Liquiritin inhibits replication of novel coronaviruses, the latest research from a team of researchers at Peking University found.
Xie Zhengwei's team at Peking University and Qin Zhengfeng's team at the Academy of Military Medical Sciences collaborated to publish a research paper entitled "An artificial intelligence system reveals liquiritin inhibits SARSCoV-2 by mimicking type I interferon" on the bioRxiv website.
The study found that one of the main components of licorice, liquiritin, inhibited the replication of SARS-CoV-2 in Vero cells with an EC50 of 2.39M through its in-house developed artificial intelligence drug efficacy prediction system.
This study analyzed the cellular transcriptome changes after liquiritin action, revealed the potential antiviral mechanism of liquiritin, and evaluated the safety of liquiritin at the mouse level, laying the foundation for its druggability.
The outbreak of pneumonia (COVID-19) caused by the novel coronavirus (SARS-CoV-2) infection has been classified by the World Health Organization as a public health emergency of international concern, with more than 3.3 million confirmed cases and 230,000 deaths worldwide as of May 2.
There are still no effective drugs for the new coronavirus.
Most current antiviral drug development is focused on blocking viral receptors or inhibiting viral proteases, and enhancing host antivirals is rarely considered.
Viruses are parasitic organisms that must rely on host replication, and host-targeted drugs not only effectively inhibit the rapid replication of viral nucleic acids, but also fight viral resistance mutations, so host-targeted anti-new coronavirus drugs are the team's goal.
The team first screened anti-SARS-CoV-2 drug candidate liquiritin through its self-developed artificial intelligence drug efficacy prediction platform, and its in vitro antiviral experiments showed that liquiritin significantly inhibited SARS-CoV-2 replication in Vero cells, with an in vitro antiviral effect similar to chloroquine.
The study further analyzed the transcriptome of MCF7 cells after liquiritin action.
GO functional enrichment analysis found that the type I interferon signaling pathway, negative regulation of viral genome replication, defense response to virus and response to virus were up-regulated and inflammatory response-related functional genes were down-regulated after the action of liquiritin.
Further protein-protein interaction network analysis of the up-regulated genes revealed that the most important module contained nine interferon-related genes, which suggested that liquiritin may exert anti-SARS-CoV-2 effects by mimicking type I interferon.
To advance the clinical translation of liquiritin, the team further evaluated the safety of intravenous and intraperitoneal administration of liquiritin at the mouse level.
Experiments showed that liquiritin was administered intravenously at 150mg/kg single dose and intraperitoneally at 300mg/kg for 7 consecutive days with no obvious toxic side effects, mice had normal body weight and drinking water, white blood cells, red blood cells and platelets were in the normal range, and the results of blood biochemical analysis showed that its liver function, kidney function and heart function were normal, which laid the foundation for the evaluation of the druggability of liquiritin.
Liquiritin is one of the major flavonoids in licorice and one of the main components of compounded licorice tablets, and has a variety of physiological activities such as antioxidant, antidepressant, neuroprotective and anti-inflammatory.
It has been reported that patients with severe cases of novel coronavirus pneumonia suffer more from cytokine storm syndrome (CSS), and liquiritin has multiple antiviral and anti-inflammatory activities, and has multiple advantages in the treatment of novel coronavirus pneumonia, and is expected to be developed as a new drug against SARS-CoV-2, which also prepares the stockpile of drug candidates for future coronavirus infectious disease prevention and control war.
Special Report: Fighting The New Coronavirus
