Does a new study really show that hydroxychloroquine may be effective against omicron?

Hydroxychloroquine, the antimalarial drug controversially promoted as a treatment for COVID despite the lack of strong evidence, is creating renewed interest As a potential treatment for Omicron.

The discussion was sparked by a new study from the University of Glasgow, which has not yet been published in a scientific journal, that looks at how antibodies from vaccines prevent the omicron from entering cells. The researchers concluded, as have others, that antibodies (proteins that neutralize the virus) against earlier variants or stimulated by vaccines are less effective against omicron. What’s interesting, however, is that the study found that the omicron may have changed the way it enters cells.

SARS-CoV-2, the virus that causes COVID, is covered in a lipid bilayer (a thin membrane made of two layers) just like our cells. When the virus enters our cells, the bilayers fuse like oil droplets on the surface of the water, this is called “membrane fusion”.

Membrane fusion occurs after the SARS-CoV-2 protein binds to the ACE2 receptor on the cell surface, but can occur in two different locations (see graph below). Membrane fusion can occur at the cell surface, or it can occur after SARS-CoV-2 virus has been engulfed in an endosome.

Two ways the coronavirus enters your cells

How does the coronavirus fuse with a cell?
SARS-CoV-2 fusion can be activated by one or both pathways. Omicron may prefer the first method, via endosomes. Pathogens Plus, CC BY

Endosomes occur when the cell membrane folds back in on itself, creating a bubble of external substance inside the cell for the absorption of nutrients. Normally the cell then sorts out the material and retains the beneficial nutrients while getting rid of others. However, many viruses exploit endosomes as a means of entering cells.

This means that SARS-CoV-2 has two ways of entering cells: from the surface or through the endosome. The University of Glasgow study shows that omicron has picked up mutations that improve its ability to enter our cells via endosomes – that’s where hydroxychloroquine comes in.

Hydroxychloroquine (HCQ) is a drug that accumulates in endosomes and reduces their acidity, disrupting their function. Making endosomes less acidic reduces membrane fusion, which reduces the ability of SARS-CoV-2 to enter cells. So HCQ can act as an antiviral.

This is probably how HCQ works as an anti-malarial and anti-inflammatory drug (although some researchers are skeptical). It is important to note that the new study does not test the effect of HCQ on Omicron.

Hydroxychloroquine was a tough epidemic

HCQ became infamous during the pandemic. The first study that claimed HCQ is effective against COVID was criticized by scientific fraud expert Elizabeth Beck, who questioned the ethics, trial schedules, lack of randomization of patients, and missing data.

Didier Raoult, the lead author of the work, filed a criminal complaint against Beck for moral harassment, extortion and extortion. During this, French President Emmanuel Macron promoted HCQ – I suppose in support of a French citizen, while the use of the drug was also subsidized by Donald Trump, for reasons that are only apparent to Donald Trump.

Even more surprisingly, a study published in The Lancet suggested that HCQ treatment did indeed increase deaths, although this latest study has also been accused of falsifying the data. Throughout all of this, other researchers have failed to find any positive benefits of HCQ, or strong indicators of side effects. HCQ has so far been the epitome of science at its worst.

But will hydroxychloroquine be effective against Omicron? I find it hard to see the benefits of treating an omicron infection with HCQ. In a study by the University of Glasgow, researchers show that omicrons enter cells via endosomes more than other variants, but they don’t show that omicrons are restricted to the use of endosomes. It can still enter from the cell surface. Thus the use of HCQ to block the entry of the omicron via endosomes would only marginally limit virus entry into cells.

To demonstrate that HCQ is effective against the omicron, scientists need to infect cells with the omicron in the presence and absence of HCQ and show a significant reduction in infection. If this shows that HCQ is effective against omicron, it would be reasonable to test HCQ in a clinical trial.

However, unlike in March 2020 when HCQ was first suggested as a treatment, we have a lot of drugs to treat COVID including antivirals, such as molnupiravir and remdesivir, and anti-inflammatories, such as dexamethasone, and antibody therapies.

Ben Krishna, Postdoctoral Researcher, Immunology and Virology, Cambridge University

This article has been republished from The Conversation under a Creative Commons license. Read the original article.

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