Smooth or Risky Revisit of an Old Malaria Drug for COVID-19?

Abstract

Hydroxychloroquine (HCQ) is an old medication for malaria. In addition to handling this parasitic disease, HCQ is also used to treat a number of autoimmune disorders including rheumatoid arthritis and systemic lupus erythematosus when other medications are not effective. Recently a new viral infection (COVID-19) is rocking the entire world so much that it has already taken more than 200,000 lives throughout the world within the last two months and the World Health Organization was forced to declare it as a pandemic on March 11, 2020. Interestingly, some reports indicate that this wonder drug may be also beneficial for COVID-19 and accordingly, many clinical trials have begun. Here, we discuss different modes of action (anti-inflammatory, antioxidant, inhibition of endosomal acidification, suppression of angiotensin-converting enzyme 2 or ACE2 glycosylation, etc.) of HCQ that might be responsible for its possible anti-COVID-19 effect. On the other hand, this review also makes an honest attempt to delineate mechanisms (increase in vasoconstriction, inhibition of autophagy, depletion of T cells, etc.) indicating how it may aggravate certain conditions and why caution should be taken before granting widespread repurposing of HCQ for COVID-19.

Mutagenic, Genotoxic and Immunomodulatory effects of Hydroxychloroquine and Chloroquine: a review to evaluate its potential to use as a prophylactic drug against COVID-19

“…HCQ can potentially interfere with intracellular calcium signaling and prevent dephosphorylation and activation of the transcription factor NFAT. This is one of the mechanisms by which HCQ interfere in T-cell activation and CD 154 transcription also been shown to reduce this glycosylation step [68]. These studies have together motivated healthcare workers to use these drugs as a prophylactic, postexposure prophylactic, and as a curative drug.…”

Hydroxychloroquine and Covid-19: A Cellular and Molecular Biology Based Update

“…Hydroxychloroquine may suppress immune function by interfering with the processing and presentation of antigens, and the production of cytokines. Acidic vesicles, such as endosomes/lysosomes, which are essential for the membrane fusion, act as major locations of action of chloroquine and hydroxychloroquine [2,3,40]. Chloroquine accumulates in lysosomes (lysosomotropism), and by increasing their pH, interferes with the glycosylation of cellular receptor of SARS-CoV-2 and thereby inhibits the infection of virus [14,40].…”

“…Reduced activation of CD4 ? T cells leads to decreased production of proinflammatory markers and cytokines [14,40]. It has been suggested that autophagy is involved in autoantigen presentation mediated by MHC class II molecules, and activation of T-helper cells [43].…”

“…Hydroxychloroquine has attracted attention over the past few decades as a potential antiviral agent, and currently as a possible treatment for Covid-19 [40,61,62]. However, whether hydroxychloroquine works in vivo against Covid-19 remains to be seen conclusively.…”

“…Another issue with hydroxychloroquine is adverse outcomes in certain patients with comorbid conditions who are on other medications [40,61,62]. It has been reported that hydroxychloroquine can also interfere with drugs that affect the QT interval [57].…”