Background: The deadly outbreak of COVID-19 disease caused by novel SARS CoV2
has created an unprecedented global health crisis affecting every sectors of human life and enormous
damage to world’s economy. With >16.1 million infections and >650,000 deaths worldwide
as of July 27, 2020, there is no treatment for this disease neither is there any available vaccine. Serious
research efforts are ongoing on all fronts including treatment, prevention and diagnosis to combat
the spread of this infection. A number of targets that include both viral and host proteins have
been identified and became part of intense investigation. In this respect the viral surface spike (S)
glycoprotein caught the attention most. It is cleaved by multiple host proteases to allow recognition
by host receptor human Angiotensin Converting Enzyme2 (hACE2) leading to fusion and viral replication.
Natural products, small compounds, antioxidants, peptides, proteins, oligonucleotides,
antibodies and other compounds are under investigation for development of antiviral agents against
Objective: Recently cholesterol lowering phytocompounds Quercetin, Swertiamarin and Berberine
which promote human Low Density Lipoprotein Receptor (hLDLR) via inhibition of human Proprotein
Convertase Subtilisin Kexin9 (hPCSK9) have been shown to block viral infections caused
by ebola, influenza, Respiratory Syncytial Virus (RSV), Hepatitis C virus (HCV) and other RNA
type viruses. Since SARS CoV2 is a RNA virus with similar genetic structure and infection machinery,
it is hypothesised that these phytocompounds may also exhibit antiviral property against
Methods: Our above concept is based on recently published studies as well as our herein presented
in silico modeling and computational data which suggested strong interactions of hPCSK9 with
above phytocompounds and most importantly with hACE2 following its complexation with receptor
binding domain (RBD) of SARS CoV2 S protein.
Results: These results and a proposed schematic model showing association of hPCSK9 with
SARS CoV2 infection are presented in this manuscript. It is proposed that hPCSK9 plays the role
of a co-receptor in binding with hACE2:RBD complex and thereby facilitates viral fusion.
Conclusion: Our studies suggest that PCSK9 inhibitors may provide beneficial effect against
COVID-19 infection by retarding viral fusion through displacement of bound hPCSK9 from its
complex with ACE2:RBD of SARS CoV2 S protein.