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Hydroxychloroquine, the anti-malaria drug controversially touted as a remedy for COVID regardless of a scarcity of strong proof, is creating renewed curiosity as a possible therapy for omicron.
The dialogue has been sparked by a brand new examine from the College of Glasgow, which is but to be revealed in a scientific journal, that appears at how antibodies from vaccines block omicron from coming into cells. The researchers conclude, as many others have, that antibodies (the proteins that neutralise the virus) towards earlier variants or induced by vaccines are much less efficient towards omicron. What’s fascinating, although, is that the examine finds that omicron might have modified the best way it enters cells.
SARS-CoV-2, the virus that causes COVID, is coated in a lipid bilayer (a skinny membrane fabricated from two layers) identical to our cells. When the virus enters our cells, the bilayers fuse like oil droplets on the floor of water, termed “membrane fusion”.
Membrane fusion happens after the SARS-CoV-2 spike protein has hooked up to the ACE2 receptor on the cell floor, however can occur in two completely different locations (see diagram beneath). Membrane fusion can happen on the cell’s floor, or it may can happen after the SARS-CoV-2 virus has been engulfed in an endosome.
The 2 methods coronavirus enters your cells
PLOS Pathogens, CC BY
An endosome happens when the cell’s membrane folds again in on itself, making a bubble of outdoor materials contained in the cell as a way to take up vitamins. Usually the cell will then kind by means of the fabric and preserve helpful vitamins whereas discarding others. Nonetheless, many viruses exploit endosomes as a technique to enter cells.
Because of this SARS-CoV-2 has two methods to enter cells: from the floor or by way of an endosome. The College of Glasgow examine exhibits that omicron has picked up mutations that enhance its capability to enter our cells by way of endosomes – and that is the place hydroxychloroquine comes into play.
Hydroxychloroquine (HCQ) is a drug that accumulates in endosomes and reduces their acidity, which disrupts their perform. Making endosomes much less acidic reduces membrane fusion, thereby lowering SARS-CoV-2’s capability to enter cells. So HCQ might act as an antiviral.
That is probably how HCQ acts as an anti-malarial and anti inflammatory drug (though some researchers dispute this). It’s necessary to notice that the brand new examine doesn’t take a look at HCQ’s impact on omicron.
Hydroxychloroquine has had a troublesome pandemic
HCQ has change into infamous in the course of the pandemic. The primary examine claiming HCQ is efficient towards COVID was criticised by science fraud professional Elisabeth Bik, who questioned the ethics, timelines for the trials, a scarcity of randomisation for sufferers and lacking information.
Didier Raoult, the lead creator of the work, then filed a prison criticism towards Bik for ethical harassment, blackmail and extortion. Throughout this, the French president, Emmanuel Macron, promoted HCQ – I assume in help of a fellow Frenchman, whereas use of the drug was additionally supported by Donald Trump, for causes solely clear to Donald Trump.
Extra bizarrely, a examine revealed within the Lancet urged that HCQ therapy truly elevated fatalities, although this latter examine has been accused of information fraud as effectively. All through all of this, different researchers have failed to search out any constructive advantages for HCQ, or robust indications for side-effects. HCQ has to date been an instance of science at its worst.
However will hydroxychloroquine be efficient towards omicron? I battle to see the advantages of treating omicron infections with HCQ. Within the College of Glasgow examine, the researchers present that omicron enters cells by way of endosomes extra so than different variants, however they don’t present that omicron is restricted to utilizing endosomes. It may possibly nonetheless enter from the cell floor. Utilizing HCQ to cease omicron coming into by way of endosomes would due to this fact solely marginally restrict the virus from coming into cells.
To indicate that HCQ is efficient towards omicron, scientists have to infect cells with omicron within the presence and absence of HCQ and exhibits a big discount in infectivity. If this exhibits that HCQ is efficient towards omicron, it might be smart to check HCQ in a medical trial.
Nonetheless, not like in March 2020 when HCQ was first urged as a therapy, now we have loads of medicine to deal with COVID together with antivirals, resembling molnupiravir and remdesivir, anti-inflammatories, resembling dexamethasone, and antibody therapies.
Ben Krishna doesn’t work for, seek the advice of, personal shares in or obtain funding from any firm or organisation that will profit from this text, and has disclosed no related affiliations past their educational appointment.