Pomegranate Peel Extract as an Inhibitor of SARS-CoV-2 Spike Binding to Human ACE2 Receptor (in vitro): A Promising Source of Novel Antiviral Drugs

Abstract

Plant extracts are rich in bioactive compounds, such as polyphenols, sesquiterpenes, and triterpenes, which potentially have antiviral activities. As a consequence of the coronavirus disease 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, thousands of scientists have been working tirelessly trying to understand the biology of this new virus and the disease pathophysiology, with the main goal of discovering effective preventive treatments and therapeutic agents. Plant-derived secondary metabolites may play key roles in preventing and counteracting the rapid spread of SARS-CoV-2 infections by inhibiting the activity of several viral proteins, in particular those involved in the virus entry into the host cells and its replication. Using in vitro approaches, we investigated the role of a pomegranate peel extract (PPE) in attenuating the interaction between the SARS-CoV-2 Spike glycoprotein and the human angiotensin-converting enzyme 2 receptor, and on the activity of the virus 3CL protease. Although further studies will be determinant to assess the efficacy of this extract in vivo, our results opened new promising opportunities to employ natural extracts for the development of effective and innovative therapies in the fight against SARS-CoV-2.

Physiological and Immune Functions of Punicalagin

“…The study reported that PUN was effective in suppressing human cytomegalovirus (HCMV) virus, herpes simplex virus (HSV-1), hepatitis C virus (HCV), respiratory syncytial virus (RSV), measles (MV) and dengue virus (DENV), at various concentrations without significant cytotoxicity [ 14 ]. Tito et al even reported in their study that PUN and EA inhibited the interaction between Spike protein and ACE2 and reduced viral 3CL protease activity in vitro, indicating the potential use of pomegranate extract as a prevention and treatment for SARS-CoV-2 disease [ 51 ].…”

More Is Always Better Than One: The N-Terminal Domain of the Spike Protein as Another Emerging Target for Hampering the SARS-CoV-2 Attachment to Host Cells

“…Different examples are available in the literature, mainly based on the application of Virtual Screening (VS) procedures [ 6 ]. Of note are research articles that have reported data properly validated by in-silico protocols (e.g., docking calibration) and/or in vitro assays for the identification of: (i) inhibitors of the SARS-CoV-2 main and papain-like proteases [ 3 , 4 , 7 ]; (ii) compounds targeting the receptor-binding domain (RBD) of the spike SARS-CoV-2 protein [ 5 , 8 ].…”

“…Notably, more recent studies indicate two other receptors involved in the SARS-CoV-2 attachment [ 8 ]: a transmembrane glycoprotein, CD147, localized on the surface of the host cell, and a chaperone heat shock protein, GRP78 [ 15 , 16 , 17 ]. Both could interact with several ligands as well as the RBD of the viral S protein, acting as multifunctional receptors for viral entry [ 8 ].…”

“…Notably, more recent studies indicate two other receptors involved in the SARS-CoV-2 attachment [ 8 ]: a transmembrane glycoprotein, CD147, localized on the surface of the host cell, and a chaperone heat shock protein, GRP78 [ 15 , 16 , 17 ]. Both could interact with several ligands as well as the RBD of the viral S protein, acting as multifunctional receptors for viral entry [ 8 ]. It is increasingly evident that many receptors are involved in the virus entry, and a recent study carried out by Singh M. et al [ 18 ], using a single-cell RNA expression map approach, identified unequivocally 28 SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs).…”

An Overview of COVID-19 and the Potential Plant Harboured Secondary Metabolites against SARS-CoV-2: A Review

“…P l a n t s e c o n d a r y m e t a b o l i t e s (PSM) in plants help combat biotic stresses (microorganisms, insects, parasites) and abiotic stresses (temperature, pH, water activity, heavy metals). In addition, these PSMs are also useful for humans, so plant and plant parts are used as nutraceuticals, drugs, and foodstuffs [9][10][11] . Plant secondary metabolites (PSMs) exhibiting antiviral activities by disturbing the viral particle constituents such as protein, lipid envelope, and genetic materials such as DNA or RNA of a virus particle.…”