Ivermectin: a multifaceted drug of Nobel prize-honoured distinction with indicated efficacy against a new global scourge, COVID-19
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A.D.Santin1D.E.Scheim2P.A.McCullough3M.Yagisawa4T.J.Borody5
1)Department of Obstetrics & Gynecology, Yale University School of Medicine, New Haven, CT, USA
2)US Public Health Service, Inactive Reserve, Blacksburg, VA, USA
3)Texas A & M College of Medicine, Dallas, TX, USA
4)ÅŒmura Satoshi Memorial Institute, Infection Control Research Center, Kitasato University, Tokyo, Japan
5)Centre for Digestive Diseases, New South Wales, Australia
Available online 3 August 2021.
Abstract
In 2015, the Nobel Committee for Physiology or Medicine, in its only award for treatments of infectious diseases since six decades prior, honoured the discovery of ivermectin (IVM), a multifaceted drug deployed against some of the world’s most devastating tropical diseases. Since March 2020, when IVM was first used against a new global scourge, COVID-19, more than 20 randomized clinical trials (RCTs) have tracked such inpatient and outpatient treatments. Six of seven meta-analyses of IVM treatment RCTs reporting in 2021 found notable reductions in COVID-19 fatalities, with a mean 31% relative risk of mortality vs. controls. During mass IVM treatments in Peru, excess deaths fell by a mean of 74% over 30 days in its ten states with the most extensive treatments. Reductions in deaths correlated with the extent of IVM distributions in all 25 states with p < 0.002. Sharp reductions in morbidity using IVM were also observed in two animal models, of SARS-CoV-2 and a related betacoronavirus. The indicated biological mechanism of IVM, competitive binding with SARS-CoV-2 spike protein, is likely non-epitope specific, possibly yielding full efficacy against emerging viral mutant strains.
Introduction
The 2015 Nobel prize for the discovery of ivermectin (IVM) and an antimalarial treatment was the Nobel committee’s first award for treatment agents for infectious diseases since the one in 1952 for streptomycin [1]. A macrocyclic lactone of multifaceted potency [2,3], IVM as deployed worldwide since 1987 has made major inroads against two devastating tropical diseases, onchocerciasis and lymphatic filariasis [4]. During the year since IVM treatment was first applied to COVID-19, another global scourge [5], results from more than 20 randomized clinical trials (RCTs) of IVM treatment of COVID-19 have been reported [2,6,7], with inpatient and outpatient treatments of COVID-19 conducted in 25 countries [2]. A likely biological mechanism has been indicated to be competitive binding with SARS-CoV-2 spike protein sites, as reviewed [8,9].
Recently, Dr Satoshi Omura, the Nobel co-laureate for the discovery of IVM, and colleagues conducted a comprehensive review of IVM clinical activity against COVID-19, concluding that the preponderance of the evidence demonstrated major reductions in mortality and morbidity [2]. Our review of that evidence, updated with consideration of several new studies, supports the same conclusion.
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http://www.sciencedirect.com/science/article/pii/S2052297521000883