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THE SEARCH FOR SAFE AND EFFECTIVE TREATMENT OF COVID-19- A LOOK AT IVERMECTIN

I saw something very interesting recently in relation to the treatment of COVID-19 (SAR-CoV-2). It is Ivermectin, a drug approved by the Food & Drug Administration (FDA) for the treatment of parasitic infections. Ivermectin is a semisynthetic derivative of avermectin B1 and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b

This is an antiparasitic agent, developed by Merck & Co., and frequently used in veterinary medicine, due to its broad spectrum of activity, high efficacy and wide margin of safety.The first formulation destined to humans was launched in 1987, when Merck Laboratories had enough data to register ivermectin for use against onchocerciasis. The company announced that the drug would be provided at no cost to treat onchocerciasis, anywhere in the world, for as long as it was needed. Yes, I saw this early in my practice and many colleagues were highly appreciative of Merck & Co for the intervention.

To control onchocerciasis, the Onchocerciasis Control Programme in West Africa was launched in 1974. The main goal of this program was to interrupt the parasite transmission cycle. Since 1987, the use of ivermectin in combination with aerial larviciding has had a remarkable impact on the transmission of the disease and greatly reduced the effect on humans. This led to the development, in 1992, of the Onchocerciasis Elimination Programme in the Americas, launched in 6 countries and, in 1995, of the African Programme for Onchocerciasis Control, both based mainly on distribution and treatment with ivermectin. In 1998, the Global Programme to Eliminate Lymphatic Filariasis, based on the regular mass administration of albendazole with either ivermectin or diethylcarbamazine, was initiated, confirming the safety and efficacy of the drug combinations.

There is an intense search by the scientific community for an effective and safe treatment of COVID-19. As a result, old molecules with proven antiviral activity are being tried. In a News Release in EurekAlert on 3rd April 2020 by Monash University, a collaborative study led by Monash University’s Biomedicine Discovery Institute (BDI) in Melbourne, Australia, with the Peter Doherty Institute of Infection and Immunity (Doherty Institute), has shown that an anti-parasitic drug, Ivermectin, already available around the world kills COVID-19 within 48 hours.The Monash Biomedicine Discovery Institute’s Dr Kylie Wagstaff, a member of the study, said the scientists showed that the drug, Ivermectin, stopped the SARS-CoV-2 virus growing in cell culture within 48 hours.Even a single dose could essentially remove all viral RNA by 48 hours and that even at 24 hours there was a really significant reduction in the viral RNA.

Ivermectin is an FDA-approved anti-parasitic drug that has also been shown to be effective in vitro against a broad range of viruses including HIV, Dengue, Influenza and Zika virus.The caution here is that the tests conducted in the study were in vitro and that trials needed to be carried out in people.There is the need to determine dosing regimen, for example, in humans. The  author adds that in a time of a global pandemic and with no approved if there is  a compound already  available around the world, then that it might help people sooner. He adds that realistically it is going to be a while before a vaccine is broadly available.

The mechanism of action of Ivermectin is likely, based on its action in other viruses-, that it works to stop the virus ‘dampening down’ the host cells’ ability to clear it. Dr Leon Caly of the Royal Melbourne Hospital and a Senior Medical Scientist at the Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute where the experiments with live coronavirus were conducted, is the study’s first author.He is a virologist who was part of the team to first isolate and share SARS-COV2 outside of China in January 2020. He is  excited about the prospect of Ivermectin being used as a potential drug against COVID-19. It seems the scientific community maybe onto something significant with Ivermectin, becauseDr Wagstaff herself made a previous breakthrough finding on Ivermectin in 2012 when she identified the drug and its antiviral activity with Monash Biomedicine Discovery Institute’s Professor David Jans, also an author on this paper on its effect against COVID-19. Professor Jans and his team have been researching Ivermectin for more than 10 years with different viruses.The team started investigating whether it worked on the SARS-CoV-2 virus as soon as the pandemic was known to have started.

The abstract to this study captures the mood of the scientific community on the search for treatment for COVID-19. Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring and containment. The preliminary report is that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 hours post infection with SARS-CoV-2 able to effectabout 5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.

Ivermectin is an FDA-approved broad spectrum anti-parasitic agent HYPERLINK “https://www.sciencedirect.com/science/article/pii/S0166354220302011” \l “bib1” 1 that in recent years, along with other groups, have shown to have anti-viral activity against a broad range of viruses in vitro. Importantly, Ivermectin, has been demonstrated to limit infection by RNA viruses such as DENV 1-4, West Nile Virus, Venezuelan equine encephalitis virus (VEEV) and influenza. Ivermectin has similarly been shown to be effective against the DNA virus pseudorabies virus (PRV) both in vitro and in vivo. Finally, ivermectin was the focus of a phase III clinical trial in Thailand in 2014-2017, against DENV infection, in which a single daily oral dose was observed to be safe and resulted in a significant reduction in serum levels of viral NS1 protein. 

The causative agent of the current COVID-19 pandemic, SARS-CoV-2, is a single stranded positive sense RNA virus that is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV). Ultimately, development of an effective anti-viral for SARS-CoV-2, if given to patients early in infection, could help to limit the viral load, prevent severe disease progression and limit person-person transmission. Benchmarking testing of ivermectin against other potential antivirals for SARS-CoV-2 with alternative mechanisms of action would thus be important as soon as practicable.

The use of Ivermectin to combat COVID-19 would depend on the results of further pre-clinical testing and ultimately clinical trials. I would not be surprised if Merck & Co offers to the global community for free again in light of the COVID-19 pandemic.

DR. EDWARD O. AMPORFUL

CHIEF PHARMACIST

COCOA CLINIC

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