Researchers from the Chinese Academy of Sciences uncovered an antibiotic approved for the treatment of pneumonia actually binds to the same receptors that SARS-CoV-2 itself attaches to in human cells. Called ceftazidime, the Chinese researchers suggest this drug could inhibit or even prevent COVID-19. Published recently in the preprint server bioRxiv, this work is not peer reviewed and hence cannot be considered authoritative. Nonetheless, the intriguing findings were derived from an intensive screening of over 3,500 FDA-approved drug targets as well as small molecules.
TrialSite offers a brief breakdown of this work out of China.
Where is the study published?
In the non-peer reviewed preprint server bioRxiv.
Where are the researchers from?
Chinese Academy of Sciences and other institutions, such as Shanghai Institute of Biochemistry and Cell Biology.
What is the underlying premise in this research for how COVID-19 infects humans?
Due to the “spike” protein, which apparently evolved in this particular pathogen to be able to attach to the angiotensin-converting enzyme 2 (ACE2) located on the host cells. More specifically, there is a part of this protein thatin sections or areas known as receptor binding domains (RBDs) actually attach to the angiotensin-converting enzyme 2 (ACE2) found on host cells. Hence, upon binding of RBDs to the ACE2, SARS-CoV-2 actually melds with the host cell membrane and the infection occurs.
Why is targeting the repurposing of drugs important?
Due to the length of time and cost of developing new drugs, a repurposing strategy should be considered. Hence why these researchers targeted for screening existing approved drugs and small molecules.
How many targets did the researchers screen? Where did they find them?
3,581 total small molecules, found through the FDA Approved Drug Library, Spectrum Collection and Targetmol Natural Compound Library.
How did the researchers perform the screens?
AlphaScreen, a high throughput screening approach.
How many targets evidenced promise?
First, they narrowed the search down to 75 compounds after just the first wave of screening. These compounds exhibited 45% or more inhibition. The team then refined the screening down to 10 compounds, which led to the following compound: bleomycin sulfate, levodopa, norepinephrine, trientine, hydrochloride, ceftazidime, chiniofon, hematein, theaflavin, bleomycin and myricetin.
What compounds exhibited the most promise?
Ceftazidime as it was recorded has the greatest inhibition rate at about 81%.
What is Ceftazidime?
Sold under the trade name Fortaz, and others, this antibiotic is used for treating a number of bacterial infections. More specifically, it’s commonly prescribed for joint infections, meningitis, pneumonia, sepsis and others. It is typically administered via injection into the vein.
The drug was patented in 1978 and became commercialized by 1984. On the World Health Organization’s List of Essential Medicines, its available as a genetic medication.
See an FDA label for Fortaz, which lists side effects as well.
What else did the Chinese Academy of Sciences researchers uncover?
The team discovered that ceftazidime actually binds to the coronavirus spike protein’s RBD; however, it doesn’t bind with the ACE2 extracellular domain. The team discovered that ceftazidime stopped binding of SARS-CoV-2 RBDs to the human pulmonary alveolar epithelial cells or lung cell, one that additionally expresses ACE2.
The researchers experiments found that Ceftazidime actually stopped an alternative to the natural coronavirus (pseudovirus) with comparable ability to infect from penetrating the cells and expressing the human ACE2.
What is the author’s recommendation?
The authors recommend this drug be considered for a treatment against SARS-CoV-2, the virus behind COVID-19. The drug is approved and has a known safety profile and as it’s generic and economical. They suggest that changes to chemical makeup of the molecule could be probed for optimization of inhibitory actions.
Chinese Academy of Sciences
The Chinese Academy of Sciences was formed in 1949 and is the national academy for the natural sciences for China. This agency functions as a national think tank and academic governing body and involves itself, including research in a number of societal affairs. It is purported to be the world’s largest research organization comprising around 60,000 researchers working in 114 institutes. It has been ranked as a top research organization. For example, Nature Index has ranked this agency No. 1 research institute in the world.
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