As of July 2021, SARS -CoV2 has claimed the lives of 4 million people who had contracted the deadly respiratory virus. Vaccines serve as a prime contributor in eradicating the coronavirus along with few drugs. Vaccines drives are better than ever and the government is taking all measures to make sure everyone is vaccinated to avoid the impending third wave. Ivermectin might have leverage over other treatment options when compared to other pharmacotherapeutic options for managing the Covid-19. Ivermectin is no new drug to the world rather it is referred to as ‘Wonder Drug’ for its versatile mechanism. This article will brief why ivermectin is considered as an option to treat the novel coronavirus and its action of mechanism.

IVERMECTIN -THE WONDER DRUG

  • For a very long time, Ivermectin (IVM)has been documented as an anti-parasitic oral drug.
  • Satoshi Omura, a Nobel Laureate discovered Ivermectin in 1979. The drug has been in use since the 1980s, adopted as human medicine which was originally used to treat a parasitic infection, Onchocerciasis.
  • Ivermectin is the dihydro derivative of Avermectin (AVM) which was initially introduced as veterinary, aquaculture, and agriculture for animal health.
  • Ivermectin was initially developed for crop management to play a role as a pesticide but later during the 1980s scientist pegged how this drug can be used to protect human beings from parasitic infection against parasites like Ascaris lumbricoides, Ancylostoma duodenale, Enterobius vermicularis, and much more.
  • Ivermectin was called the wonder drug because of its potential ability to treat River blindness (Onchocerciasis) which caused havoc in South America and parts of Africa
  • The entitlement of being called the wonder drug is shared by Aspirin and Penicillin which are the most beneficial influence on the welfare of humankind.
  • The drug has been approved for treating scabies, intestinal strongyloidiasis, and river blindness by the FDA. It is commonly available in the form of cream and lotion for treating head lice.
  • Ivermectin causes GABA gated Cl channel stimulation which results in paralysis of the infected entity by inducing hyperpolarization.
  • Over the years, several studies have pegged the possible use of Ivermectin as an anti-cancer agent in combating various cancer.

REMODEL IVERMECTIN FOR COVID-19

  • As there is no particular treatment method for COVID-19, Scientists all over the globe believe that the wonder drug Ivermectin which has been very effective for the past 30 years can be evaluated further for its efficiency to be used to treat severe COVID individuals which might decrease the admission of people to an Intense care unit in the hospital.
  • As FDA hasn’t approved Ivermectin (IVM) as an anti-viral drug, this proposal received severe criticism yet several studies were conducted to check if this wonder drug can serve as a potential ‘Magic Bullet’ against the coronavirus.
  • The exposure of Vero/ Hslam(human signalling lymphocyte -activation molecule) cells infected with SARS-CoV2 virus to 5 IVM resulted in a 93%reduction in viral RNA load in 24 hours and almost 99.8% reduction within 48 hours.
  • These in-vitro studies from Biomedicine Discovery Institute(BDI) and Peter Doherty Institute of Infection and Immunity prove how there is about a 5000-fold reduction in viral RNA load which indicates that IVM was successful in killing almost all viruses.
  • These studies serve as testimony on how repurposing IVM can aid in forming the basis of COVID-19 treatment protocol as it has served its purpose effectively in vitro test against the virus.

MECHANISM OF ACTION OF IVERMECTIN

Ivermectin
Ivermectin

It is a known fact that SARS-CoV-2 which caused the current pandemic is firmly associated with the 2002 SARS-CoV. The current SARS-CoV-2 is a single-stranded positive-sense RNA virus and IVM due to its multifactorial nature can be repurposed to fight against this 

deadly virus.

The role of IVM against the COVID-19 virus can be grouped into four categories

1. Direct action on SARS-CoV2

2. Action on host targets important for viral replication

3. Action on host targets important for inflammation

4. Action on other host targets

All these four categories consist of about 20 levels of several studies which furnish proof on how IVM can be manipulated as a drug to eradicate the current pandemic. Few interesting levels have been discussed below.

Inhibition Of Antiviral Response :

  • In vitro studies have how Ivermectin selectively inhibits the host importinβ-1 nuclear transport protein which are the crucial factors that lower the intracellular translocation process rate of SARS-CoV nucleocapsid protein (NCP) from the cytoplasm to the nucleus.
    • This Altered NCP distribution, in turn, interrupts viral procreation and durability.
    • This inhibition process done by IVM is the key step when viruses seize to magnify the infection against the host immune response.

 IVM As Ionophore

  • Ivermectin molecules reacting in pairs can form into a head-tail mode which can be considered as an ionophore given that this head-tail mode results in a complex structure.
    • IVM binds to zinc cation and forms a lipid-soluble complex that entails their transportation across several cellular membranes and exerts a direct cytotoxic effect by deregulating osmosis resulting in cell death.
    • Hence IVM as an ionophore neutralizes the virus at the premature stage of the infection before it exerts effects further.

Prohibition of Microvascular Thrombosis:

  • CD147-mediated catch and clump mechanism which terminates as silent hypoxia can be prevented by the action of Ivermectin according to studies.
  • IVM regulates the microvascular abnormalities by diminishing the CD-147 pathway whose receptors on RBC s are responsible for SARS-CoV-2 adhesion. 
  • Hence depending on the concentration of IVM, it can be used to prevent adhesion of COVID-19 virus and also microvascular thrombosis.

Blockage Of Entry And Sequestration:

  • IVM blocks the entry of the virus into the host cell by adhering to the spike receptor-binding domain which is attached to the angiotensin-converting enzyme 2 (ACE2) receptor.
  • IVM also has been located in the pulmonary tissue and is sequestered in the same location with an extensive accommodation period.

CONCLUSION :

In these desperate times of COVID-19 pandemic where there is the detection of various new mutant strains, Ivermectin which entails a broad spectrum of activities with its anti-inflammatory, anticancer, antimicrobial properties is worth the attention and need to be clinically investigated for its efficacy and potential as an anti-viral agent in both in vivo and in vitro condition as it might be a hope till there is definite drug or vaccine against COVID-19 for humankind.

RESOURCES:

Gupta, D., Sahoo, A. K., & Singh, A. (2020). Ivermectin: a potential candidate for the treatment of Covid 19. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases24(4), 369–371. https://doi.org/10.1016/j.bjid.2020.06.002

Wehbe, Zena & Wehbe, Maya & Iratni, Rabah & Pintus, Gianfranco & Zaraket, Hassan & Yassine, Hadi & Eid, Ali. (2021). Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities. Frontiers in Immunology. 12. 663586. 10.3389/fimmu.2021.663586.

Zaidi, A.K., Dehgani-Mobaraki, P. The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article. J Antibiot (2021). https://doi.org/10.1038/s41429-021-00430-5

Liu, J., Zhang, K., Cheng, L., Zhu, H., & Xu, T. (2020). Progress in Understanding the Molecular Mechanisms Underlying the Antitumour Effects of Ivermectin. Drug design, development and therapy14, 285–296. https://doi.org/10.2147/DDDT.S237393

RASTOGI, H. and AGGARWAL, K., 2021. Ivermectin – A Potent Weapon in the Anti-COVID-19 Armamentarium. Indian Journal of Clinical Practice, 31(5).

https://clinicaltrials.gov/ct2/show/NCT04602507

https://www.fda.gov/consumers/consumer-updates/why-you-should-not-use-ivermectin-treat-or-prevent-covid-19