BREAKING! Coronavirus Supplements: University Of Nesbraska-US FDA Vitro Study Shows That Bromelain From Pineapples Inhibits SARS-CoV-2 In Vero E6 Cells

Coronavirus Supplements: Researchers from the University of Nebraska Medical Center and Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring have demonstrated in vitro studies that bromelain extracted from pineapples is able to inhibit the SARS-CoV-2 coronavirus in Vero E6 cells via a  multitude of ways.


 
The study findings are published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2020.09.16.297366v1
 
Thailand Medical News would like to warn readers that before anyone starts rushing out to the supermarkets to hoard on pineapples or start ordering bromelain supplements online to dose themselves or worse start binging on Pina Coladas as an excuse, kindly note that the study findings are from a vitro study only.
 
To date molecular docking studies and vitro studies have turned up hundreds of potential SARS-CoV-2 inhibitors but whether they work in vivo studies with animal models or better still in humans clinical trials is altogether another issue and till drugs, supplements or herbs pass human observational and controlled randomized clinical trials, nothing is deemed as a sure thing.
 
The study results of this recent research endeavor from the United States indicate that bromelain or bromelain rich pineapple stem may be utilized as an antiviral agent against coronavirus disease (COVID-19), but also for potential future coronavirus outbreaks.
 
A previous study had showed that bromelain was able to destroy certain viral proteins in the human respiratory coronavirus OC43. https://www.sciencedirect.com/science/article/abs/pii/0168170286900134?via%3Dihub
 
The main initial interaction between Transmembrane Serine Protease 2 (TMPRSS2), primed spike glycoprotein (S-protein), and host cell receptor angiotensin-converting enzyme 2 (ACE-2) is a pre-requisite for cell entry and COVID-19 pathogenesis.
 
Repurposing existing drugs or chemical compounds from supplements, herbs or develop new antivirals against SARS-CoV-2 is still a way forward either by using strategies to disrupt the binding process or by destroying viral proteins essential for replication.
 
Bromelain - a dietary supplement isolated from pineapple stem used to treat patients with pain, inflammation, and thrombosis was explored for a multitude of reasons and besides certain initial computational studies showing its molecular docking properties against the SARS-CoV-2 genome.
 
Past studies had shown that bromelain was able to destroy the viral envelopes of viruses like HIV, HPV and Hepatitis and halt virus replication but it was never further explored as a therapeutic agent. https://medwelljournals.com/abstract/?doi=jeasci.2018.3125.3130 and
https://publications.inschool.id/index.php/icash/article/view/400
 
The hypothesis of using the protease enzymes (which are almost similar to enzyme pepsin in terms of properties)in bromelain as a antiviral candidate against the SARS-CoV-2 coronavirus was tackled by researchers from the University of Nebraska Medical Center and Center for Biologics Evaluation and Research (CBER) in Silver Spring in the United States, with rather interesting findings.
 
As ACE-2 and TMPRSS2 are full of cysteine residues that establish disulfide bonds to support the protein structure, this research group primarily appraised the effect of bromelain (which is a cysteine protease) on ACE-2 and TMPRSS2 expression.
 
While the full-length genome sequences of 45 SARS-CoV-2 isolates were analyzed in-depth, the African green monkey kidney epithelial cells (Vero E6) was chosen as the primary cell line utilized in this study.
 
The study team cloned and subsequently expressed SARS-CoV-2 S-protein ectodomain that contains insect cell secretion signal.
 
They then determined the interaction between the purified S-Ectodomain and human recombinant ACE-2 using surface plasmon resonance technology (i.e., real-time detection of biomolecular interactions).
 
Lastly, they have expressed SARS-CoV-2 S-Ectodomain tagged with a green fluorescent protein in Tni insect cells from Trichoplusia ni (i.e., cabbage looper). Surface resonance plasmon and Luminex assay were used to reveal the purified S-Ectodomain binding to human ACE-2, as well as immunoreactivity with COVID-19 positive samples.
 
Professor Dr Prakash Radhakrishnan, corresponding author of  the study from the Eppley Institute for Research in Cancer and Allied Diseases and also from Fred & Pamela Buffett Cancer Center, both based at the University of Nebraska Medical Center told Thailand Medical News, "We demonstrated in this study  that bromelain (isolated from pineapple stem and used as a dietary supplement) treatment diminishes the expression of ACE-2 and TMPRSS2 in VeroE6 cells and dramatically lowers the expression of S-Ectodomain.”
 
Significantly the study demonstrated that bromelain decreases the expression of both ACE-2 and TMPRSS2 in a dose-dependent manner in Vero E6 cells.
 
Also, bromelain's cysteine proteolytic activity was notably higher in ACE-2 when compared to TMPRSS2.
 
Of more significance was the finding that the bromelain treatment was able to halt the interaction between S-Ectodomain and Vero E6 cells, significantly diminishing the SARS-CoV-2 infection in this cell line.
 
The study also indicated that the SARS-CoV-2 spike glycoprotein has both highly sialylated N- and O-linked glycans, and bromelain managed to cleave it.
 
A consequent loss of negatively charged sialic acid groups in the N- and O-linked glycans may cause a decreased mobility shift of S-Ectodomain.
 
The study team further added, "For the first time, our study results demonstrate that bromelain can inhibit SARS-CoV-2 infection by targeting all three host ACE-2 and TMPRSS2, and SARS-CoV-2 S-proteins.”


Bromelain inhibits / cleaves the expression of ACE-2 and TMPRSS2, it cleaves / degrades
SARS-CoV-2 spike protein and inhibits S-Ectodomain binding and SARS-CoV-2 infection.
 
Past studies have demonstrated that bromelain can be utilized to treat patients with inflammation and pain and that the compound is well absorbed and with prolonged biological activity. All of these advantages and it safety issues can be exploited when treating patients with COVID-19.
 
The research team concludes that either bromelain or bromelain rich pineapple stem represents a viable option as an antiviral for treating not only COVID-19 but also potential future outbreaks of other coronaviruses.
 
As the US FDA was involved in this study, we have no updates as of press time if Trump or any of his relatives or cronies had invested in pineapple farms in the last few months. But one thing we do know is that the pineapple farmers in Thailand are going to be happy with these study findings after having to endure an economic slump as a result of declining demand for their crops.
 
Also for those still persistent to start ordering bromelain supplements online or going out to buy them, note to only go for credible brands and avoid fake products that are being sold online on various platforms and also note that the GNC brand of supplements and the company is now owned by Chinese from mainland China, where the first outbreak of COVID-19 started and spread to the rest of the World.
 
For more on Coronavirus Supplements, keep on logging to Thailand Medical News.