Image of spike protein of SARS-Cov-2 virus is shown with three small antibodies (pink)attached to its receptor binding domains. (From Physics Today, Vol. 73, No. 9, p. 22)
Even as Dotard Donnie - flailing in his re-election bid - dredges up false hopes for a premature Covid vaccine, researchers are hard at work trying to expand the treatment arsenal for dealing with this difficult disease. As reported in the latest Physics Today (Vol. 73, No. 9, Sept., p. 22) work continues at a feverish pace to find effective treatments. We already know about remdesavir, but that can't be the only weapon in the arsenal.
Now we learn that researchers at the University of Alberta have reported at the August meeting of the American Crystallographic Association that a "dipeptide- based protease inhibitor used to treat a fatal coronavirus infection in cats also blocks replication of the SARS-Cov-2 virus in samples of monkey lung tissue". Since monkeys are a closer mammal relative to humans than cats, this discloses a promising line of work.
The antiviral (known as GC273) works by blocking the function of the main protease denoted M pro . This is an enzyme that cleaves the polyproteins translated from viral RNA into individual proteins, i.e. once it enters human cells. We also now know, thanks to much more computational work, the sequence of how the viral spike protein attaches to the human cell host cell.
Basically, according to Kerstin Kleese van Dam - Director of Brookhaven National Laboratory's Computational Science Initiative (ibid.):
"When the spike is in its usual down or inward position, it is protected from the immune system. The spike becomes more vulnerable when it shifts to the up or outward position, required to enter the host cell."
This is good to know as it provides the key to at least controlling the virus using anti-virals. Indeed, the Alberta team has actually identified a pocket on the spike that changes shape during the transition from down to up. Also compound screening simulations "uncovered several molecules that might attach to the pocket and block cell invasion." According to van Dam:
"It's a bit like wedging a door open."
Joanne Lemieux, a biologist at the University of Alberta, asserts that GC273 has been shown to have no toxic effects on cats. Now, Anivive - a California company that develops pet medicines - has applied for a U.S. Food and Drug Administration approval to begin human trials with GC273.
Lemieux's group, after all, crystallized the Mpro in combination with the drug already and produced three-dimensional images (see graphic above) of how it binds strongly to the active pocket on the enzyme. Although GC273 should theoretically be effective in its current form, the Alberta team is planning further crystallography experiments at the Stanford Synchrotron Radiation Lightsource (SSRL) and the Canadian Lightsource to see if a reformulation could be optimized for human use.
What's the advantage? In the words of one Scripps Research associate, Ian Wilson:
"We'll be able to use smaller crystals, collect higher quality data, get a better signal to noise ratio and collect more data sets per hour."
All of which is badly needed in a media and political environment in which too many false claims are made for cures or treatments (e.g. hydroxychloroquine) and very little can be trusted - especially emanating from the Trump regime.
What we do know, based on the success of the GC273 research, is that the potential for effective Covid treatments must couple solid experimental and computational efforts as well as strict adherence to scientific testing and confirmation. We look, therefore, to empirical science to provide answers, not to already damaged politicians like Trump - who will lie or say anything to try to sneak into office again
Indeed, now that he's admitted (on tape) yapping to Bob Woodward that he's a criminal liar and fraud - who deliberately lied to the American people when he knew how deadly the virus is yet downplayed its risk - it may be all over but the dirges. At least we can hope so.
See Also:
https://www.folio.ca/antiviral-used-to-treat-cat-coronavirus-could-hold-key-to-covid-19-u-of-a-researchers/
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