Novel COVID-19 therapy based on natural products with anti-SARS-CoV-2 activity

ABSTRACT

The outbreak of the COVID-19 pandemic in late 2019 has so far caused more than 6 million deaths worldwide according to WHO. Currently, there is only one FDA-approved novel antiviral drug therapy (Paxlovid, Pfizer) for treatment of critically ill patients from COVID-19 infection. However, there is a need for a great diversity of antiviral therapies because of the constant mutations of the virus and the possibility of other similar viruses causing similar symptoms in patients. By utilizing natural products from medicinal plants, it is possible to provide a drug, or drug leads for a future novel antiviral therapy. Currently, we are testing isolated and characterized natural products (some novel and some already elucidated) from water lily (Nuphar lutea) and eagle fern (Pteridium aquilinum) on the SARS-CoV-2 virus where we are working on developing a good pipeline to test these compounds in vitro. So far, we have tested the effect of the compounds on inhibition of cell entry using a pseudovirus system and HEK293-FT cells transiently transfected with SARS-CoV-2 receptors ACE-2 and TMPRSS2. Some of the compounds showed a slightly inhibitory effect. Next steps will be to establish a cell line with stable expression of ACE-2 and TMPRSS2 and confirm the results in cells with endogenous expression of these receptors. We will proceed working with different variants of the hospital isolates of the virus within the next months, where we will further analyse the potential effect of these compounds on viral replication. The goal is to determine and understand the mechanism of inhibitory action of the natural products on the virus. In conclusion, we are at an early stage of researching the abundant possibilities of antiviral effects of these natural products on SARS-CoV-2.