COVID-19 usually attaches to human ACE2 receptor and infects cells, but this drug can attach to COVID-19. When the virus approaches the cell, the attached drugs can temporarily change the human ACE2 receptor, which means that the path of the virus entering the cell is blocked and ACE2 can work normally without the virus.
"The originality of this drug is that we are actually targeting the virus on ourselves." Stuart Lipton, the senior author of the paper, said, "We armed it with small molecular warheads and finally stopped it from infecting our cells."
Lipton and his team tested a compound library, which was similar to memantine in overall structure, but covered with additional pharmacological "warheads". They pointed out that the candidate drug named NMT5 has two key characteristics: one is to recognize and attach to the holes on the surface of COVID-19, and the other is to chemically modify human ACE2 with nitroglycerin fragments as warheads. This may turn the virus into a self-destructive transmission tool.
When the virus spreads in the body, NMT5 can be closely attached to COVID-19 particles; When the virus approaches ACE2 to infect cells, NMT5 will add a "nitro group" to the receptor. When ACE2 is modified in this way, its structure will temporarily change-about 12 hours, so that COVID-19 can no longer combine with it, thus avoiding infection.
The research team characterized and tested NMT5 in isolated cells and animals. In the cell culture experiment, the researchers tested the binding of Omicron mutant to human ACE2 receptor, which prevented 95% of the virus from binding. In hamsters with COVID-19's disease, NMT5-5 reduced the virus level to1100, which eliminated the vascular damage in the lungs of animals and alleviated inflammation. The drug has also been proved to be effective against more than ten other COVID-19 variants, including α, β, γ and δ variants.
The researchers said that it is expected that this compound will continue to be effective even if new variants appear, because it does not depend on the parts that usually mutate against viruses.
At present, the team is making another version of the drug to evaluate the effect of human use and conduct additional safety and effectiveness tests on animals.
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