Infectious Diseases

Hydroxychloroquine: a Less Toxic Coronavirus Treatment?

Posted on 24 March 2020

The drug chloroquine phosphate has attracted significant media attention recently, and there is debate over whether its promise as a treatment for COVID-19 has been overstated. In vitro experiments suggest that Chloroquine is effective against SARS-Cov-2. Its benefit in a clinical environment is less well established, and multiple clinical trials are underway to assess its effectiveness.

One of the reasons chloroquine seems particularly promising is that it is not a new drug: chloroquine has long been used as a malaria treatment and prevention. This means that compared to more experimental drugs (such as remdesivir), large-scale production of choroquine in a short timescale is much more feasible.

Unfortunately, chloroquine has a major drawback in the form of its potentially dangerous side effects, especially in those with heart conditions – one of the groups most at risk of dying due to COVID-19. Furthermore, the dose required to treat COVID-19 in Chinese studies was quite large: roughly 2.5 times the dose for malaria treatment.

Now, research published in Cell Discovery suggests that hydroxychloroquine, a derivative of chloroquine, may provide a less toxic alternative. Hydroxychloroquine and chloroquine prevented the virus from escaping the endosome (the organelle in which the virus is enclosed when it enters the cell):

Red: virions Green: endosomes Blue: nucleus
Viral particles remain within endosomes when treated

However, hydroxychoroquine is significantly less toxic than its couterpart, meaning it could achieve the same benefits as chloroquine with a safer dose. If it proves effective in human trials, hydroxychloroquine may therefore be a preferable alternative.

It was reported that safe dosage (6–6.5 mg/kg per day) of HCQ sulfate could generate serum levels of 1.4–1.5 μM in humans. Therefore, with a safe dosage, HCQ concentration in the above tissues is likely to be achieved to inhibit SARS-CoV-2 infection

Liu, J., Cao, R., Xu, M., Wang, X., Zhang, H., & Hu, H. et al. (2020). Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discovery6(1). doi: 10.1038/s41421-020-0156-0

References

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro: https://doi.org/10.1038/s41422-020-0282-0

Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro: https://doi.org/10.1038/s41421-020-0156-0

Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate: https://doi.org/10.1016/0002-9343(83)91265-2

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