most important viral proteins for viral RNA synthesis.…”

Amino acid–derived defense metabolites from plants: A potential source to facilitate novel antimicrobial development

“…Lycorine also inhibits flaviviruses such as West Nile virus (WNV), dengue virus (DENV), and yellow fever virus; however, a single amino acid substitution in the WNV 2K peptide was sufficient to confer lycorine resistance ( 237 ). In mice models, lycorine also possesses antiviral activity against the Zika virus (ZIKV) and inhibits RNA-dependent RNA polymerase ( 214 ) and, as a consequence, decreases the viral load. This is an important development since currently no vaccine or specific antiviral treatment is approved for ZIKV.…”

A review study on the anti-trichomonas activities of medicinal plants

“…This natural alkaloid has immense therapeutic potential as it has shown high specificity in a very low concentration against several cancers both in vivo and in vitro and against various drug-resistant cancer cells ( Roy et al, 2018 ). Recently, lycorine showed anti-viral activity against the Zika virus in vitro and in vivo ( Chen et al, 2020 ). Giordani et al (2011) studied the cytotoxicity of lycorine against T. vaginalis covering a very broad range of concentrations from 2.5 to 1000 μM.…”