By Dr. Shari Jainuddin ND
Last week, Donald Trump mentioned chloroquine and hydroxychloroquine as possible effective agents in the fight against the current pandemic. Chloroquine has an established history for treating some strains of malaria by interfering with the erythrocytic (blood) stage of its parasitic replication cycle. Hydroxychloroquine, a less toxic sulfate form of chloroquine, is also used for its immune modulating properties in treating lupus and rheumatoid arthritis. It may be easier to draw a line between hydroxychloroquine’s immune modulating effects and its possible treatment of CoVid-19 in my recent article discussing immune response and symptom severity. But how are these anti-parasitic agents possibly useful against a viral infection such as SARS-CoV-2? Here, I investigate that further.
It turns out this isn’t the first time that chloroquine has been looked at in the treatment of acute viral diseases in humans. Its antiviral potential has been noted in research dating back several decades including inhibition of the growth of SARS, another coronavirus. Successful in vitro (cell culture) studies have unfortunately not carried over to in vivo (animal) models. In one viral study specifically, chloroquine’s preliminary antiviral effects in vitro actually enhanced viral replication and fever and delayed cellular immune response once it researched in an animal trial.(1) It appears that many of the promising in vitro results have yet to show efficacy in animal models, a common hurdle in research.
How do they work as an antivirals? Chemically, chloroquine and hydroxychloroquine are both weak bases and have been shown to change the pH inside the cell. It is suggested that this intracellular change in pH, from acidic to more basic, inhibits cell membrane fusion of the virus directly (it can’t attach to cells) as well as interfering with components necessary for intracellular transport of SARS-CoV-2, a step needed for the viral genome to be released.(1) This change in pH is also key to its efficacy in treatment of malaria.(2) Such evidence does warrant further research.
So why is the spotlight on these agents in the fight against the coronavirus? Outside of the research just mentioned, it is likely due to China’s recent claim that in 100 patients, chloroquine phosphate was “superior to the control treatment” in fighting against the ill effects of the coronavirus. However, China has NOT released any data or evidence supporting this claim.(3) The world is still waiting.
Such claims need to be substantiated. On Monday, March 23rd, the WHO Director discussed the necessity to not only have strong defensive measures (i.e. social distancing and staying at home) but also the need for an offensive approach (therapeutic agents) in order to win the fight against this disease. General Tedros reiterated that therapeutics need to be researched, emphasizing that, “There is currently no treatment that has proven to be effective against Covid-19. Small observational and non-randomized studies will not give us the answers we need. Using untested medicine without the right evidence could raise false hope and even do more harm than good and cause a shortage of essential medicines that are needed to treat other diseases.” He also highlighted the recent launch of the Solidarity Trial, a large-scale group of many countries that have joined together in the common goal of finding an effective treatment based on robust, high-quality evidence.(4,5) Tedros rallied, “the more countries that sign up the faster we will get results on which drugs work and the more lives we will be able to save.” So far, it appears there are eight countries, not including the United States, that have joined the Solidarity Trial. Notably, chloroquine is on the list of drugs to be researched.(6)
- Liu, J., Cao, R., Xu, M. et al., 2020. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discovery, 6(1).
- Touret, F., De Lamballerie, X., 2020. Of Chloroquine and COVID-19. Antiviral Research, 177, p. 104762.
- Hydroxychloroquine: Drug Information. UpToDate. Retrieved March 23, 2020, from https://www.uptodate.com/contents/hydroxychloroquine-drug-information
- Coronavirus: WHO Head Says Nations Must Attack As ‘Pandemic Is Accelerating’ : Coronavirus Live Updates : NPR https://www.npr.org/sections/coronavirus-live-updates/2020/03/23/820290984/coronavirus-who-head-says-nations-must-attack-as-pandemic-is-accelerating
- UN News https://news.un.org/en/story/2020/03/1059722
- World Health Organization: Thailand joins the WHO “Solidarity Trial”: global testing of effective treatments of COVID-19 across 8 countries – an aggressive effort to save lives from the pandemic https://www.who.int/thailand/news/detail/20-03-2020-thailand-joins-the-who-solidarity-trial-global-testing-of-effective-treatments-of-covid-19-across-8-countries-an-aggressive-effort-to-save-lives-from-the-pandemic