The first case of COVID-19 was reported in December last year. In the following few months, scientists proposed several drugs for the treatment of the disease. Drugs like remdesivir and favipiravir have been approved or given emergency use authorization while other drugs are still being researched.
Now, in two different studies, scientists have proposed two new ways to fight SARS-CoV-2 and COVID-19 .
In a study done at the University of South Florida, researchers have proposed drugs that can target both the entry and replication of the virus and another group of researchers at Cedars Sinai say that anti-inflammatory medications used for the treatment of inflammatory bowel disease (IBD) can be used to treat COVID-19 .
Killing two birds with a stone
The scientists at the University of South Florida looked for compounds that can target two crucial steps in the viral life cycle — the point when it enters healthy cells and when it replicates inside cells.
Building on their previous research, they found a few drugs that can target both these processes by attacking the human host protein cathepsin L, which is involved in viral entry, and the SARS-CoV-2 protein Mpro, which is important for viral replication.
Two compounds called calpain inhibitors II and XII, especially the latter, were found to be more effective against Mpro than another drug candidate called GC-376. GC-376 is a prodrug that is already being used to treat fatal feline coronavirus disease and had earlier been proposed to be a potential treatment against COVID-19 . Calpains are proteolytic enzymes that are involved in various processes in the body.
X-ray crystallographic studies indicated that calpain inhibitors fit perfectly into the binding sites of Mpro. Binding sites are specific sites on the structure of an enzyme where the substrate (the compound on which an enzyme acts) binds. Interestingly, once bound to the site, calpain inhibitor XII changes its structure so that it fits snugly into the active site. When the active site is taken, the enzyme cannot work.
Since the drug worked on both Mpro and cathepsin L, the researchers suggested that it can suppress drug resistance, which could occur if the virus mutates. Because even if the virus changes the Mpro structure, it would still need cathepsin L and vice versa.
IBD drugs for COVID-19
SARS-CoV-2, the COVID-19 causing virus, uses a host protein called ACE2 to gain entry into healthy cells. However, normally, this protein is also involved in the inflammation process. ACE2 is highly expressed in the lungs but also various others part of the body including the gut. There is an increasing amount of evidence that the novel coronavirus can use the GI (gastrointestinal) tract to enter body cells.
Building on these facts, the researchers examined records of 1,000 patients at Cedars Sinai in St Louis, Missouri, and several other centres across North America to study the factors affecting ACE2 expression inside the gut in patients with Crohn’s Disease and ulcerative colitis (two types of IBD) as well as non-IBD patients.
An inflammatory bowel disease is a group of disorders that leads to long term inflammation in the bowels, mostly colon and rectum.
They found that ACE2 expression in the colon was increased in the case of IBD and that these increased levels were associated with poor COVID-19 outcomes.
In both types of IBD patients, treatment with an anti-inflammatory drug called infliximab normalised the levels of ACE2 in the gut and improved COVID-19 outcomes.
However, the authors indicated that more research is still needed to better understand the process involving ACE2 and how it can be used to treat COVID-19 patients.
For more information, read our article on COVID-19.
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