Could a plant metabolite in liverworts be a potent antiviral against SARS-CoV-2 and other RNA viruses?

mRNA technology has been essential in protecting against the original severe acute respiratory coronavirus 2 (SARS-CoV-2). Still, there have been some vocal opponents against the vaccine, raising concerns over the safety and effectiveness of the vaccines. While getting vaccinated remains the best way to protect yourself and others, some scientists are getting back to nature for help in developing natural antiviral medicine.

A new study from the National Centre for Biotechnology and Medicinal Chemistry Institute suggests Mother Nature delivered — in the form of liverworts. They found that the bryophyte Marchantia polymorpha, also known as umbrella liverworts, could work as a potential antiviral treatment.

A plant metabolite in liverwort that’s found in chlorophyll is called pheophorbide a (pheoA). Results show it can prevent viral entry into cells. Its antiviral effects were also effective against other positive-strand RNA viruses such as West Nile, HCV, and other coronaviruses.

PheoA also has an additive effect and small synergy with remdesivir. Therefore, the combined treatment could improve remdesivir’s effectiveness.

The researchers write:

“Our results indicate that PheoA displays a remarkable potency and a satisfactory therapeutic index, and suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.”

The research study “SARS-CoV-2 fears green: the chlorophyll catabolite Pheophorbide a is a potent antiviral” is available on the preprint bioRxiv* server.

Study details

The research team evaluated the antiviral potential of several liverwort plants against SARS-CoV-2. They used a bioactivity-guided chromatographic method along with mass-spectrometry to identify the plant metabolite Pheo A as a potential candidate.

Antiviral activity and PheoA’s mechanism of action

The study results show that PheoA could inactivate RNA viruses such as SARS-CoV-2 by preventing early viral infection in cells.

The virtual lack of activity of PheoA at post-entry levels may be explained by the fact that PheoA can only act on the viral particle, or that PheoA requires longer incubation periods to penetrate the cell and interfere with downstream steps of the virus lifecycle,” explained the researchers.

PheoA’s mechanism of action is through targeting viral particles to inactivate them and prevent SARS-CoV-2 infection.

The researchers also explored how it renders the virus noninfectious. Previous studies have suggested PheoA could alter the properties of the viral envelope lipid bilayer.

The results showed PheoA is selective in its inactivation as it only stopped infection in positive-strand RNA viruses. In contrast, PheoA’s antiviral effects were nonexistent with positive-strand RNA viruses such as VSV. This indicates that PheoA likely acts by modulating the viral membrane’s lipidic composition.

Advantages of PheoA

PheoA appeared similar in composition to animal Protoporphyrin IX, which has been known for strong antiviral effects. But a benefit of PheoA over Protoporphyrin IX is that it is nontoxic.

PheoA is also more accessible as it can be acquired from plant and algae chlorophyll. Having chlorophyllase activity exposed to the heat produced more PheoA.

The researchers also note that PheoA could boost the effectiveness of remdesivir. PheoA was added in increasing doses to remdesivir in cell cultures. The findings showed an additive effect with no cross inhibition in antiviral activity. In addition, PheoA showed slight synergistic activity with remdesivir.

These results suggest that combinations of PheoA with other antivirals may result beneficial, as it was observed by its additive effect in combination with remdesivir in cell culture infection models.”

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Jocelyn Solis-Moreira

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.

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