HT team
As the Covid-19 pandemic torments the world, scientists in the US have made a drug that brings the virus’s downfall.
Chemicals in NMT5 drug can temporarily alter the human ACE2 receptor, the molecule the virus latches onto to infect cells, according to an article published in Nature Chemical Biology on September 29.
When the virus nears, its path into human cells through the ACE2 receptor is blocked. In the absence of the virus, ACE2 can function as usual.
“What’s so neat about this drug is that we’re turning the virus against itself,” said senior author Stuart Lipton a Step Family Endowed Chair and Scripps Research professor.
Molecular warheads
“We’re arming it with little molecular warheads that prevent it from infecting our cells. It’s our revenge on the virus.”
Though they have only studied the compound in animal models, the team is now making a version of the drug to evaluate for human use while carrying out additional safety and effectiveness trials in animals.
The virus has infected 614,385,693 people until September 30 and claimed the lives of 6.5 million, according to the WHO.
Before the COVID-19 pandemic, Scripps Research professor Lipton and his colleagues had been studying variations of the drug memantine, which Lipton developed and patented in the 1990s for treating neurological diseases like Alzheimer’s.
Memantine originated from an anti-influenza drug used in the 1960s. Clinicians began investigating it for other diseases after they noticed a woman with Parkinson’s symptoms improved when she took the pill for the flu.
The scientists tested a series of compounds, similar to memantine, with additional pharmacological warheads.
Two properties
They pinpointed the drug candidate designated NMT5 as having two fundamental properties: It could recognize and attach to a pore on the surface of SARS-CoV-2, and it could chemically modify human ACE2 using a fragment of nitroglycerin as the warhead.
The group realized this could turn the virus into a delivery vehicle for its demise.
“What’s beautiful is that this only knocks down the availability of ACE2 locally when the virus is coming at it,” Lipton said. “It doesn’t knock down all the function of ACE2 elsewhere in the body, allowing for the normal function of this protein.”
The drug also showed effectiveness against nearly a dozen other variants of COVID-19, including alpha, beta, gamma and delta strains.
Since NMT5 only uses the virus as a carrier, the researchers think the drug will likely be effective against many other variants of SARS-CoV-2.
