Repurposing existing medicines focused on known drug targets is likely to offer a hope of more rapidly tackling COVID-19 than developing and manufacturing a vaccine, argues an international team of scientists in the British journal Pharmacology Today.
Since the emergence of the coronavirus in late 2019, more than 3.5 million people are known to have been infected, leading to over 240,000 deaths worldwide from COVID-19 as of May 1. The race is on to find new drugs to treat COVID-19 patients, and to develop a vaccine to prevent infection in the first place.
A team of researchers representing the International Union of Basic and Clinical Pharmacology said there will be no "magic bullet" to treat the disease and contends that a multi-pronged approach is needed to find new drugs. They caution that an effective and scalable vaccine is likely to take more than a year before it can be used to tackle the global pandemic.
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WHAT'S THE IMPACT?
When a virus enters a person's body, unless they have already developed immunity from previous infection or vaccination, it will break into their cells, hijacking those cells' machinery and using it to replicate and spread throughout the body. Often, the symptoms that are visible are a result of the immune system fighting back in an attempt to clear the infection. In severe cases, this immune response can become overactive, potentially leading to a so-called cytokine storm, causing collateral damage to organs along the way.
The review looks at potential therapeutic drug targets -- the chinks in the virus's own armor or weak spots in the body's defenses. Two key targets appear to be proteins on the surface of a person's cells, to which SARS-CoV-2 binds, allowing it entry – ACE2 and TMPRSS2. TMPRSS2 appears to be very common on cells, whereas ACE2 is usually present at low levels that increase depending on sex, age, and smoking history.
Since those two proteins play a role in coronavirus infection, existing drugs can be repurposed – ones that already have regulatory approval or are in the late stages of clinical trials.
One promising candidate is remdesivir, a drug originally developed for Ebola. Although clinical trials found it to be insufficiently effective at treating Ebola, clinical trials in the U.S. have suggested the drug may be beneficial for treating patients hospitalized with COVID-19, and the FDA has now approved it for emergency use. There have also been promising findings from studies of monoclonal antibodies, but this type of drug is expensive to produce and therefore less likely to be scalable.
The team said it would be best to move quickly to identify existing drugs that are effective in clinical trials – so patients can start being treated as rapidly as possible, but also because cases are likely to fall during the summer. That means there will be fewer people who can be recruited to clinical trials ahead of an anticipated second wave of the disease in autumn. The authors estimate there are currently more than 300 clinical trials taking place worldwide, though many of these investigational drugs are unlikely to be effective for widespread use, because either it is not clear which part of the disease pathway they are targeting, or they cause unpleasant side effects.
They also advise patience for the promise of developing an effective vaccine against the virus. Even after a new vaccine candidate has been shown to offer immunity against the coronavirus in humans, it needs to be tested in larger numbers of people to ensure it is safe to use.
THE LARGER TREND
The rapidly escalating demand for medications due to COVID-19 is placing increased pressure on hospitals and health systems to appropriately manage drug inventory to support patient care. Essential medications used to alleviate breathing difficulties, relieve pain and sedate coronavirus patients are in short supply.
Meanwhile, Vizient found in late March that there has been a 6,842% increase in chloroquine tablets ordered, with fill rates dropping to as low as 1.4%, and a 2,196% increase in hydroxychloroquine tablets ordered, with fill rates dropping to as low as 12.1%, since March 16, when the World Health Organization declared COVID-19 to be a pandemic.