# RKS: TRIBUTE TO DR K K AGGARWAL - The Virus in COVID-19 Needs Always TO BE Cornered & Checkmated EXPRESSLY With Mahabharat Strategy

# RKS: TRIBUTE TO DR K K AGGARWAL - 

The Virus in COVID-19 Needs Always TO BE Cornered & Checkmated EXPRESSLY With Mahabharat Strategy

1st June 2021

THE DEADLY CORONA CANNOT BE DEALT WITH KID GLOVES

Dear Reader,

The 2019-discovered novel coronavirus-2 (2019-nCoV) or SARS-CoV-2 has thus far infected near 3 crore Indians of which the unfortunate ones have been over 3 lakhs. The total number of doctor fatalities have been approximately 1000 during the pandemic, which is 0.5% of the medical professionals engaged in COVID-19 management. 

Hence, 1% of infected Indian population die of COVID-19 but, in the case of Indian doctor, 1 out of 3 SARS-CoV-2 afflicted medical professional have been pushed to their grave!! This is alarming and indeed calls for an all-out war against the pandemic-causative virus to save our fellow Dr brethren. 

THE UNFOLDING OF COVID-19 SEQUENCE OF EVENTS 

1. The SARS-CoV-2 first lodges in the nasal and mouth passages because of entry via floating droplets emanating from the carrier person with whom one interacts, sans maintaining social distancing and / or masking up. This causes symptoms.

2. When symptoms persist, or there is strong suspicion of contact with a carrier, a RT-PCR testing must be done usually after 4 days following exposure or symptoms occurrence to confirm presence of SARS-CoV-2 infection.

3. The SARS-CoV-2 remains alive seemingly up to 10 days post-entry into the human body. The virus needs to be killed efficiently and promptly by drugs and / or immune defences.

4. If the virus is not promptly killed, dangerous chemical mediators like IL-6 and NLRP3 are liberated by the defence cells of the human body in an effort to destroy the enemy SARS-CoV-2. NLRP3 is first released followed by IL-6 production. 10% of COVID-19 patients have a raised IL-6 by day 4 or 7 or 11 - an indicator of an upcoming cytokine storm syndrome (CSS). Unfortunately, at present, NLRP3 is not being estimated and hence there is no earlier 'premonition' of the CSS other than IL-6 estimation!

5. The CSS has been initiated to kill the persistent SARS-CoV-2 but the liberated IL-6 and NLRP3 cause collateral damage. Usually the damaged lungs release LDH and there is a rise in D-dimer blood concentrations, besides higher serum ferritin levels - all of these are markers to indicate CSS.

6. High D-dimer values could predict COVID-19 disease severity, lung complications ads well as blood clot formation potential even before these consequences occur.

7. If there is recovery because of appropriate and effective antiviral drugs, the dead SARS-CoV-2 RNA continues to remain in cells and could be detectable by RT-PCR even 1-2 months after the infection! (This is a false positive RT-PCR test.)

Thus, the aim has to be to kill the SARS-CoV-2 before the body's defence cells kick-starts the CSS in an effort to eliminate the virus. It is important to remember that the virus is dead in less than 10-14 days but the consequences of critical condition in hospitalised patient and fatalities are all the outcome of the already initiated CSS - the virus is no-way in the picture at that point of time!

TIME FOR MEDICAL MAHABHARAT

Not only our dear patients but we as doctors need to protect our right to life. This SARS-CoV-2 just cannot be allowed to overwhelm us and render us helpless and push us in dire striates. The need of the hour is not to be reactive but proactive. After all, as stated, one out of every 3 doctors with COVID-19 disease can have a catastrophic ending. 

A high blood CRP, which will invariably rise in all patients in 2-3 days post SARS-CoV-2 infection, can only re-confirm COVID-19 status in a positively RT-PCR tested patient. CRP values can guide regarding the severity of infection, and in no way can assist in personalising a complete drug regimen. What is more important, once positive RT-PCR and an abnormal high CRP are detected, is:

# Kill the virus with specific antivirals - so that the deadly CSS waves initiating chemical mediators are NOT generated.

# Kill the virus decisively with combination of antivirals - depending upon the severity should be the choice of specific antivirals.

# Prevent and, if necessary, tackle the COVID-19 - associated disasters with appropriate preventive regimens - when IL-6 and associated complication markers indicate possible onset of CSS.

Do not hesitate to start antivirals promptly: it could be a single agent or 2 drugs; or it could be tablets or injection (as per patient condition). The other treatment measures are secondary and complimentary.

WHICH ANTIVIRALS & WHY?

A little information on SARS-CoV-2 mechanism in thriving and causing infection would be enlightening. The 2019-CoV-2 has:

1. Structural proteins: M, E & N proteins

2. Host cell docking protein: S protein

In addition to the above, there are accessory proteins and an enzyme called RNA-dependent RNA polymerase (RdRp) which is essential for RNA replication. For the virus to be infective the S protein needs to bind with corresponding S protein ligand (docking point) present on host cell; similarly RdRp needs to interact with RdRp ligand of human cell for facilitating viral replication.

Thus, for antivirals to beneficially prevent the SARS-CoV-2 from infecting and multiplying, the S protein and the RdRp as well as their respective ligands must be inhibited. The result of blocking docking (of the S protein / RdRp of SARS-CoV-2 as well as the interacting respective ligands as MolDock score.

Higher the negative value better is the inhibitory action and more superior is the outcome of antiviral drug. Doxycycline has a MolDock score of -115.46. 

Since ivermectin has higher MolDock score than doxycycline it should be preferred in combination with favipiravir as far as swallowing antiviral pills are concerned. Why combine the latter two when favipiravir is weaker? This is because ivermectin acts on 4 amino acids (threonine, isoleucine, glutamic acid & asparagine) whilst favipiravir has unique binding action on arginine which compliments that of ivermectin. Injection of remdesivir is more suitable for the severe COVID-19 patients and those who are hospitalised.

WHY YET FAVIPIRAVIR - A Weak MolDock Scorer?

Furin is a widespread enzyme in the body, potentially granting SARS-CoV-2 countless opportunities to infect cells. One cannot, in fact, live without possessing furin enzyme! Inhibiting furin is a more beneficial mechanism than spike protein S blocking.

In order to invade the body, the spike of SARS-CoV-2 must first be snipped at a specific point by the furin protease enzyme following which the virus can then latch onto a cell’s ACE2 receptor to thereby cause infection. The spike protein as well as the SARS-CoV-2 docking site on the cell have an amino acid sequence - arginine-arginine-alanine-arginine. 

Favipirar (as tablets) and remdesivir (as injection) both inhibit furin because of binding to arginine (unlike ivermectin) but remdesivir is stronger in its action. However, when antiviral tablets are necessitated favipiravir is preferable since it has higher affinity than ritonair and lopinavir for furin enzyme as compared to S protein and RdRp and their corresponding ligands. Thus, there is always an implied and urgent necessity to advocate a combination of ivermectin with favipiravir in positively tested RT-PCR patients.

CONCLUSION

Favipiravir or remdesivir, when paired with doxycycline or ivermectin, can substantially and rapidly clear SARS-CoV-2 from nasal secretions if it was started relatively early (day 1) or latest by day 7 of confirmed COVID-19 infection. If this antiviral is given within the first few hours of infection, then the SARS-CoV-2 virus is possibly cleared in 7 days sans complications!

For prevention of CSS, corticosteroids can be initiated by day 5, or earlier if pulmonary symptoms are present or co-morbidities co-exist, in a COVID-19 sufferer. Abnormally high D-dimer values naturally signal institution of anti-clotting medication.

Thus, to defeat the SARS-CoV-2 in fighting the COVID-19 the Mahabharat - like forces are:

1. Yudhistira - The advising Dr

2. Arjuna - The sharp-shooter antiviral 

3. Bhima - The bull-dozer corticosteroid

4. Nakula - The immunity supporters - Vitamins C & D, zinc (acetate, gluconate)

5. Sahadeva - The strategist anticoagulant

We doctors need to win COVID-19 war without ultimate sacrifice. Why risk and leave the outcome to destiny and good wishes and faith. We must ensure no loose ends are left and all gaps filled. Under the guidance of one of our trusted but more aggressive Dr guru we must adopt the Mahabharat strategy. 

REMEMBERING DR K K AGGARWAL

We have paid the price with over 1,000 of our colleagues falling in the battle, including our beloved physician and cardiologist Dr Krishan Kumar Aggarwal who was President of Confederation of Medical Association of Asia and Oceania (CMAAO) as well as Heart Care Foundation of India (HCFI) & Past National President of Indian Medical Association (IMA) - besides being a Padma Shri and B C Roy National award recipient. 

My tryst with Dr K K Aggarwal was first in the month of August 2020 as we planned a special one-hour session on CSS for his MedTalks series. This was possibly the first time ever, as Editor-in-Chief of MedTalks Dr K K Aggarwal facilitated an elaborate PowerPoint presentation, at my request, on his 7 pm 11th September 2020 show titled - Chemical Mediators Causing Cytokine Storm In Viral Infections: MedTalks with Dr K K Aggarwal. He was possibly the first medical professional with whom I had willingly ever given my presentation knowing fully well that Dr K K Aggarwal will be most enthusiastic in wide-spreading my data on a broader-based platform so as to benefit both Indian and overseas doctors. The very next day I was invited by Dr K K Aggarwal to explain a few of my slides in a COVID-19 - related meeting of CMAAO and I will always be grateful for this opportunity.

Dr K K Aggarwal had immense following of his thrice a day YouTube video talks uploads pertaining to different aspects of corona pandemic. His crystal clear views on coronavirus pandemic, and lucid presentation of the same, enabled percolation of COVID-19 knowledge even to the layman. He will forever be remembered. 🙏

The second wave of COVID-19 is scary because of its 80-90% virus transmissibility rate from contacts in comparison to 30-40% in first wave! Most health workers would not seemingly be able to escape getting infected with SARS-CoV-2 - preventive measures and vaccination notwithstanding! Be mind-tuned to hit hard the virus if it attacks. We cannot afford to lose another luminary from amongst medicos.

God BLESS the warring Doctors.

DR R K SANGHAVI

Prophesied Enabler

Experience & Expertise: Clinician & Healthcare Industry Adviser