12 ms·

I'm starting to get pretty optimistic. There seem to be a bunch of antivirals with very different mechanisms of action - this one blocks entry of the virus to c

I'm starting to get pretty optimistic. There seem to be a bunch of antivirals with very different mechanisms of action - this one blocks entry of the virus to cells, Molnupiravir fucks up accurate replication of the virus (nucleoside analog), others are protease inhibitors, which are very effective against HIV. There's a caveat, most treatments that look promising don't pan out, but there are a lot in the pipeline and it seems likely that some will. What I think will happen is a cocktail of antivirals, and together these will significantly reduce the mortality. We need that, because it looks like the virus will probably be circulating endemically. The other great thing about a cocktail (as opposed to a single antiviral) is that the virus developing resistance is both less likely and less of a problem if it does happen.

angelzen 5y ago
> Molnupiravir [interferes with] accurate replication of the virus At first glance this sound like a really bad idea, given that the #1 concern is future covid mutations.
- ralusek 5y ago
  It specifically causes non-viable mutations. Therefore, the concern isn't currently that it'll cause mutations in the virus and create new strains, but rather that we have to be very confident that it isn't resulting in mutagenicity in mammalian cells. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136050/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136050/
  - angelzen 5y ago
    Thanks, I wasn't aware of that.
ashtonkem 5y ago
mRNA vaccines look extremely promising too. It’s entirely possible that some classes of cancer will be effectively eliminated in our lifetime because of it, along with HIV and/or Malaria. The latter would probably be the biggest reduction in human death and misery since the invention of the Polio vaccine
- tombert 5y ago
  I've been saying for roughly a year now that if nothing else good can come from Covid, we at the very least are dumping a ton of time and resources and research into mRNA vaccines. I know basically nothing about virology, but I remember hearing a podcast a million years ago talking about mRNA vaccines, and I remember after it was over thinking "if this is even half as cool as it sounds to a lay person, the implications of this are huge". It appears that it's substantially more than half as cool as it sounded, and the fact that we are even having discussions about being able to wipe out malaria is mind-boggling to me (in a good way).
  - orra 5y ago
    We developed several working vaccines, and in record time. A triumph of scientific engineering. I too am very hopeful for mRNA vaccines, although I don't know how much I should temper my expectations. The idea of curing certain cancers, not just preventing them, is wild.
    - vibrato2 5y ago
      Except we had to change the definition of “working vaccine” to fit these new therapies. Traditionally a vaccine has to keep efficacy for a year. We haven’t got a year of data but the efficacy has dropped significantly
      - tombert 5y ago
        I don't know enough about vaccines to dispute what you're saying (though I feel like I have heard contrary data on this), but even if it's only fully effective for 8-9 months, isn't the fact that we had a vaccine that accomplished at least some of its goals safely designed and tested in record time a really cool thing? Even if it's only effective for 6 months, that's still 6 months of slowing the spread, and conceivably we can extend the efficacy by administering booster shots.
      - SketchySeaBeast 5y ago
        It's not as though the concept of a vaccine booster is new, after all we get annual flu shots. It's also a question of efficacy of the vaccine versus the new predominate variant. Delta didn't exist when the vaccines were finalized.
gizmo686 5y ago
A limiting factor for the effectiveness of anti-virals for Covid is time. Maximum viral load happens often happens before any symptoms are present, and the most severe diseases occurs weeks after infection as a result of the bodies inflammatory response instead of the virus itself. This means that by the time you know that a patient will have severe Covid-19, it is likely too late for any treatment that is based on interfering with the virus itself. Having said that, we have a good demographic understanding of who tends to get severe Covid-19, and a large testing capacity, so a cheap anti-viral treatment with few side effects could still be effectively deployed.
- beakerbreaker 5y ago
  That's a good point on the limitation, and to expand on your last point, an immediate demographic this could help is frontline healthcare workers and similar jobs who do get routine testing and are at higher risk in general.
  - mlyle 5y ago
    Yup. I'm a teacher and vaccinated. If I found out that I was exposed, and then tested positive... post-exposure prophylaxis sounds great. Also there's my dad, who has an immune condition due to old age. He's vaccinated, but who knows how effective the vaccine was for him. The existence of PEP could make it possible for him to do more at a similar level of safety... vs. the current option of staying in a small bubble for the rest of his life despite being otherwise able-bodied and capable.
    - grey413 5y ago
      FYI, your dad would most likely already qualify to receive the antiviral antibody treatments that have been given emergency authorization by the FDA. https://www.covid19treatmentguidelines.nih.gov/therapies/anti-sars-cov-2-antibody-products/anti-sars-cov-2-monoclonal-antibodies/ https://www.covid19treatmentguidelines.nih.gov/therapies/ant...
      - 5y ago
tim333 5y ago
Molnupiravir seems pretty good. I think in the trials eight people died in the placebo group, zero with the drug.
thehappypm 5y ago
It's almost like we're emerging into a world just like the world when antibiotics were invented, but for antivirals. We basically had just a small handful of treatments for viruses, now there's a huge pipeline all of a sudden. Maybe in the future, having effective antivirals for just about any virus will be the norm, not the exception.
lamontcg 5y ago
Mortality is going to be dramatically reduced once nearly everyone has T-cells+B-cells that recognize the virus. If everyone got vaccinated we'd be out of the pandemic phase and into the endemic phase with a virus that looked more like just a flu/cold. Vaccines are a 10x or 20x improvement in death and hospitalization rates. That's just a fact. All these antivirals won't have that kind of impact and are closing the barn doors after the horse has escaped. Which is not to say we don't research both, but vaccination is the simple easy and effective answer. There's a considerable technological fetish with antivirals while boring vaccines are now treated with skepticism, which is backwards. Antivirals should be used after vaccines have failed in vulnerable populations, the major weapon against viruses is vaccines, and they work.

angelzen 5y ago

> Molnupiravir [interferes with] accurate replication of the virus At first glance this sound like a really bad idea, given that the #1 concern is future covid mutations.

ralusek 5y ago
It specifically causes non-viable mutations. Therefore, the concern isn't currently that it'll cause mutations in the virus and create new strains, but rather that we have to be very confident that it isn't resulting in mutagenicity in mammalian cells. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136050/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136050/
- angelzen 5y ago
  Thanks, I wasn't aware of that.

ashtonkem 5y ago

mRNA vaccines look extremely promising too. It’s entirely possible that some classes of cancer will be effectively eliminated in our lifetime because of it, along with HIV and/or Malaria. The latter would probably be the biggest reduction in human death and misery since the invention of the Polio vaccine

tombert 5y ago
I've been saying for roughly a year now that if nothing else good can come from Covid, we at the very least are dumping a ton of time and resources and research into mRNA vaccines. I know basically nothing about virology, but I remember hearing a podcast a million years ago talking about mRNA vaccines, and I remember after it was over thinking "if this is even half as cool as it sounds to a lay person, the implications of this are huge". It appears that it's substantially more than half as cool as it sounded, and the fact that we are even having discussions about being able to wipe out malaria is mind-boggling to me (in a good way).
- orra 5y ago
  We developed several working vaccines, and in record time. A triumph of scientific engineering. I too am very hopeful for mRNA vaccines, although I don't know how much I should temper my expectations. The idea of curing certain cancers, not just preventing them, is wild.
  - vibrato2 5y ago
    Except we had to change the definition of “working vaccine” to fit these new therapies. Traditionally a vaccine has to keep efficacy for a year. We haven’t got a year of data but the efficacy has dropped significantly
    - tombert 5y ago
      I don't know enough about vaccines to dispute what you're saying (though I feel like I have heard contrary data on this), but even if it's only fully effective for 8-9 months, isn't the fact that we had a vaccine that accomplished at least some of its goals safely designed and tested in record time a really cool thing? Even if it's only effective for 6 months, that's still 6 months of slowing the spread, and conceivably we can extend the efficacy by administering booster shots.
    - SketchySeaBeast 5y ago
      It's not as though the concept of a vaccine booster is new, after all we get annual flu shots. It's also a question of efficacy of the vaccine versus the new predominate variant. Delta didn't exist when the vaccines were finalized.

gizmo686 5y ago

A limiting factor for the effectiveness of anti-virals for Covid is time. Maximum viral load happens often happens before any symptoms are present, and the most severe diseases occurs weeks after infection as a result of the bodies inflammatory response instead of the virus itself. This means that by the time you know that a patient will have severe Covid-19, it is likely too late for any treatment that is based on interfering with the virus itself. Having said that, we have a good demographic understanding of who tends to get severe Covid-19, and a large testing capacity, so a cheap anti-viral treatment with few side effects could still be effectively deployed.

beakerbreaker 5y ago
That's a good point on the limitation, and to expand on your last point, an immediate demographic this could help is frontline healthcare workers and similar jobs who do get routine testing and are at higher risk in general.
- mlyle 5y ago
  Yup. I'm a teacher and vaccinated. If I found out that I was exposed, and then tested positive... post-exposure prophylaxis sounds great. Also there's my dad, who has an immune condition due to old age. He's vaccinated, but who knows how effective the vaccine was for him. The existence of PEP could make it possible for him to do more at a similar level of safety... vs. the current option of staying in a small bubble for the rest of his life despite being otherwise able-bodied and capable.
  - grey413 5y ago
    FYI, your dad would most likely already qualify to receive the antiviral antibody treatments that have been given emergency authorization by the FDA. https://www.covid19treatmentguidelines.nih.gov/therapies/anti-sars-cov-2-antibody-products/anti-sars-cov-2-monoclonal-antibodies/ https://www.covid19treatmentguidelines.nih.gov/therapies/ant...
    - 5y ago

tim333 5y ago

Molnupiravir seems pretty good. I think in the trials eight people died in the placebo group, zero with the drug.

thehappypm 5y ago

It's almost like we're emerging into a world just like the world when antibiotics were invented, but for antivirals. We basically had just a small handful of treatments for viruses, now there's a huge pipeline all of a sudden. Maybe in the future, having effective antivirals for just about any virus will be the norm, not the exception.

lamontcg 5y ago

Mortality is going to be dramatically reduced once nearly everyone has T-cells+B-cells that recognize the virus. If everyone got vaccinated we'd be out of the pandemic phase and into the endemic phase with a virus that looked more like just a flu/cold. Vaccines are a 10x or 20x improvement in death and hospitalization rates. That's just a fact. All these antivirals won't have that kind of impact and are closing the barn doors after the horse has escaped. Which is not to say we don't research both, but vaccination is the simple easy and effective answer. There's a considerable technological fetish with antivirals while boring vaccines are now treated with skepticism, which is backwards. Antivirals should be used after vaccines have failed in vulnerable populations, the major weapon against viruses is vaccines, and they work.