Can Papain in Papaya Destroy the SARS-CoV-2 Spike Protein?

 I was eating a slice of papaya for dinner last night when suddenly a thought ran through my mind: if the enzyme papain, which is a proteolytic enzyme that breaks down protein, can inhibit the pathogenicity of SARS-CoV-2 virus?

 

This enzyme is found abundantly in the leaves, and ‘milk’ of raw papayas.Papain is a digestive enzyme that  triggers off  an allergen-like inflammatory response and activating the immune bodiesIts pharmacodynamics (mode of action), it does this by  releasing  neutrophils, mast cells, and CD3-positive cells and CCL8-positive and also the induction of a TH2-biased antibody response. In short, it activates the immune system.

 

It was shown in vitro (in lab studies) papain resulted in the breakdown of proteins by digesting the tight junctions of primary human keratinocytes that maintain the epithelial barrier integrity.

 

These tight junction proteins include zonula occludens-1, claudin-4, and occludinIn simple language it breaks down the shorter peptide or longer polypeptide chains of amino acids of the protein. The amino acids in a peptide are connected to one another in a sequence by bonds called peptide bonds. . 

 

These chains of amino acids that make up literally any protein may cause an impenetrable barrier for drugs to act. Hence it may also be possible papain, or may not be able to penetrate and break down the peptide bonds of the SARS-CoV-2 spike protein.

However papain cannot digest our own human proteins just like gastric juices cannot digest our stomach.

 

Pepsinin the stomach is the main gastric enzyme. It is produced by the stomach cells called "chief cells" in its inactive form pepsinogen, which is a zymogen. 

 

 Pepsinogen is then activated by the stomach acid into its active form, pepsin. Pepsin breaks down the protein in the food into smaller particles, such as peptide fragments and amino acids. Protein digestion, therefore, primarily starts in the stomach, but it cannot digest its own stomach protein

 

So does other protein-digesting enzymes in the intestines cannot digest or break down its intestinal proteins such as in the pancreatic juice from its ductal and acinar cells, containing trypsinogen, which is an inactive(zymogenic) protease that, once activated in the duodenum into trypsin, breaks down proteins at the basic amino acids. Trypsinogen is activated via the duodenal enzyme enterokinase into its activeform trypsin. 

 

Chymotrypsinogen, which is an inactive (zymogenic) protease that, once activated by duodenal enterokinase, turns into chymotrypsin and breaks down proteins at their aromatic amino acids. Chymotrypsinogen can also be activated by trypsin.

 

Other proteolytic enzymes in the pancreatic juice are carboxypeptidase, which is a protease that takes off the terminal amino acid group from a protein.

 

Several elastases that degrade the protein elastin and some other proteolytic enzymes do not attack its own body proteins

 

However in the case of papain it specifically acts on foreign proteins. In fact it breaks down the elastic bond holding the muscle fibers together, and is used as a meat tenderizer

However, what I am unsure is, whether or not this mode of action so far as we know exhibit the same for spike proteins of this SARS-CoV-2 in vitro (outside the body) and in vivo (inside the body when taken orally)? This is a very crucial question I am unable to answer right now.

 

In simple language, can papain break down or digest the amino acid (peptide) chains of the spike proteins that is the main cause of its pathogenicity and hence may render this virus completely non-pathogenic?This is the question I do not know the answer.

 

Just like Ivermectin, it was accidentally discovered by Australian scientists that it could inhibit in vitro coronavirus replication in large doses.



So in the same thinking (at least in theory), whether or not papain can be used to break down the chain of this spike protein?

This is a very crucial question I suddenly asked myself when I ate a slice of papaya for dinner last night.

However, on second thought I do not think we can use papaya enzymes against Covid-19 or the SARS-CoV-2 virus since they are airborne diseases tranmitted by respiratory droplets containing the viruses through coughs and sneezes and is not a gastrointerstinal infections where we can ingest orally some specific anti-virus enzymes or an agent into the gastrointestinal tract. That is why 

 

In scientific discoveries sometimes it is accidental rather than based on the extension of previous known knowledge.

 

We call this unplanned and accidental discovery as "serendipity"

I learned this term when I was doing a postdoctoral course at Cambridge. 

For instance, Issac Newton (1642-1727) discovered gravity during the time in 1665–1666, when the bubonic plague struck England, just like now in 2019 - 2021when this Covid-19 pandemic strikes.

  

His discovery of gravity was through serendipity rather than planned by wondering why an apple should  fall.

So was penicillin discovered accidentally  by Sir Alexander Fleming (1881–1955) in September 28, 1928.   

 

As far as I know in Science there are at least 20 discoveries made through serendipity. They were all mainly through sudden analytical thinking rather than deliberate experimental work.

 

I am not claiming that papase which is such a very cheap enzyme  marketed as  Beazyme and is available so readily in any pharmacy is the final and real solution to Covid management.

 

Please, I do not claim that, and I shall not. I do not know, as I am now retired from any medical research. I would like to leave this question to the younger researchers to find out.It was just my  sudden thought when I took some papaya (contains papain) for dinner last night



What we need to do is to study the action of this proteolytic enzyme in cell culture in vitro, and once it works like Ivermectin in lab cell cultures, we can then put this to test clinically by taken high doses of papase (normal dose for papain for inflammation is 2 tab qid (8 tabs spread out over 24 hours.

 

It may work, I do not know for sure? It may also not work, I am unsure?It all depends on the initial vitro study, and then if it does, we also need to understand its pharmacokinetics (time of drug absorption, distribution, retention,metabolism, and excretion) once taken orally.

 

It may not even be able to penetrate into the lung tissues where it is most needed. I do not know?

Give this a thought. It's just my contribution in medicine and science for my younger counterpart to think over.

 

In medicine, anything is possible. We do not depend on textbooks of medicine or what big drug companies dictate to us and poison our mindset. We use our brains to think intelligently not what drug companies insist

 

Worth a try to the best of my knowledge in pharmacology (mode of action of drugs on the  body) and pharmacognosy (Pharmacognosy (study of plants or other natural sources, their physical, chemical, biochemical and biological properties) as a possible source of drugs.


It could be a case of serendipity while eating a papaya. I really do not know with certainty.

 

Best Wishes

Lim ju boo