My proposal for Covid 19





POSSIBLE preventive measure (not proven) and is not a cure: switch your mouthwash (Dr. Dhruv BDS, Dip, MS USA)
Betadine mouthwash. Recommended to use this for 15 seconds morning and night, and when coming home from outside. It might eliminate the coronavirus in the oral cavity (mouth) and the remaining will be eliminated by the gastric juices in the stomach. DO NOT Use this mouthwash for more than 14 days. People with certain conditions don’t use (read before use in reference link 3 given below.)This conclusion is based on the reference articles
References
1. Transmission routes of 2019-nCoV and controls in dental practice Xian Peng1, Xin Xu1, Yuqing Li1, Lei Cheng1, Xuedong Zhou1 and Biao Ren 1
2. In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens Maren Eggers, Torsten Koburger-Janssen, [...], and Juergen Zorn
(Do not use Betadine Gargle and Mouthwash 10mg/ml Oral Solution: - if you are allergic (hypersensitive) to povidone-iodine or any of the other ingredients listed - if you currently have or have ever had a thyroid problem, including swelling (nodular colloid goiter, endemic goiter or Hashimoto’s thyroiditis), as using Betadine Gargle and Mouthwash in these circumstances can further affect the function of your thyroid - if you are currently having lithium therapy for depression as this type of medicine can interact with Betadine Gargle and Mouthwash to affect the function of your thyroid - on children of 6 years and under.)
Follow up article:
Prevention of tooth decay and antiviral effect: lifestyle change Dr. Dhruv BDS, Dip, MS USA
As said in our preventive and community dentistry books, oral health is a reflection of our overall health and shown by my present mentor, Dr. Achuth Baliga 12 years ago at Manipal Hospital how a patient’s medical problem is reflected in the palate of the mouth for a kidney patient. So, we need to take care of the gateway to the coronavirus, the mouth from infection(Oronasal passage). Once, the betadine mouthwash has been used for 14 days. So, the iodine doesn’t get absorbed in the body. Switch to Listerine mouthwash as the coronavirus situation improves. This could be used as regular prophylaxis (daily use, morning and night after brushing your teeth in bass technique i.e., circular motions) to prevent dental decay (betadine also, has this anti-cariogenic i.e., anti decay effect in it, so, initially using it as a mouthwash has benefits) along with its antiviral effect. No proven effect on coronavirus as yet. Chlorhex mouthwash which is known to be a gold standard could be also, used as it acts against the enveloped viruses. Since few of the brands of chlorhex cause brown stains use it as and when recommended by your doctor (dentist in this case)
No financial conflict of interest, for this article. Dr. Ashita scientific engagement manager of Johnson and Johnson Ora care brand of Listerine gave me the references for this article.
References
1. Efficacy of Listerine Antiseptic in Reducing Viral Contamination of Saliva Timothy F Meiller et al. J Clin Periodontol. Apr 2005
2. Potentials of Mouthwashes in Disinfecting Cariogenic Bacteria and Biofilms Leading to Inhibition of Caries Takehiro Oyanagi,a Junji Tagami,a,b and Khairul Matina,c,*
To summarise:
1. Betadine mouthwash as the 1st line of action for the first 14 days during the peak of the coronavirus situation
2. Listerine mouthwash as the 2nd line of action after 14 days once, coronavirus situation improves and finally,
3. Chlorhex mouthwash (as per the recommendation of your dentist) is the initial line of action for periodontal(gum) conditions except in surgical cases, betadine must be continued as the first line of action, once, coronavirus times completely dissipates. None of this has any proof yet against coronavirus.
This is only my humble opinion to help out in these coronavirus times. Take care of yourself and stay safe. This is in addition to precautions like social distancing, etc, which the governments have been mentioning. Someone having the facilities that can test it out is my humble request.

Prevention or treatment or both of covid 19 by Dr. Dhruv BDS, Dip, MS USA  

This is a small idea of mine hypothesis does the lipid rafts or lipid micro domains of the ACE2 receptor and the lipid surrounding the virus specific to each other (picture above)

Rationale: This is one additional information I found out which might be useful
This data from the reference below suggest that lipid metabolism regulation is a common and druggable target for coronavirus infection

Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357182/

Specific aim 1: I would like to know, if the Covid 19 lipid envelope is specific to it and a lab which would shed light on these experiments 
Specific aim 2: Can an antibody target the lipid of the virus for prevention of covid 19
Specific aim 3: Does the lipid of the virus and lipid raft of the ACE2 receptor interact to unfold the signaling pathway downstream for treatment of covid 19 and drug inhibiting mechanism or downstream interactions 
Experiment 1 to 3 for solution: to check specificity then, any antibodies for lipid of virus. And any drug/s inhibiting mechanism or downstream

Cofactors in Coronavirus Entry
January 2011 Ana Shulla University of Chicago 
https://www.researchgate.net/publication/254615633_Cofactors_in_Coronavirus_Entry
As mentioned in reference above of the findings, which are lipid adducts anchoring S protein into virus membranes important for protein folding that culminates into membrane fusion

ACE2 is a known lipid raft-embedded protein, and TMPRSS2 is set apart from other TTSPs by its longer, potentially palmitoylated 84-residue cytoplasmic tail, which may confer positioning into lipid rafts. The SARS-CoV-susceptible cell may be defined by tendencies of ACE2 and TMPRSS2 to congregate together. https://jvi.asm.org/content/85/2/873

Rationale: Lipid raft is an important element for the cellular entry of some viruses, including coronavirus infectious bronchitis virus (IBV)
the drug-mediated depletion of lipid rafts in Vero cells before IBV attachment significantly reduced the expression of viral structural proteins, suggesting that drug treatment impaired the attachment of IBV to the cell surface. 

The Important Role of Lipid Raft-Mediated Attachment in the Infection of Cultured Cells by Coronavirus Infectious Bronchitis Virus Beaudette Strain

What is Trump claiming as a cure?

From the email to me from a researcher from my mentor in research’s team
“Additionally, you can consider Phospholipases A2 inhibitors ( specially cytosolic PLA2) which a very crucial rate limiting enzyme  in the lipid metabolism. Example, antimalarial drug quinacrine ( structurally related to chloroquine) is known PLA2 inhibitors.”

That supports my base idea.
Specific aim 4: Scientifically prove the mechanism of action of chloroquine, which might be to check if it indeed would treat covid 19 at a molecular level, which might be immediately useful to people or is there some modifications which might be required to it, which will give a more effective preventive or treatment or both. 
Specific aim 5: with knowing the mechanism of action can additional medicines be added to make it more effective giving a result or results earlier like a vaccine 

Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection
https://www.sciencedirect.com/science/article/pii/S0924857920301102?via%3Dihub

Here, out of excerpt out of the above reference, I’m trying to show the connection of lipid raft and mechanism of action I’m proposing with chloroquine 
chloroquine (CLQ), one of the drugs currently under investigation for SARS-CoV-2 treatment, binds sialic acids and gangliosides with high affinity. A new type of ganglioside-binding domain at the tip of the N-terminal domain of the SARS-CoV-2 S protein was identified. This domain (111–158), which is fully conserved among clinical isolates worldwide, may improve attachment of the virus to LIPIDS RAFTS and facilitate contact with the ACE-2 receptor. This study showed that, in the presence of CLQ [or its more active derivative, hydroxychloroquine (CLQ-OH)], the viral S protein is no longer able to bind gangliosides.

Rationale: Chloroquine one mechanism of action
acidification at the surface of the cell membrane inhibiting fusion of the virus,
https://www.elsevier.com/__data/assets/pdf_file/0007/988648/COVID-19-Drug-Therapy_Mar-2020.pdf
Above action supporting my hypothesis 

The evaluation found studies showing potentially dangerous changes in the electrical patterns of some patients' hearts, as well as gastrointestinal side effects. It acknowledged there is a "knowledge gap" about what is known, making clinical trials crucial.
ELIZABETH WEISE | USA TODAY | 6:12 pm EDT April 15, 2020

Theoretically I believe chloroquine will work as it inhibits the mechanism of action proposed in my hypothesis proposed here. 
So, What is the prescribed safe dosage of chloroquine that works to treat covid 19 in humans?
(As per one of my dental patients, who is a doctor who was treating covid 19 patients in Karnataka, state of India)

Prophylaxis: Hydroxychloroquine (HCQ) 400mg BD (i.e., twice a day) for first day and then, 400mg, OD (once a week) for 7 weeks for healthcare workers
Treatment (not on ventilator) +ve covid 19 patients: quarantine three weeks, HCQ 400mg BD 1st day and HCQ 400 mg OD for 10 days
Treatment for covid 19 +ve patients: ventilator setting arterial blood gas, HCQ not given (I.V toxic at required level), antiviral: tamiflu, indinavir and Ritonavir
Experiment 4: Is there a way to get an i.v level of HCQ that works? All this needs clinical trials 
As per my mentor in research, “HCQ plus standard of care was still better than standard of care alone 

So it’s helping inflammatory response for sure, although viral load reduction is not there” 
https://www.google.co.in/amp/s/www.thehindu.com/sci-tech/science/hydroxychloroquine-does-not-reduce-viral-load-randomised-trial-shows/article31375420.ece/amp/

Hydroxychloroquine reduces viral load in COVID-19 patients
https://www.virology.ws/2020/03/19/hydroxychloroquine-reduces-viral-load-and-symptoms-in-covid-19-patients/

Rationale: Another job of the acquired immune system is to stand-down the innate immune system; until that’s done the innate immune response will keep increasing as the virus replicates and spreads. Part of the innate immune response is to cause ‘inflammation’. That is useful in containing the virus early in an infection but can result in widespread damage of uninfected tissue (we call this a ‘bystander effect’) if it becomes too large and uncontrolled, a situation named ‘cytokine storm’ when it was first seen with SARS and avian influenza H5N1. It is difficult to manage clinically, requiring intensive care and treatment and carries with it high risk of death.

How can we explain these discrepancies and how should antimalarial drugs be used in the clinical management of patients in the ICU with severe COVID-19?

So, a small thought of HCQ plus standard of care treatment for the emergency, bringing me to the vaccine

Rationale: Scientists generate the mRNA in the lab and, rather than directly injecting SARS-CoV-2 into patients, instead introduce this mRNA. By design, the vaccine should prompt human cells to build proteins found on the virus' surface and thus trigger a protective immune response against the coronavirus.

Experiment 5: Can this be done, for the lipid or the virus? 
Is anyone, doing it, for a covid 19 vaccines?
Brings me back to the original question of my hypothesis is the lipid specific to the virus?

Alternate strategies: if all this doesn’t work then, look for antibodies against the lipid of the virus. If, the lipid not specific. Then, look for antibiotics/drugs against the proposed mechanism of action. If, the hypothesis is not true and no interaction between specific lipids of virus & cells, then, to look into the proteins in the lipid rafts interacting with the virus, like TMPRSS2 

Result is to find out a vaccine for covid 19 with the specificity of the lipid of the virus and emergency treatment via clinical trials for HCQ which will give a complete solution for covid 19, without ignoring the population which are covid 19 positive and not on ventilator by management of symptoms from known medicines, by inhibiting mechanism proposed. 

Significance: this is a pandemic or world wide crisis or emergency originating from China, which needs to be tackled by everyone. So, primarily as a dentist with a background in research in America of four years with two & a half years in drug development this is what idea I can come up with in life to help everyone. You too suggest ideas which can help humanity

Research design
Method
Experiment to check lipid is specific to virus and isolate the lipid of the virus

Lipid composition of viral envelope of three strains of influenza virus - not all viruses created equal
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593503/

There’s a flaw in my idea, if the lipid of the virus is derived from the previous host then, lipid of the virus won’t be specific to the virus and the lipid will have something in common to the lipid in the body. So, there’s a very high chance the lipid is not specific to the virus 

Then, the next step we would have to observe if, the lipid of the virus interacts with lipid raft next to ACE2 receptor, which is my original idea and hypothesis that will make it a longer process to find a drug with this target to prevent the interaction, instead of directly injecting the lipid of the virus for an antibody, 

If lipid specific of virus. Then faster and easier we can directly inject the lipid of the virus as originally planned, which will help humanity faster while the interaction can be checked for treatment

This flaw in my idea true or not will still have to be checked since, it’s a crucial step for a faster vaccine and my hypothesis. So, a mass spectrometry would be required

As commented before, specific lipids located in the viral particles can also play a role on viral entry of enveloped viruses [8], including 'those located in' lipid rafts [49-51]. Vaccinia virus provides another example of the relationships between lipids located on the viral particle and viral entry. In this case, the presence of exposed phosphatidylserine in the viral envelope is critical to induce blebs on cellular membrane that promote virus internalization [23].

This process is assisted by viral proteins termed fusion proteins, and results in lipid mixing between the viral envelope and the target cellular membrane [63-66].

Differences on the lipid composition of the viral membranes may reflect their different origin.

Despite that the lipid content of enveloped viruses has been studied for decades [153-155], quantitative analyses of viral lipidomes (the entire content of lipids) at the individual molecular species level have not been possible until recently, by means of the improvement of mass spectrometry [3,139].

In other cases, major differences in lipid content between viral envelopes and host cell membranes have been found. 

https://www.intechopen.com/books/lipid-metabolism/lipid-involvement-in-viral-infections-present-and-future-perspectives-for-the-design-of-antiviral-st


We also, have to observe the current scenario if a vaccine or treatment or both have been found before proceeding with the experiments like in the link below by the serum institute of India, which are starting production

https://www.businesstoday.in/opinion/interviews/if-trials-are-successful-serum-institute-to-sell-coronavirus-vaccines-for-rs-1000-says-ceo-adar-poonawalla/story/402301.html


Then, if the preliminary experiment of a lipid in virus is specific to it then, a simple experiment as explained by Bill Gates in the video below, for a vaccine 

https://www.facebook.com/100533958292420/posts/120210279658121/?d=n

In simple words, the specific lipid found in the virus injected to produce antibodies against the novel Coronavirus
Animal trials (mice) and then, humans


Alternate strategies already told, which is the specific lipid on the lipid raft next to the ACE2 receptor and prevent its interaction with the lipid envelope of the novel Coronavirus 


I hope you contribute to check if this concept is true or false of my idea of a hypothesis. Thank you in advance for supporting my concept


As per Rebecca Dutch of University of Kentucky,
The differences are in the ratio of the lipids present, not in the presence of lipids in viral envelopes that are unique.

As per me former student of University of Louisville,
This is a small idea of mine hypothesis does the lipid rafts or lipid micro domains of the ACE2 receptor and the lipid surrounding the virus specific to each other. This is my original idea from where my concept originated so, will the difference in ratio of lipids in the host and virus help in prevention of the interaction if  We find a way to block it ?

Question can a difference in ratio of lipids of virus from host instigate an antibody reaction which is not harmful to the body, preventing the interaction of the lipid raft next to ACE2 receptor and lipid envelope of virus?

Two simple experiments 

1. Isolate the different ratio of lipid of virus from host
2. Inject virus lipid in body to check if no adverse affect of antibody reaction preventing interaction with body cells

Reasoning 
1. Different ratio of lipid leads to different function?

https://en.m.wikipedia.org/wiki/Lipid_bilayer

2. As per Biju George of Indian institute of science,

Lipids are actually very poor immunogen . The will generate very poor immune response . Which is insufficient to eliminate the virus. 

So, as per me
The poor immunogenicity response of lipids won’t harm body 

The liposomal virus delivery system will be interrupted by the antibody, therefore working as a vaccine and solving the problem completely 


These experiments must be looked into to check its safety and efficacy

Is this concept okay? In two steps, the vaccine could then be made (a) Isolate the different ratio of lipid of virus from host (b) Inject virus lipid in body to check if no adverse affect of antibody reaction preventing interaction with body cells

Like soap destroys the lipid envelope, the same is what we are trying to achieve by the antibodies of the body

https://gulfnews.com/lifestyle/health-fitness/covid-19-how-soap-annihilates-a-virus-1.1585140805837?slide=1


Rationale, as per few of the papers and information provided by Biju George PhD from Indian Institute of Science. It’s seen that when there is a cell membrane alteration in pathological conditions, Anti lipid antibodies are produced. Budding of enveloped viruses in the processes may alter the surface smoothness, molecular composition, etc. also the composition and function varies with the uptake in the cells. cholesterol specific antibodies might activate certain system like the complement and phagocyctic systems to eliminate the virus particles.
It’s also seen that IgG anti lipid antibodies are produced during malaria and hydroxychloroquine known to also, affect the lipid metabolism in Covid 19, etc. IgG antibodies are seen against lipids in different conditions and IgG anti cholesterol antibodies have been detected in viral infections. Affinity maturation of antibodies against lipids are seen with time. (Long term) memory and normal B cells also seen against lipids. Therefore, it’s important to understand the antibodies against lipid antigens in case of infections wherein the lipid envelope could be used as a target for antibodies to form against novel Coronavirus 

1. Novel anti-cholesterol monoclonal immunoglobulin G antibodies as probes and potential modulators of membrane raft-dependent immune functions Adrienn Bı´ro´ † La´szlo´ Cervenak,1,† Andrea Balogh,1,§ Andra´s Lo´´rincz,§ Katalin Uray, Anna Horva´th, La´szlo´ Romics, Ja´nos Matko´ ,George Fu¨st,and Glo´ ria La´szlo´ . Journal of lipid research 2006

2. anti lipid IgG antibodies are produced via germinal centers in a murine model resembling  human lupus. Carlos Wong-Baeza, Albany Reséndiz-Mora2, Luis Donis-Maturano Isabel Wong-Baeza, Luz Zárate-Neira2, Juan Carlos Yam-Puc, Juana Calderón-Amador Yolanda Medina4, Carlos Wong2, Isabel Baeza2 and Leopoldo Flores-Romo. Fronties in immunology 2016


3. Membrane lipid composition and cellular function Arthur A. Spector and Mark A. Yorek Journal of Lipid research 1985

Saliva Covid 19


Collect the saliva and isolate the lipid of the virus from there then, inject it for the antibodies to form


Contributors 
Family and friends
Professors, Researcher and Doctors of University of Louisville and India
University of Kentucky and Indian institute of Science 
World Wide Web 


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