CMAAO Coronavirus Facts and Myth Buster: Antiviral Drugs |
Editorial
eMediNexus Coverage from: 
CMAAO Coronavirus Facts and Myth Buster: Antiviral Drugs
Dr KK Aggarwal,  18 September 2020
Coronavirus Live Count Map India

remove_red_eye 1997 Views
#Multispeciality

1 Read Comments                

With input from Dr Monica Vasudev

1084:   Update on COVID-19

IMA-CMAAO Webinar on “Antiviral drugs”

12th September 2020: 4-5pm

Participants: Dr KK Aggarwal, President CMAAO, Dr RV Asokan, Hony Secretary General IMA, Dr Ramesh K Datta, Hony Finance Secretary IMA, Dr Jayakrishnan Alapet,

Dr Brijendra Prakash, Dr S Sharma

Faculty: Dr KK Sharma, Advisor, National Academy of Medical Sciences

Former Head, Dept. of Pharmacology, UCMS

Key points from the discussion

  • When virus enters the cell, it is taken up and is killed by the macrophages. No antibodies are formed, the patient is asymptomatic.
  • In some persons, the virus enters the blood → dendritic cells in thymus →T cells and then to B cells and produces IgG and IgM. The patient is asymptomatic, but antibodies are formed.
  • In a third scenario, the cells produce IFN-1 on Day 1, which initiates neutrophils, NK cells and monocytes. The NK cells and monocytes produce IFN-γ, which kills the virus as do the neutrophils. The patient is asymptomatic because of adequate immunity.
  • Another scenario, the IFN-γ will produce TNF-α, which causes inflammation. The person will be symptomatic on Day 1 (fever, diarrhea, headache, rash, loss of smell/taste).
  • If the immunity is inadequate, the virus is not killed. The cells do not form IFN-1 in such a situation, alternate pathway opens up on Day 3. Macrophages produce NLRP3, which produces IL-1β and IL-18. IL-1β increases ferritin levels, glucuronidase causing tissue damage. IL-18 adds to the inflammation. Cells through the cellular dendritic cells produce Th1 cells, which produce IL-6 (formed on Day 3), TNF-α and IL-8. IL-6 causes clot formation, TNF-α (formed on Day 1), IL-8 and IL-1β (formed on Day 3), cause inflammation.
  • Antiviral drugs act at different levels. For antiviral drugs to be active, they need to be in the triphosphate form; they may be in triphosphate form or may use the host phosphorylation enzyme to convert to this form.
  • Remdesivir is an RNA-dependent RNA polymerase (RdRp) inhibitor. It is DCGI approved for severe COVID-19 infection. It is active in itself as it is in the triphosphate form. So, when given intravenously, it starts producing effects immediately. It does not prevent entry of the virus into the cell; it acts at the replication stage and prevents replication of the virus inside the cell.
  • Favipiravir is also an RdRp inhibitor but has weaker action than remdesivir. It is administered orally. It requires to be converted into triphosphate form;hence, it takes time to start its action. It is approved only for mild to moderate infections.
  • Oseltamivir is a synergistic agent. It is approved for flu. It is not given alone; it is given along with remdesivir or favipiravir. It synergizes activity by complementary mechanism and also inhibits replication of the virus.
  • Ribavirin is given for HIV and hepatitis C infections; it is a broad spectrum orally active drug. It can be given along with other drugs like oseltamivir (off-label use).
  • Lopinavir + ritonavir combination has been approved by the DCGI; they are weak anti-HIV drugs, which are protease inhibitors. They are also synergistic and should not be given alone. Ritonavir has anti-HIV activity by itself and it also decreases the effect of cyclo-oxygenase enzyme and reduces metabolism of lopinavir, thereby increasing its concentration.
  • Ivermectin also prevents entry of the virus into the cell; it is also weakly active inside the cell similar to remdesivir and favipiravir.
  • Doxycycline, azithromycin, teicoplanin act on the bacterial infections; they also synergize the activity of the compound with which they are given. So, they not only act against secondary infections, they also act de novo as weak antiviral agents.
  • Mefenamic acid has a good anti-inflammatory potential in COVID as it works against PLA2 enzyme, NLRP and interleukins. It is better than paracetamol.
  • Dexamethasone can be used as it is cheaper and can be given oral/IV. It is indicated for severe COVID-19 infection, especially to control cytokine storm. Steroids are anti-inflammatory agents; they inhibit PLA2 enzyme, thereby inhibiting the formation of various cytokines and inflammatory agents, including interferons, interleukins and TNF-α.
  • When virus is not replicating, it still has domains which are antigenic and can increase formation of cytokines.
  • “Long Covid” is a term, which is used for people who have recovered but are still suffering some manifestations of the infection for long periods, which are due to these viral particles (antigens).
  • Bradykinin is a slow acting peptide; its effects last for a long period of time. It is a very powerful vasodilator and increases vascular permeability. So, wherever bradykinin accumulates in the body, it will cause edema, further adding to the inflammation. Bradykinin receptor inhibitors are being developed. It’s still experimental. Methylene blue inhibits the manifestations of bradykinin at functional level.
  • Th1 cells of the thymus are proinflammatory; Th2 cells are anti-inflammatory. Th1 cells produce IL-6 (a very powerful inflammatory agent), TNF-α, IL-8.  
  • Thymosin alpha has a good potential for evaluation (thymus hormone).

 

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA

To comment on this article,
create a free account.
Sign Up to instantly read 30000+ free Articles & 1000+ Case Studies
Create Account

Already registered?

Login Now