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UGA research team cracks corona, clears way for drug

At last, we are well on a potential rapid development path to generating PLpro-targeted therapeutics for use against SARS-CoV-2, thanks to UGA's rational approach in medical research.

NEW DELHI, June 12: The New Coronavirus has devastated the world with its ferocity and speed but it is surprising to learn that it is less lethal than the SARS. Its mortality rate is low! On June 12, there were 76,09,728 confirmed cases globally and 4,24,084 deaths. That is a mortality rate of 5%. In 2002-03, according to the WHO data, there were 8,098 SARS cases and 774 deaths. That is a mortality rate of 10%.

(But it is not the moot question here whether, following Darwin's theory of evolution, PLpro has been modified (made less lethal) by nature to give the virus a better chance to coexist with the humans and not destroy the host. Unlike of what we think about the epidemic as being most fatal.)

This is the presumption from where the Georgia university's research team, led by Scott Pegan, director of Center for Drug Discovery, started off at a steady trot. It has found that this is because the PLpro protein, needed by all coronas for (1) replication and (2) to debilitate the host immune function, is less effective in SARS-CoV-2 vis-a-vis suppressing the human immune system. That is why, fortunately, it is not so fatal, unlike what we think.

“The PLpro from SARS-CoV-2 behaved differently than its predecessor that caused the SARS outbreak in 2003. Specifically, our data suggests that the SARS-CoV-2 PLpro is less effective at its immune suppression roles,” said Pegan, professor of pharmaceutical and biomedical sciences in the College of Pharmacy. “This may be one of the underlying reasons why the current virus is not as fatal as the virus from the 2003 outbreak.”

Now that the UGA has cleared the path, it should not be taking much longer to find a drug to denature the new coronavirus, rather than depending on elusive vaccine candidates.

Move on to Stage II: The team began exploring inhibitors designed to knock out PLpro and stop the replication of the virus. They have stumpled upon some pre-existing combos and are eyeing a therapeutic development to strike at the PLpro. Narrowing down to naphthalene-based PLpro inhibitors, they have taken the research to near-conclusion.

Therefore, we are well on a potential rapid development path to generating PLpro-targeted therapeutics for use against SARS-CoV-2, it is so projected.

"Our hope is that we can turn this into a starting point for creating a drug that we can get in front of the Food and Drug Administration,” so dreams Scott Pegan.

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