WHY ANYONE would prescribe a substance such as Chloroquine Phosphate for the treatment of Covid-19 is a mystery. For starters the anti-malaria drug is an amebicide, ‘an agent used in the treatment of amoebozoa infections, called amoebiasis’ and is not an anti-viral as such.
It has a low LD50, the lethal dose at which rats and patients die (low is more toxic). It has been touted by both the Trump administration and the World Health Organisation as a treatment for the disease but has been lambasted by critics. Chloroquine: Trump’s misleading claims spark hoarding and overdoses reads one headline.
On the March 19, South Africa adopted Chloroquine Phosphate in its guidelines for the clinical management of Covid-19, published by the Department of Health and the National Institute for Communicable Diseases. A local pharmaceutical company has received permission from the medical regulator to import half a million chloroquine phosphate tablets.
New research published on Wednesday however, ‘suggested that “off label” re-purposing of drugs such as hydroxychloroquine could lead to “drug-induced sudden cardiac death”. The paper by the Mayo Clinic, a nonprofit medical organisation, found that ‘chloroquine and Kaletra, a HIV drug also being used against coronavirus, can cause the heart muscle to take longer than normal to recharge between beats.’
Most RNA viruses develop solely in cytoplasm (a thick solution that fills each cell and is enclosed by the cell membrane.) Unlike plasmodium malaria (amoebozoa ) viral populations do not grow through cell division, because they are acellular.
Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm.
‘To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis.’
There are over 100 known drug compounds capable of disrupting the viral replication of Sars-CoV-2, the coronovirus responsible for COVID-19. These substances have been located via an unprecedented bioinformatics search by two groups of scientists working round-the-clock on the equivalent of the Manhattan Project.
Their findings were published less than three weeks apart and must be considered required reading by anyone working in the field of coronovirus medicine. Unfortunately due to politics surrounding branded drugs and the Trump administration, and the machinations of the World Health Organisation, and our own government, these findings are being ignored.
Local use of the drug appears to pre-empt a WHO trial already underway in Norway and Spain.
Although Chloroquine Phosphate, ‘the phosphate salt of chloroquine, a quinoline a compound with antimalarial and anti-inflammatory properties’ appears on one of the lists provided by the researchers, the substance is not recommended by doctors as anything more than a last resort.
The chief executive of Novartis cautioned on Friday that it is “too soon” to be sure whether the anti-malaria drugs could be a definitive treatment for the coronavirus.
“Researchers have tried this drug on virus after virus, and it never works out in humans. The dose needed is just too high,” says Susanne Herold, an expert on pulmonary infections at the University of Giessen,
The latest list of potential coronovirus drugs discovered via an unprecedented bioinformatics search, include many compounds already approved for administering by doctors, some are already in preclinical trials. Among them is a 1971 antiviral drug, Ribavirin capable of disrupting the RNA synthesis of the coronovirus itself, the bug responsible for the biggest health crisis event of the 21st Century.
The drug is described in a paper aptly entitled ‘Broad-spectrum coronavirus antiviral drug discovery‘. It escaped media attention, perhaps due to its patent rights lapsing, while Lopinavir–Ritonavir, a relatively new HIV drug has received a lot of press, alongside Favivlavr a drug from China approved by the National Medical Products Administration of China . Clinical trials of a promising COVID-19 antiviral, Remdesivir, which gets incorporated into viral RNA and prevents it being synthesised, halting viral replication, are currently underway.
Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers.
A team lead by Nevan Krogan of the Gladstone Institute, working around the clock have identified more than 300 human proteins that interact with SARS-CoV-2 during infection.
Since the Trump announcement there has been attempts to classify coronovirus medicine research and restrict any adverse criticism of Chloroquine, with EPA announcing broad restrictions.
Efforts to raise awareness amongst local organisers of a Peninsula community coronovirus response team were instead met with ridicule, and the writer threatened with prosecution. The lack of debate amongst local authorities is reminiscent of the HIV-denial era, since anyone publishing coronovirus information ‘not authorised by the DOH ‘ may run foul of recently gazetted regulations governing the spread of information.
It is safe to say when this epidemic broke, we were dealing with denialists who refused to believe there was an epidemic. Overnight, these same folk have turned into gatekeepers of what can and cannot be said. Now even government officials are denying there are any antiviral treatments capable of bringing down the epidemic to manageable proportions and urging us all to use Chloroquine the most widely used drug against malaria.
The safety issues here are also reminiscent of the thalidomide disaster, one of the darkest episodes in pharmaceutical research history
Although the mechanism of action is not fully understood, chloroquine has been shown to inhibit the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite.
Chloroquine may also interfere with the biosynthesis of nucleic acids. However the coronovirus is not a microbial parasite and more research on the use of the substance in symptomatic treatment of a condition associated with an RNA virus would be required.
The most important lesson of the 1918 influenza pandemic: Tell the damn truth