I would be interested in discussing this, and the other thread on Sanford has devolved into other topics. I would like to know if scientists may be biased on which strategies are most effective. Are we late to clinical trials for this drug?
While meltdown has been discussed largely in the negative context of a threat to small or endangered populations, it also has relevance in the positive context of inducing the extinction of a viral population within a patient. One drug in particular, favipiravir, has been demonstrated to inhibit the RNA-dependent RNA polymerase (RdRp) of RNA viruses (Furuta et al. 2013; Baranovich et al. 2013), and in vitro studies in influenza A virus (IAV) have specifically examined the relevance of a mutational-meltdown model in the presence of this inhibitor. Bank et al. ([2016 (https://www.nature.com/articles/s41437-020-0314-z#ref-CR1)), utilizing experimental passaging at different drug concentrations, described potential viral adaptation at low-concentrations. However, at higher concentrations, mutations accumulated at a nearly linear rate until a transition point was reached, at which a sharp increase in mutational accumulation was observed, followed by population collapse. Significantly, as opposed to targeting a specific genomic region, this input of deleterious mutations is a genome-wide effect, raining deleterious variants on all functionally essential genomic regions.
I don’t know. Assuming that disrupting replication works better than increasing mutation? I don’t know how scientists or doctors think. It just seems odd it wasn’t considered earlier except in other countries.
I found a website reference to a small trial in the U.S. in the spring but I haven’t had a chance to look up what the results were and if it was completed.
Preventing infections works the best. There’s no reason to develop treatments for a disease that will be controlled by a vaccine within the next 2 years. In addition, it’s hard enough to get everyone vaccinated. Imagine having to put everyone on a medication every time they are infected with a specific virus. That would be a massive logistical headache. It would be 10x harder than a vaccination program.
I really don’t know how to take this statement seriously. There is going to be a large portion of the public that are not going to take a two step vaccine every 6 months or whatever it’s going to be. There will still be those who it’s not effective for.
I’m talking about a medication for moderate to severe illness.
A whole lot of different therapies have been proposed for COVID-19 and clinical trials started for many of them. There’s no obvious reason that any one of them should be made higher priority than others, except perhaps for convalescent plasma (which doesn’t seem to do much) and monoclonal antibodies, both of which had a decent probability of being effective.
There was also little overall coordination or planning of what clinical trials should be started, especially in the US. Several factors contributed to this failure: 1) the problem of planning during the general confusion of a rapidly expanding pandemic, when many medical and public health people had to focus on other issues (e.g. getting testing working); 2) the highly fragmented nature of the US health care and research systems; 3) the near-total lack of Federal coordination of any aspect of this pandemic, and the muzzling of those agencies that might have provided more coordination by the White House; 4) the distraction caused by the completely unjustified hyping of hydroxychloroquine, which sucked attention away from many other possible clinical trials.
Not in the US that I know of, not that I’m a clinical trial kind of person. Individual hospitals or groups of hospitals started the studies I’m familiar with. The UK did vastly better, but they have a national health care system, and the WHO did some coordination, but we don’t want anything to do with them.
My point is that an anti-viral drug is not a viable replacement for a vaccine. You would also have to ask why people would be unwilling to get two shots every year, but would be willing to take another medication multiple times a day.
That’s true for every single vaccine. Thankfully, they don’t need to be 100% effective in order to shield a population
That’s a good point. I guess it is a question of how much money drug companies would want to spend on a clinical trial for even off-label use.
Favipiravir (also known as Avigan) is an antiviral medication approved in Japan and China for the flu. In vitro studies have shown that high doses of favipiravir were able to prevent human cells from being infected with SARS-CoV-2.
Two studies in China looked at how favipiravir worked in comparison to other antivirals. In a study of 240 patients in China with mild COVID-19 symptoms, 71% of patients given favipiravir recovered after 7 days compared to 56% who were given umifenovir (Arbidol). Another small study in China looked at 80 patients with mild COVID-19 symptoms and saw that that favipiravir helped to clear the virus faster than Kaletra (4 days vs. 11 days, respectively). The patients who took favipiravir also showed greater improvements in their lungs based on chest images. The first U.S. clinical trials for favipiravir were recently approved to start in Boston.
Small trials so far, but the more drugs that can be identified as effective, the better.
These are not mutually exclusive. Viral mutagenic therapies have been studied and utilized for at least the last two decades. Bold mine:
Remdesivir, is a nucleoside prodrug or nucleotide analog with potential efficacy against multiple viruses with sub micromolar range dose of administration. Nucleoside analogs (NAs) have been considered the most promising broad-spectrum anti-viral RNA-dependent RNA polymerase (RdRp) inhibitors and they have been effective in the treatment of multiple viral infections. Targeting viral replication within the host cell is one of the best anti-viral therapeutic approaches. These antiviral agents target viral replication enzymes. This could be due to their function as nucleoside analogs during viral replication that result in deadly mutations.
Ribavirin monophosphate interferes with viral RNA replication by inhibiting cellular protein inosine monophosphate dehydrogenase…Another possible antiviral mechanism for ribavirin is that it promotes lethal mutagenesis in viral RNA
You suspect that Favipiravir isn’t being properly investigated because the rest of the scientific community isn’t aware of genetic entropy. I want to make sure that you actually understand your suspicion related to Remdesivir (that has been discussed with you) and Favipiravir. The best way to check your understanding is to ask you to explain it.
So yes, I would like you to either explain the difference in the mechanism of action of the two drugs, or to retract your suspicion as insufficiently supported by your understanding.
As far as I understand it, here’s my kindergarten explanation, and you can tell me where I’m incorrect: they both inhibit the virus from replicating but in slightly different ways. Favipiravir possibly introduces more mutations (as a secondary result), but if that wasn’t valued as much may be assumed to be less effective otherwise?
I thought the abstract here sounded promising. They do say it’s novel and evidence has been limited.
Lethal mutagenesis has emerged as a novel potential therapeutic approach to treat viral infections. Several studies have demonstrated that increases in the high mutation rates inherent to RNA viruses lead to viral extinction in cell culture, but evidence during infections in vivo is limited. In this study, we show that the broad-range antiviral nucleoside favipiravir reduces viral load in vivo by exerting antiviral mutagenesis in a mouse model for norovirus infection. Increased mutation frequencies were observed in samples from treated mice and were accompanied with lower or in some cases undetectable levels of infectious virus in faeces and tissues. Viral RNA isolated from treated animals showed reduced infectivity, a feature of populations approaching extinction during antiviral mutagenesis. These results suggest that favipiravir can induce norovirus mutagenesis in vivo, which in some cases leads to virus extinction, providing a proof-of-principle for the use of favipiravir derivatives or mutagenic nucleosides in the clinical treatment of noroviruses.
No? Then the OP sure is puzzling. What did you mean by
What kind of bias do you suspect? Why would scientists not want to find anything that could possibly work? Why would you suspect scientists are avoiding checking out a potentially life-saving drug? What aspect of scientific behavior leads you to believe that there could potentially be bias against a life-saving drug during a pandemic? Are you still sure this is unrelated to your championing of GE?
We can talk more about RDRP inhibitors tomorrow, if you want. But if you’re going to make a claim about their difference, it would be best to make a guess based on evidence, not rhetoric.
That they just aren’t thinking outside of the box as much as they could. Also that the U.S. is intellectually superior perhaps. I’m definitely not saying that scientists wouldn’t want to find anything that could work - it’s a matter of what to prioritize as well. That’s perhaps what I mean - prioritization of certain avenues over others.