RNA dependent RNA polymerase =RdRp
It's the enzyme that uses the viral RNA template to make viral RNA and is pretty much unique to viruses. There are enzymes that can do this in animals but they are very tightly regulated and quite different from the viral enzymes. that's what makes them such a good target for drug design.
Just a comment about drug design - it's part science part craft. There are computational methods for guessing what might work if you know the 3D structure. And there are clever screening methods that can find fragments of compounds that you can stick together to get better binding. But there is a huge amount of trial and error involved as well. And when you have something that works in your screen you then need to figure out if it works in cells and mice and humans.
The SARS-CoV-2 genome is not converted to DNA during viral replication. It’s RNA to RNA.
Meep right you are. It does still mean the virus uses an RNA template to make the RNA strand which is the unusual step that doesn't really exist in humans.
It’s not immediately obvious why some of them inhibit viral enzymes and not enzymes our cells use.
The reason is the enzyme that incorporates them is different from any of the host enzymes - that difference is enough to develop an analog that affects one enzyme but not the other. And yes you can make such analogs that are immensely toxic to humans.
I still can’t get my head around what the endgame of a virus is –
Hi Ian, you can't anthropomorphize this, it's just a virus. It evolved in bats and exists now because it is well adapted to the bat biology. Bats have a very different immune system that allows them to tolerate many more infections with little harm.
In humans this virus just replicates the same as it did in bats. It doesn't have an endgame or aim. It could wipe out all humans and then die off itself and it wouldn't "know". And it's ancestor would still exist in bats.
TLDR entirely reasonable that these drugs work
also science funding is good
It's highly likely any effective treatment protocol will involve a nucleotide analog for reasons noted in the main post.
It's worth noting treatments for viral diseases are uncommon because the immune system handles viruses very very well.
That means most treatment attempts are likely to come after the immune system has done it's job.
For viral diseases where for one reason or another you can't wait for the immune system we rely on vaccines - again essentially relying in the immune system.
Where neither of those options are available the treatments focus on bits of biology that are different between the virus and the host - that usually means targeting the enzymes that replicate the viral genome or process the viral protein. Both of which use mechanisms that are not present in humans and hence are reasonable targets for drugs (since they won't kill the host).
One of the best targets is the genome replication enzymes because they do something that is very uncommon in humans - convert RNA into DNA - this means the viral enzyme that does that can be blocked without harming the host. Nucletotide analogs are king amongst these. Cold sore creams, real ones not the fake homeopathic ones, contain acyclovir which is a nucleotide analog that kills herpes virus.
The problem is most of these nucleotide analogs are cheap to make and many of them cure the disease so no long term treatment is required. That's why big pharma don't bother with them - because the profit is piss poor.
This is another reason why you should harass your local MP into funding government funded research - because that's the money that funds people like Siouxsie Wiles.
Totally agree Hebe.
As a cyclist the shared paths have always been a nightmare. You never know if the dog will stay put or if the child will decide to run across the path in front of you and pedestrians can turn on a dime much quicker than a cyclist can avoid.
The idea that they should be forced into one space is another consequence of the planners dedication to the the car. No-one, not cyclist, not pedestrian, not scooter, not even a bus can be allowed to restrict the car. And so all us unimportant humans get shoved into one tiny space that we share to the best of our ability. But it doesn't work.
And now in the time of lockdown I avoid all the bike paths and ride on the roads because with fewer cars they are spaces I can ride with ease and all the pedestrians on the paths can walk without worrying I might not be able to stop if they wobble or step in an unexpected direction.
I would say that my bell (a Kong) seems to be easier to hear - except if the person has their headphones on :(. It's a lower pitch and easier on older ears.
One thing I hope will happen is that so many people are discovering they really can walk or cycle to the local market and they might just continue.
Cars are useful and valuable, but we've seen them dominate beyond their real value - no small part because of huge marketing by the car industry.
This enforced, slower world of lockdown has given people a chance to see that the car isn't as necessary as they thought.
And there's also the extra sense of community walkers and riders have, we wave and nod and say hi in a way that you just don't get in a car and now everyone is experiencing that community. Maybe just maybe it will last.
Nice to see the community popping up again. Be nice to see a few more of the old faces here too.
Without wishing to be depressing I wanted to link this article.
It’s been doing the rounds and is pretty clear on what is guesswork and what is known which is a refreshing change.
We’re stuck at home doing some work stuff as we can. Concentration is utterly shot. Hopefully we’ll be allowed in to work to prevent some of our precious plants from dying but for now we’re locked out.
Anyway stay safe all.
I have a mixed response to XR.
They are absolutely right that climate change is an urgent problem and I feel and can empathize with their frustration that our (corrupt?) political systems and the politicians themselves are doing nothing to address the biggest and worst contributors to climate change.
They are certain AND they are right that something has to change before more people are harmed.
But it isn't an approach I would take and I can see that to some extent their actions can make it harder for some politicians to change.
Stopping public transport is unbelievably stupid but dissent and disruptive dissent is called for now because our political system has failed.
XR isn't the route I'd choose or recommend but perhaps it is the only way to change our political path.
Cannabinoid receptor agonists
That would be the correct term.
But since defining three words each time you describe the drug seems a little much I suspect it wont catch on.
Bart, are you saying that you won’t buy access to a bundle of great journalists because you’d prefer separate contracts for each of them?
No I'm saying I don't want to pay the demonstrably evil pimp based of his promise that he'll keep paying those working journalists (yeah right).
You know if they had like a collective that I could pay without involving the pimp then I'd be keen.