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Coronavirus

As the world knows, we face an emerging virus threat in the Wuhan coronavirus (2019-nCoV) outbreak. The problem is, right now there are several important things that we don’t know about the situation. The mortality rate, the ease of human-human transmission, the rate of mutation of the virus (and how many strains we might be dealing with – all of these need more clarity. Unfortunately, we’ve already gone past the MERS outbreak in severity (which until now was the most recent new coronavirus to make the jump into humans). If we’re fortunate, though, we’ll still have something that will be worrisome, but not as bad as (say) the usual flu numbers (many people don’t realize that influenza kills tens of thousands of people in the US each year). The worst case, though, is something like 1918, and we really, really don’t need that.

Coronaviruses, which are rather large single-stranded RNA viruses, are nothing new in human disease. They are, in fact, the most usual one cause of the common cold, so all of us have been infected with who-knows-how-many different coronavirus strains over the years. Generally that’s what you can expect from them: a mild, irritating respiratory infection, and in fact I’ve been fighting off just such a thing for several days now myself. Such things are generally in the upper respiratory tract, but some of these viral infections can move on to bronchitis or pneumonia, either primary (viral infection in these areas) or secondary (opportunistic bacterial infection that develops as a sequel). I had secondary bacterial pneumonia in both lungs a few winters ago, and I give the experience 0 out of 5 stars. I was extremely glad that antibiotic therapy knocked it back down so quickly (the improvement was dramatic), and I have no trouble at all picturing how pneumonia in general has managed to kill off so many people over the centuries.

All sorts of creatures have their own suite of coronaviruses infecting them, and every so often one jumps into a new species. Humans seem to be more vulnerable to viral infection from other mammals (naturally) and from birds. No one is sure what species 2019-nCoV came from, although all the evidence is that it started in a particular market in Wuhan, likely from direct blood transmission in some sort of butcher shop. The virus appears to cause a rapidly developing viral pneumonia in some patients, and the problem with that is that there is very little to be done. Supportive care is all there is to offer – as medical professionals continually remind the general public, antibiotics are useless against viruses. And although we have more actual antiviral agents than we used to, the selection in hand is not very useful against the coronaviruses. So what does biopharma research have to offer?

There is no way that a new antiviral small molecule can be discovered and developed in time to help anyone in the near future. That sounds rather pessimistic of me, but it’s true. Extremely fortunate and rapid development of such an agent would cut the lead time down to just a few years; that’s the time scale we’re looking at, and there’s no guarantee that any such drug can be found at all. No, the chances for a more rapid response come down to the biologics: a vaccine, or treatment with (say) monoclonal antibodies. (Update: here’s an overview at Biocentury on what’s going on). Extremely fortunate and rapid development of either of those would still be on the scale of many months, and if this viral outbreak is seasonal (as they tend to be) that would mean that there is nothing that’s going to arrive in time to help this season’s victims. But it also buys some time for the next round, if you want to look on the bright side.

Here’s a look at antibody therapy against MERS, to give you the idea. Manufacturing such things on scale is not trivial, but could be done. The biggest obstacle to using Mabs as therapy in this situation is their selectivity (which is also, of course, a great strength of antibodies under the right circumstances). Mutational escape is always a possibility, so ideally you’d want several antibodies at once, each targeting a different epitope and thus lowering the chance of the virus mutating its way out of the spotlight. But that makes development correspondingly more difficult.

And as this article at Science shows, vaccine development is already underway. Moderna, Inovio, and the University of Queensland are mentioned as working with the Coalition for Epidemic Preparedness Innovations (CEPI), and there are other companies who are cranking up their own efforts. It would seems quite likely that a vaccine can be developed, and the earlier work on the SARS and MERS coronaviruses will help these efforts out. But vaccines need to be tested, in animals and then in humans, and you are of course looking (as you always do with a new therapy) for safety and efficacy. You don’t want to set off nasty immune responses – the immune system is terrifying when aroused inappropriately. And you also don’t want a vaccine that the virus can evade easily by mutating some protein on its surface. A vaccine is just a way of doing endogenous antibody therapy (rather than giving a monoclonal one from outside), and the same considerations apply – raising response to several epitopes and/or known variants at the same time is the best strategy when you can manage it. Manufacturing such a vaccine on scale would be the next challenge, one that everyone involved is well aware of, and the effectiveness of a coronavirus vaccine would be partly determined by how many millions of people we would need to vaccinate.

That takes us back to the open questions about the spread of the virus. For news on this and other issues, Stat has been doing a good job rounding up the reliable information, and they’re doing it in front of their paywall. Here’s one of their latest, on the shift from trying to contain the virus to dealing with the fact that it may be too late for that strategy to work.

The signal/noise on this whole story has been suboptimal, as well it would be, so it’s important to have good sources.  Vast amounts of junk information have already been circulating. For one thing, no, this particular virus was not patented in 2015, and it is not some engineered bioweapon. There are no “natural” cures or preventatives that you can buy from friendly merchants trying to sell you some. I have been forwarded clips of what are purportedly Chinese workers spraying some sort of white stuff around to supposedly block the spread of the virus, but this is also spurious – there are no virus “disinfectants” to spray around, and we’re not even sure how this virus is most likely to be spread. The best preventatives that we know of are dull stuff like avoiding getting sneezed on, not going around shaking hands with everyone, avoiding large confined crowds of people, and other basic public hygiene points. I rather doubt that face masks help much (although they certainly don’t do any harm), since we don’t know how this virus spreads and what sort of particles it might spread on. (And besides, a lot of the air that you breath while wearing one of those standard white face masks is coming from around the sides of the mask, anyway).

So that’s about as far as we can go with the information we have. A developing story, indeed, which calls for avoiding panic on one end and complacency on the other. The advent of new infectious diseases is a test of our civilization’s technological ability – let’s pass it.

121 comments on “Coronavirus”

  1. Hap says:

    Would masks decrease droplet transmission or do droplets stay aloft (and meander around) too long for them to work?

    1. SirWired says:

      Given that few mask-wearers are likely to have it fitted properly, and changed at the correct (rather short) intervals, masks mostly serve to reduce your infection of others; they are limited-to-no effectiveness in protecting you from contagious illness.

      (When fitted properly and changed at the prescribed intervals, they are quite effective in keeping you from getting sick, but that would be rare indeed among the general public.)

      1. Hap says:

        Well, lowering the spread would help, even if it doesn’t help me directly.

        1. Sergio says:

          Nine years ago, movie about the coronavirus epidemic came out.
          Name: Cantagion (2011) – Link bellow:

          http://gomovies.asia/watch/9mxyW0dN-contagion.html

      2. T says:

        Some experts have speculated that they might indeed provide some protection, but mainly though discouraging you from touching your face (mouth and nose), which is a major route of infection. Having worn these things in the lab, I can well imagine how they would be of little use against aerosols because it is quite difficult to draw air through them, so unless they are very well fitted, you just end up sucking air around the sides of the mask (especially around the bridge of your nose).

      3. Edward Boss says:

        The journal of virology in 2014 wrote this about the use of protease inhibitors. cut/paste: We found that although mutations that confer resistance arise quickly, the resistant viruses replicate slowly and do not cause lethal disease in mice. Overall, our study provides the first analysis of the low barrier but the high cost of resistance to a CoV 3CLpro inhibitor, which will facilitate the further development of protease inhibitors as anti-coronavirus therapeutics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178758/

    2. Andrew says:

      There’s a big difference between surgical masks and legitimate respirators.

      Your typical loose-fitting surgical masks only serve to protect others from the droplets created by your coughs and sneezes, they aren’t effective at protecting the wearer. As Derek mentioned, the air you breathe is just gonna take the path of least resistance and go around the mask.

    3. DrOcto says:

      In eastern cultures it’s also common for people that have the flu to wear a mask to protect the people around them.

    4. Martin says:

      I believe masks work more on a basis of social good, than they do for individual protection. As in any potential carriers of a virus are much less likely to broadcast spray droplets into the air if they are wearing a surgical or dust mask.

  2. lexc says:

    Speaking of small molecules, I don’t know much about anti-retroviral targets and how homologous they are between HIV and this coronavirus but there are reports that the Chinese health authorities are recommending the use of antiretrovirals as treatment against the current coronavirus infection.

    1. Dionysius Rex says:

      Sounds like a neat way to accelerate the emergence of highly resistant mutants.

    2. Frank says:

      It doesn’t hurt to try in this dire situation, but more evidence of efficacy is needed.

    3. Dr. Manhattan says:

      It’s a positive strand virus and doesn’t have a reverse transcriptase to make a DNA copy. So, the RTIs would not have any impact. The virus has been sequences (Coronaviruses are not very big, around 23-30 Kb) and it is related to SARS, but with some differences in the spike proteins.

      1. Chemist says:

        All viruses have to replicate their genomic sequences whether dna or rna using a polymerase of some sort and so are potentially vulnerable to nucs. Targeting these polymerases is usually among the best strategies to achieve an antiviral effect. See for example, the use of ribavirin to target hcv, an RNA virus. I expect screening known antivirals from every class is the first stop for many researchers looking an antiviral for this coronavirus.

  3. luysii says:

    Having a son, daughter in law and two grandchildren living in Hong Kong, I’ve followed this very closely. A few days ago, the virus had spread to 29/31 of China’s provinces. There is no way the virus won’t escape China. So far the mortality is about 3.5 % (80/2800), as usual affecting the very old and those with pre-existing disease (again the very old).

    To follow the epidemic, likely soon to be a pandemic, you can’t do better than the South China Morning Post — here’s a link to their website — https://www.scmp.com, and a very scary post this morning from the dean of one of the med schools there —
    https://www.scmp.com/news/hong-kong/health-environment/article/3047813/china-coronavirus-hong-kong-medical-experts-call

    1. Bell4 says:

      Seems like the lethality rate may be higher than that, if you compare the total # of fatalities to the # number of patients who have recovered and been released from care. That ratio is currently about 1:1. The early patients are probably sicker than average, so the mortality rate is certainly lower than the 50% figure implied by this oversimplified comparisons. Nevertheless, the true mortality rate will not become clear until we have a lot more data on # of fully recovered patients.

      1. SirWired says:

        We don’t have nearly enough data to determine the true fatality rate right now. We can guess at a fatality rate for the hospitalized, but it is highly-likely that there are many for which the illness is no more dire than a bad cold. Those patients will never be recorded in any census of the disease.

        We can guess that most deaths from this illness will make the official statistics (okay, assuming the local authorities cooperate), but without taking a large population sample, it’s not really possible to determine the true infection rate, and therefore the mortality, expressed as a percentage of the total infected.

        1. luysii says:

          SirWired. Exactly. The best example is polio. For every paralytic case, 100 people either had mild GI disease or nothing at all.

        2. anon says:

          The census of cases outside China is probably more complete because even people with mild illness, who have been in China recently, are likely to be tested. There have been no fatalities among the 100 or so confirmed cases outside China, so this also suggests that the true mortality might be lower than 3 %.

  4. Brorona says:

    The people will survive
    In their environment
    The dirt, scarcity, and the emptiness
    Of our South

    The injustice of our greed
    The practice we inherit
    The dirt, scarcity and the emptiness
    Of our South

    There on the beach
    I could see it in her eyes
    I only had a Corona
    Five cent deposit

    1. Peter Clark says:

      Long live D Boon

  5. MTK says:

    Is there any chance that some existing drug might have unknown antiviral activity?

    My thought is you screen them and maybe get lucky and find one that works at doses that have already been clinically tested.

    1. penicitius says:

      Get everyone on antibiotics RIGHT NOW

      1. Dr.Manhattan says:

        From Derek’s post above: “Supportive care is all there is to offer – as medical professionals continually remind the general public, antibiotics are useless against viruses.”

        Which part of this do you need to have slowly explained?

        1. sgcox says:

          penicitius post was a sarcasm, I am 99.9% sure

          1. Student says:

            And the last 0,01% are the cases where antibiotics are actually working (by a non placebo mechanism).

        2. Nominal says:

          Cringe,,,

        3. Reziac says:

          Possibly relevant: something we learned from the early stages of the parvovirus epidemic was that high-dosing the sick puppy with any antibiotic that came to hand greatly reduced secondary infections, and reduced mortality from ~90% to ~25%. (And the sooner treated, the better.)

          Even tho a compromised lung is not nearly the bacterial stew that is a compromised gut, I do wonder how many deaths from viral pneumonia are, similarly, secondary sepsis.

      2. Obvoius comment says:

        This is why we need to stop using this word altogether. There are antibacterials and antivirals. “Antibiotic” simply means against life which is way to general to be useful.

        1. Martin says:

          the word “antibiotic”, in both common and medical usage, means “antibacterial”. Going back to the root of the word to in an effort to broaden the meaning is merely playing semantics.

      3. Dave says:

        Lol.. yah right…

    2. An Old Chemist says:

      AbbVie’s HIV Drug Aluvia Seen as Potential Treatment for Coronavirus
      https://www.biospace.com/article/abbvie-to-donate-hiv-drug-to-china-as-potential-treatment-for-coronavirus/

      1. Dr. Manhattan says:

        The coronavirus does have a big polypeptide that doesn’t need to be processed by a protease similar to the situation with HIV. The question is how close are the two proteases and will there be inhibition by an HIV protease inhibitor of the coronavirus protease? Also, would this act to readily select resistant mutants?

        1. Dr. Manhattan says:

          Should read “Does need to be processed”. Spell “correction” can be a bitch at times…

      2. loupgarous says:

        Thanks for the link! I noticed, however, that efficacy data as we know them here are non-existent:

        “The decision to use AbbVie’s medicine came after a noted respiratory expert at Peking University First Hospital in Beijing said he was given the HIV drugs to fight the virus after he contracted it following a visit to Wuhan, the capital of Hubei province in central China where the virus is thought to have originated. Wan Guangfa came down with the virus after interacting with coronavirus patients. He told China News Week that the HIV treatments worked for him.”

        So, a noted respiratory expert employed by a Beijing university hospital recovered from Wuhan coronoavirus, but seems to have succumbed to the post hoc, ergo propter hocfallacy.

        It’s reasonable to say “I had this therapy because its mechanism of action against HIV might also work against coronavirus”, but not so reasonable to extend the thought to “and it worked, because I’m no longer ill” with respect to a virus that kills a few percent of people who seek medical help, but only makes some other people ill for a few days. The guy reporting his cure by a protease inhibitor cocktail (ritonavir’s only there to block cytochrome P450 3A4, extending the serum half-life of the other protease inhibitor lopinavir) might owe his cure to his immune system making antibodies to the coronavirus

        1. cynical1 says:

          You had the same thoughts I did but, for whatever reason, there is data that suggests that at least some HIV protease inhibitors inhibit the corona virus SARS in culture for whatever reason. Here was a reference I found in Google Scholar from 2004.

          https://doi.org/10.1016/j.bbrc.2004.04.083

          1. loupgarous says:

            Thanks for the reference. With n as low as it is for protease inhibitors in Wuhan coronavirus, we’ll have to wait a while. Hopefully AbbVie’s $1 million worth of lopinavir/ritonavir pills will be given to in a way that patients’ responses can be tracked usefully. It’d be nice if humanity caught a break during a pandemic.

  6. mm says:

    “Coronaviruses, which are rather large single-stranded RNA viruses, are nothing new in human disease. They are, in fact, the most usual cause of the common cold, so all of us have been infected with who-knows-how-many different coronavirus strains over the years.”

    Not a major point in this article for sure, but I always thought Rhinoviruses are the most common cause of the common cold. Wikipedia seems to agree with me and further states that there are only seven known human coronavirus strains (of which SARS, MERS and 2019-nCoV are three).

    1. MereMortal says:

      I was about to say the same thing. The statement that coronavirsuses are the most usual cause for the the common cold is one of the misinformations that is being spread in media at the moment. They only represent +- 15% of common cold infections.

      Ironically Derek tweeted that getting good information is crucial.

      1. Old Timer says:

        I like that people help Derek fact-check his posts, but geesh.

    2. Jeff says:

      The article was corrected, and now has “the most usual” crossed out.l, replaced with “one cause” … of the common cold.

  7. Elena Angela Lusi says:

    2019 Wuhan Novel Coronavirus

    It may be too late to wait for a vaccine to stop this epidemics. In the meantime, could we use pooled immunoglobulin from the plasma of the thousand infected subjects who developed immunity against the virus and adopt a passive immunotherapy for compromised patients acutely deteriorating.

    Elena Angela Lusi, Immunologist

    1. x says:

      I don’t work on purifying antibodies from plasma, but since we don’t know what antibodies we’re looking for, is there a standard method for scooping out all the unknowns from pooled plasma and leaving behind, say, red cell antibodies? Adsorption or something?

    2. Reziac says:

      Here’s a weird cross-effect possibly of interest, which has not been officially studied but works very well in the field (I’ve personally observed it):

      Dogs infected with canine distemper virus can be reliably and rather abruptly (12-24 hours) cured by dosing them with serum from donor dogs injected with Newcastle vaccine, or if time is short, the actual Newcastle vaccine. Yes, this is a vaccine for chickens.

      https://www.edbond.com/antidistemper.html

      Note that Dr.Sears recommends a week of antibiotics to combat secondary pneumonia.

    3. John Heithaus says:

      I don’t see why you couldn’t try pooled Ig from recovered patients. I don’t think there would be any need to specialize the formulation. Just standard protocols from the likes of CSL Behring. The problem at this point is the limited number of recovered patients.

  8. John Hsieh says:

    Johns Hopkins Center for Systems Science and Engineering (CSSE) has a very useful website to track Wuhan virus:
    https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6

  9. electrochemist says:

    Just wanted to mention that (contrary to the narratives being spun in the media), the US has undertaken several research and development initiatives to prepare for viral pandemics. For example, the Duke University Human Vaccines Institute has major DARPA funding for its Pandemic Prevention Platform (P3). Their stated goal is to be able to develop therapeutics “capable of halting viral pandemics within 60 days” (from start to small scale GMP mfg).
    [See: https://corporate.dukehealth.org/news-listing/duke-institute-tapped-build-rapid-response-system-viral-pandemics%5D

    I saw a seminar presented by the Director of the Duke Regional Biocontainment Labs last year, and he mentioned that antisense oligos are one of the areas they are exploring to get around the long development times for small molecules and antibodies.

    Not sure how involved that group is in this current episode (but I assume they must be).

    1. As2O3 says:

      That might actually work, a metabolite (GS-441524) is already sold on the grey market for use against feline infectious peritonitis – and being hailed as a miracle cure.

    2. JeffC says:

      Worth a whirl. They are all RNA viruses so there’s a chance. The Gilead compound originally came from one of their RSV programs so it does appear to have broad activity (or too depending on your viewpoint). It is a bit of a surprise that despite very promising (if not spectacular) preclinical data in Ebola it failed completely clinically in the field. So there’s obviously something a bit odd here about the compound. But if it has activity in vitro then it at least appears to be fairly safe based on the Ebola data. Worth a shot.

  10. v-deg says:

    Did anyone think to make virus degraders? Vi-Degs?

    1. NewYearChemist says:

      Interesting idea, v-deg. But degrading viral targets may be even more challenging than for regular human targets. Viral enzymes get multiplied in each infected cell by the gazillions – probably difficult to degrade them all efficiently.

      1. Hap says:

        And if we’ve incorporated viral DNA into our genome, it might be hard to avoid off-target effects.

  11. Christophe Verlinde says:

    According to the BBC’s news site “The number of people killed in China by the new coronavirus has risen to 81, with almost 3,000 confirmed ill.” To put that in perspective, in a serious epidemic year the flu causes about 50,000 deaths in the USA. So far, there is no reason for the panic that the media help create in this country.

    1. x says:

      There are some indications that there might be in fact 50000 infections already. Chinese authorities have lied on these before.

    2. Barry says:

      The time to initiate research on a cure is long, long before a disease reaches steady-state. This is the toe of the exponential epidemiology. It is not time to panic; it is time to engage seriously

  12. Anonymous says:

    Laurie Garrett is the author of “The Coming Plague: Newly Emerging Diseases in a World Out of Balance,” published in 1994.

    Four months before the appearance of the first case of this virus in humans in Wuhan, in Sept 2019, Laurie Garrett published “The World Knows an Apocalyptic Pandemic Is Coming; But nobody is interested in doing anything about it.” as a short article in Foreign Policy magazine: link in my handle.

    Will this become one of those 50 million – 100 million death pandemics? Even if not that deadly, what will be the costs of treating the infected and protecting the uninfected? (Garrett says $3 T or more.)

    1. x says:

      Sounds like some alarmist hooey with just enough scientific-sounding jargon to sell it. Might as well ask Nostradamus in that case.

    2. James Millar says:

      No more impressively prophetic than a stopped clock.

  13. Anonymous says:

    Readers would be blown away by how much virus research is influenced by cancel culture mccarthyism-style politics. Right now, in the highest offices of the NIH and other HHS agencies, there are lawyers who have never done kab work in their lives, making day-to-day decisions about who should or should not keep their research programs based on perceived ” medical colonialism “, ” racism”, or other charges.

    1. Tom Ames says:

      Yes! This is the REAL THREAT TO PUBLIC HEALTH!!!!1!!!

      I would be interested in subscribing to your newsletter!!!

      1. Chris Phoenix says:

        Tom, I would have LOVED your comment MORE THAN ANYTHING if only it had been SARCASTIC!!!1!!!!1!!!

    2. Nat says:

      As is increasingly the case these days, I can’t tell if this is serious or a poorly-formed attempt at satire.

  14. Chris Phoenix says:

    A quick search says that monoclonal antibodies tend to be developed by artificial evolution. Thus they may hit a target that’s easy to evolve away from.

    Is anyone working to sequence antibody-producing immune cells from people who have successfully fought this virus? Presumably they would have a section of DNA that coded for an effective antibody.

    Of course, you might have to sequence a lot of cells, so this would have to be a recent technique.

    1. DrOcto says:

      I’m not sure that you understand how the immune system works.

      1. johnnyboy says:

        Or DNA…

    2. artificial chemist says:

      is artificial evolution the next big thing after artificial intelligence?

  15. Curious reader says:

    Are there any common parts of (corona)viruses that could be targeting by a universal mAb or vaccine?

  16. John Thacker says:

    “although all the evidence is that it started in a particular market in Wuhan,”

    Although a paper just published in The Lancet provides some clinical evidence for the theory that it started earlier outside the market in question and was brought in, where it spread.

    https://www.sciencemag.org/news/2020/01/wuhan-seafood-market-may-not-be-source-novel-virus-spreading-globally

    1. A Nonny Mouse says:

      There is a government biological laboratory about 6 miles from the market which has been looking at SARS, among other infections.

      Maybe something could have happened there and someone took it out!

      1. loupgarous says:

        “There is a government biological laboratory about 6 miles from the market which has been looking at SARS, among other infections. Maybe something could have happened there and someone took it out!”

        That might explain this . Those who’ve traveled far by car and had a heavy meal enroute know “Who farted?” is always a plausible excuse.

    2. student says:

      Out of curiosity, why is it important to figure out where the virus originated? Does it really matter whether the virus came from the market itself or 6 miles from the market?

      1. Barry says:

        The market is not just a coordinate in space. It is a suite of practices, housing animals of many species in close proximity w/ poor sanitation. Knowing the origin, we can make rational decisions to reduce the chance of another such pathogen emerging.

        1. Tim Bergel says:

          Not to mention that if we can find the species the virus came from, we have an animal model to test treatments on.

      2. loupgarous says:

        If “six miles from the market” happens to be “a laboratory culturing novel strains of coronavirus”, it suddenly becomes very important. Just saying.

  17. rfb says:

    The virus binds to human cells by attaching to the enzyme ACE2. I know that several big pharma had ACE2 programs back in the ’90s. Maybe one of the small-molecule ACE2 inhibitors will alter the enzyme surface enough to prevent virus binding? According to Wikipedia, the marketed ACE1 inhibitors don’t work against ACE2, so it would have to be a molecule designed specifically for ACE2.

    1. Bannem says:

      Losartan . . .

      1. Benoit says:

        ABR or ACE inhibitors could be great for mitigating the loss of ACE2 lung endothelium cells.
        They have been tried for pulmonary artery hypertension, maybe even for acute respiratory distress syndrome.

        1. Semmelweis says:

          ACE probably mediate vessel/endothelial damage via released of nitric oxide, sartans losartan, irbesartan and telmerisartan can block some of this effect. Adding a lipophilic statin like atorvastatin, simvastatin or lovastatin can give more protection and reduce the havoc.

          Azitromycin also has some antiiflammatory properties that could help control inflammation. There is now evidence monoclonal antibodies work for coronavirus.

          Both antivirals and monoclonal antibodies where a total disaster during the Ebola epidemic so it is bit strange to harp on about that.

          M.D. Tropico

      2. cynical1 says:

        According to what little I read, the corona viruses use the Angiotensin-converting enzyme 2 (ACE2), which is a metallopeptidase, as a receptor for infection. The sartans inhibit the ACE1 (AT1) receptor (which is a 7TM and not an enzyme) and are usually also many thousand fold selective over the ACE2 (AT2) receptor which is also a 7TM and not an enzyme. Since the corona viruse’s spike proteins use ACE2 enzyme as a receptor, I’m guessing that one would not observe a direct antiviral effect with that class of drugs. Further, from what I understand the ACE1 carboxypeptidase inhibitors like captopril and enalopril don’t inhibit the ACE2 enzyme either. In fact, as far as I know, there aren’t any ACE2 enzyme inhibitors on the market and even if there were I would guess that the virus would have to bind at the active site of the enzyme for an enzyme inhibitor to inhibit viral replication.

        1. Magnus Dominans says:

          Cynical,
          Maybe your are correct, but sartans have “proven” benefit in ARDS.

          It sounds like you are studying car engine to solve problem of traffic jam seems related but understanding the car engine does help solve the problem of traffic jams.

          Point being; Sartans can be protective without being specific, as they protect the host and can keep endthelium intact by other mechanisms.

          Anyways why look for a total new AT2 blocker when they already exist?

          M.D.

          1. Carol Howard says:

            Could arbs and ace inhibitors be a cause of lethality in the coronavirus? They cause up regulation of Ace2 cells allowing more damage to be done??

  18. Carol Sue Vander Brook says:

    Just this: https://foreignpolicy.com/2020/01/26/2019-ncov-china-epidemic-pandemic-the-wuhan-coronavirus-a-tentative-clinical-profile/

    “One puzzling aspect so far is the thankful lack of child victims. Usually, children, with less developed immune systems than adults, come down with one illness after another. A particularly severe example is RSV viral pneumonia, which results in an estimated 118,200 child deaths annually. (Adults are not seriously affected.)

    Yet few children have yet been reported with coronavirus symptoms. That does not mean that no children have been infected. A similar pattern of benign disease in children, with increasing severity and mortality with age, was seen in SARS and MERS. SARS had a mortality rate averaging 10 percent. Yet no children, and just 1 percent of youths under 24, died, while those older than 50 had a 65 percent risk of dying. Is being an adult a risk factor per se? If so, what is it about childhood that confers protection? It may be the nonspecific effects of live vaccines such as for measles and rubella, which already have been found to provide protection from diseases beyond their immediate target. That may also explain why more men than women have been infected by the coronavirus, because women routinely are given a rubella vaccine booster in their teens to guard against the dangers of having rubella while pregnant. While we wait for an accelerated coronavirus vaccine to be ready, could innate immunity in adults be boosted by giving measles vaccines?”

    1. Paulo Barrera says:

      Definitely a possibility !! I’m with you

      1. Sylvie Aubert says:

        i am with you too! And the more data about the number of cases Did anyone look into it? WHO data on immunization with MMR and other vaccines can be found here:
        https://apps.who.int/immunization_monitoring/globalsummary/timeseries/tscoveragemcv1.html
        I have plenty of other resources if someone is in the position to make this idea heard.
        Take care

    2. Sylvie Aubert says:

      I am with you! And the more data about the number of severe cases in the different age groups we get, the more convinced I am about this possibility. It would also explain the differences between countries. Did anyone look into it?
      WHO data on immunization with MMR and other vaccines can be found here:
      https://apps.who.int/immunization_monitoring/globalsummary/timeseries/tscoveragemcv1.html
      I have plenty of other resources if someone is in the position to make this idea heard.
      Take care

  19. Concerned Citizen says:

    Recently this article came out in a website called Zerohedge:https://www.zerohedge.com/health/man-behind-global-coronavirus-pandemic

    It basically accuses the Chinese government of accidentally releasing a virus that they had engineered to become a bio-weapon. I wondered, could this be verified independently?Here is what I found:
    As early as 2009, China took the extraordinary step of denying reports that it has bio-weapons capabilities:https://www.voanews.com/archive/china-denies-us-report-it-has-biological-weapons-capabilities

    A novel Corona virus was first identified in mid-2012 – samples were taken from a patient in Saudi Arabia and sent to a lab in the Netherlands for examination:https://www.theguardian.com/science/2013/mar/15/coronavirus-next-global-pandemic

    These samples were then sent to the Canadian National Microbiology lab in Winnipeg, Canada for further study and investigation in 2013:https://www.winnipegfreepress.com/local/coronavirus-being-studied-in-winnipeg-207500931.html

    In 2014 an academic paper review viral transmission was released, one of the co-authors was a certain Dr(a) Xianggo Qiu:https://www.ncbi.nlm.nih.gov/pubmed/25059478

    Meantime, in 2016, China decides to create its own virology centre of excellence in the city of Wuhan:https://www.nature.com/news/inside-the-chinese-lab-poised-to-study-world-s-most-dangerous-pathogens-1.21487

    Then in July, 2019, two Chinese scientists working at the lab in Winnipeg was expelled, citing “irregularities” in relation to their work. One of them was a certain Dr(a) Xianggo Qiu:https://www.cbc.ca/news/canada/manitoba/lab-researcher-rcmp-national-microbiology-lab-1.5212851

    interestingly, the article from CBC in the link immediately above states that she “… received her medical degree from Hebei Medical University in 1985 and came to Canada for graduate studies in 1996. She is still affiliated with the university there and has brought in many students over the years to help with her work.”
    Dr(a) Xianggo Qiu is credited with helping find a treatment for Ebola and so is a very capable scientist:https://ppforum.ca/articles/dr-xiangguo-qiu-dr-gary-kobinger-against-all-odds-they-discovered-a-treatment-for-ebola/
    https://www.researchgate.net/profile/Xiangguo_Qiu

    As recently as August, 2019, concerns about China’s bio-weapons capabilities were again raised:https://www.nationaldefensemagazine.org/articles/2019/8/2/viewpoint-the-tools-and-threats-of-synthetic-bioweapon-development

    The question is, did Xianggo Qiu or some of her students somehow manage to get samples of the coronavirus over to the lab in Wuhan, where it was then accidentally released?
    I cannot find any evidence for this. But the idea is certainly a very intriguing one…
    If so, it means that the study below is just “cover” for what actually happened; and is another example of how scientific journals may be fooled:
    https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.25682

    1. Derek Lowe says:

      I find this sort of connect-the-dots stuff unconvincing. Zerohedge is a conspiracy-theory site, for starters. It would not surprise me in the least to know that China has engaged in bioweapons research, but I see no reason to believe that this virus is anything of the kind. It is extremely similar to other previous coronaviruses, and its sequence shows no signs of human engineering.

      1. Curious says:

        I agree that bioweapon theory is unlikely, but just curious, how what signs of human engineering do you mean in the sequence? Engineered point mutations to previous coronaviruses (say SARS) can look the same as naturally occurred, right?

      2. varvar says:

        You should not dismiss concerned citizen’s comments out of hand. Conspiracy or not, a Chinese national was arrested at Boston airport just a month ago attempting to smuggle to China some “biological samples.” For Heaven’s sake, this guy tries to take presumably live material in his personal baggage from research lab here TO CHINA!! Wake up, stop being an ostrich…SOMETHING STINKS IN THE STATE OF DENMARK…
        “Zaosong Zheng, 30, a Chinese national, was arrested on Dec. 10, 2019, at Boston’s Logan International Airport and charged by criminal complaint with attempting to smuggle 21 vials of biological research to China. On Jan. 21, 2020, Zheng was indicted on one count of smuggling goods from the United States and one count of making false, fictitious or fraudulent statements. He has been detained since Dec. 30, 2019.”
        see full indictment here for more startling “connect the dots..”!!!!!!!!!
        https://www.justice.gov/usao-ma/pr/harvard-university-professor-and-two-chinese-nationals-charged-three-separate-china

      3. varvar says:

        What is the latest? Today is Feb 20 and the story has been quietly buried by the news media and the establishment! Why no updates about one of the most important stories in Science, namely the chair of one of the most prestigious departments in most prestigious university in the world with an annual budget the size of Switzerland arrested and appears in “jump suit”!
        –my previous post Feb 4 repeated for emphasis, connect the dots…connect the dots…someone please connect the dots (everywhere)!
        You should not dismiss concerned citizen’s comments out of hand. Conspiracy or not, a Chinese national was arrested at Boston airport just a month ago attempting to smuggle to China some “biological samples.” For Heaven’s sake, this guy tries to take presumably live material in his personal baggage from research lab here TO CHINA!! Wake up, stop being an ostrich…SOMETHING STINKS IN THE STATE OF DENMARK…
        “Zaosong Zheng, 30, a Chinese national, was arrested on Dec. 10, 2019, at Boston’s Logan International Airport and charged by criminal complaint with attempting to smuggle 21 vials of biological research to China. On Jan. 21, 2020, Zheng was indicted on one count of smuggling goods from the United States and one count of making false, fictitious or fraudulent statements. He has been detained since Dec. 30, 2019.”
        see full indictment here for more startling “connect the dots..”!!!!!!!!!
        https://www.justice.gov/usao-ma/pr/harvard-university-professor-and-two-chinese-nationals-charged-three-separate-china

  20. Cb says:

    What about non-specific covalent inhibition of the Coronavirus cysteine protease (3C-like protease) for only a couple of days (when the viral load increases). E.g. the cysteine may be covalently inactivated with dimethyl-fumarate (DMF) : up to ~500mg/day oral dose seems to be allowed hitting all sorts of cysteines : (registered as Tecfidera; MS patients can take it for much longer periods). Hard for the virus to become resistant: no specificity pockets would be occupied using DMF and Cyst mutation is suicide. Do not expect severe immunosuppression using DMF for only a couple of days

    1. M.D Tropico says:

      Maybe, but as this has two stages, a first state that is with little symptoms and helps spread the virus and then it seems to make people much more sick around day 10 and by that time it may be to late or less effective to intiate treatment.

      I suspect you will need treatment minimum 10 days, probably 2- 3 weeks more likely.

      And I do suspect the main side effect, loose stools may make DMT less of a favorite.

      ACE2 blocker like losartan is better bet at this point and more easily available.

      1. Cb says:

        LOOKING for Coronavirus Cys Protease inhibitor rapidly available at large scale!.
        Dimethyl fumarate is a cheap chemical ~60$ for 100gr 97% purity. This price is much, much lower than going for the extremely expensive Tecfidera for MS containing this simple chemical (drug prices…uhhh). Probably, dimethyl fumarate is not the safest and best coronovirus cys-protease inhibitor available, but on the one hand not many if any drugs have been registered with this activity and on the other hand a selective cys protease inhibitor and scaling it to production takes a couple of years. Allicin and or diallyl-disulfide from Garlic: these nasty substances should inhibit coronavirus cys proteases…….also not a convenient cure available in a few months. Interestingly, the reactive metabolite of the analgesic acetaminophen (paracetamol): NAPQI is also a non-specific cys protease inhibitor. So a couple of well established drugs with reasonable safety is available which may inhibit the 3C-like viral cys protease irreversibly….and the garlic molecules of course. Would be interested to see what the IC50 of all these substances is and if it is within a realistic range.
        Making an ACE2 blocker on large scale is not easy either and Losartan is not an enzyme ACE blocker but a AT-II gpcr receptor antagonist……

        1. M.D. Tropico says:

          1. Agree DMT is cheap and available, not bad option as they also keep endthelium tigth to avoid. So could be scaled up quickly.
          2. From ARDS case reports sartans have shown benefit.
          3. Sartans, statins can save the host while host/victim can developed natural immunity.
          4. I think SARTANS can be available quite fast, at least if we trust current number of affected. Angiotensin 2 is not only a receptor, but also bio-active protein, but also often associated with worse outcome in many infections and other pathologies.

          You seem to know more about the actual receptor so I can not argue, but I feel its worth looking what known drugs including sartans and DMF could do the job, via ACE2 or proteinases.

          But hopefully medicine/science will provide best option/answer free of bias one way or the other.

          I feel these biotech “start-up” solutions often strangely endorsed WHO makes no sense.

          I do not claim to know the truth but is open to listen and hear new points of view.

          You know the saying “God help search for the truth, but spear me company of those who found it.” Not pointed at you rather a general reminder to stay open for learning, surprising and ideas, not necessarily agree with them but at least see if they could be of use.

        2. kurt says:

          Very curious about your garlic/allicin comment. I generally have good luck with it for infections. Are you saying it could be useful or a bad thing to be taking for coronavirus? I wouldn’t want to do anything that would INCREASE the number of ACE2 receptors. I’m very glad there are people out here who are knowledgeable.

        3. Stephen Redmond says:

          I have no idea if it will work on Covid19 but after 2 years of chronic URTI, my immunosupressed son hasn’t had one in months after starting him on flavinoids and Allicin. Quercetin, Chinese Skullcap and Allicin all have antiviral properties and Chinese Skullcap was used for some patients as a Traditional Chinese medicine antiviral in Wahun.

      2. Kathy Reade says:

        I just learned about blood pressure patients being at such extreme virus risk from an Adult Congenital Heart Disease Assn webinar on Monday. I take a “rescue cocktail” including Irbesartan. Does this mean I should continue it, or is it a conduit for the virus to go into the heart? I am terrified and my cardiologist has cancelled me over and over waiting for rox coupler approval…

        1. Derek Lowe says:

          Not an MD myself. But no one has yet recommended that people taking a “sartan” drug go off of it.

  21. saf says:

    Nice article was worth reading. thanks for information
    This is also nice.
    https://techcers.blogspot.com/2020/01/what-is-coronavirus-new-threat-to-world.html

  22. Christophe Verlinde says:

    Based on the data shown in the BBC article “Coronavirus declared global health emergency by WHO” (see:https://www.bbc.com/news/world-51318246), I came up with an exponential function that gives a doubling rate of 2.0 days. This rate predicts that by Feb 28 ALL of Chinese citizens will have been infected, very unsettling. That’s why the Chinese government is pursuing massive quarantine measures.For reference, a google search revealed a doubling time of 2.3 days calculated by professional epidemiologists (doi: http://dx.doi.org/10.1101/2020.01.23.20018549) – only slightly less catastrophic. I herewith my earlier comments that there is no reason for panic yet.

  23. Richard McHale says:

    Apropos of nothing, the word “preventative” bothers me – how did that extra “at” invade the perfectly adequate word “preventive” and convert it into self important tongue litter??

    1. loupgarous says:

      The same guy who gave us “inflammable” for “flammable”, or his great-grandson, the commentator on televised football games who uses “defense” as a transitive verb.

  24. Michèle says:

    I had a really bad virus once that couldn’t be cured with antibiotics. I ate raw garlic cloves (probably a good 3-7 pieces per day) and chased them with a large glass of OJ (it’s gnarly AF but it worked) plus I got lots of sleep and rested…I just stayed in bed the entire duration, and I was better within 5 days!! No meds and no antibiotics (the doc wouldn’t prescribe them)….

    1. Cb says:

      Interesting one person trial with desired effect 😉 Earlier in this blog I hinted at the possibilty of non-specific covalent inhibition of Coronavirus cysteine protease with the drug dimethyl-fumarate. Garlic delivers other covalent inhibitors (activity in low-micromolar range) of cys proteases such as Allicin and diallyl-disulfide. How much garlic should be consumed to get inhibitory levels and is there any standarizarion of Allicin content in garlic apart from nasal detection of these smelly substances

    2. Derek Lowe says:

      If you really did have a viral infection, though, antibiotics would have been of new use at all. They kill bacteria, and they target bacterial pathways that viruses just don’t have. And depending on the virus, you might have felt better within 5 days even without the garlic and OJ. Resting up and getting plenty of liquids is always a good plan, anyway.

      1. AT says:

        Garlic has been a big blessing for my family . It fights not only bacterial, but also viral & fungal infections . Since I found this out , I have taken 1 or 2 cloves of garlic a day plus Vit C when ill, and have not been to the doctor in years .Garlic usually knocks infection out within a few days. And amazingly, last year , a family member took a couple garlic cloves daily plus mega doses of vit C for the flu & was completely well in 24 hours. It has been awesome not to have to deal with the effects of prescribed antibiotics or getting so sick from viruses! Very thankful to God for natural remedies !

  25. MCS says:

    For what it’s worth, here’s a nicely done, periodically updated summary (in the handle). I simply don’t trust any number coming from the Chinese government, even if they are trying to be straight, the chain from ground truth to the mouthpiece in Beijing is hopelessly unreliable.

    As someone who has never needed to even see a doctor for “flu”, the unknowable number of people infected that never sought out a doctor seems key. There are likely a number of fatalities that innocently won’t make it to the statistics assuming there is no systematic cover-up going on.

    The cost has already been staggering, no doubt we are about to see the inception of another indeterminable war on virii.

  26. Venkatesh says:

    Garlic can cure corona virus . Make a garlic into juice and lightly boil it and mix with 2 tea spoon of honey and drink it 1 litre water 50 grams of garlic . First it will irritating and second it will cured .it’s a ancient herbals. I cured 24 people still now

    1. OilSnake says:

      1 liter of sweet garlic water? I think I’d rather have the coronavirus thanks.

  27. Eddie says:

    Venkatesh,
    Can you tell us more about this please? Serious request. Where did you ‘cure’ and what was the situation?

    Thank-you

  28. jean says:

    I would like to join in

  29. Wkw says:

    Totally missed in all this commentary, surprisingly, is the antiviral and immunomodulatory potential of host defense protein / peptides and esp their Mimetics… optimized for safety/efficacy. This is where the anti-SARS-Cov-2 answer may come. Labs in Asia and in the Middle East have been advancing this research for a while, inc showing activity agains SARS-CoV-1 and MERS.

  30. Wayne says:

    Apologies in advance, member of public here on. Ibersartan ARB I’m getting confused and worried bu the contradiction within the scientific community about the medication im taking!. The Lancet and BMJ are saying that such medications possibly increase the severity of the Covid-19 and it’s ability to bind to the ACE 2 which are more numerous due to taking ARBs?. Then other researchers are suggesting that ARBs are a possible direction of fighting this dreadful virus which is completely the opposite of what the BMJ and Lancet are staring. Anyone explain what is the best way forward for me as a patient on these medicines

    1. Derek Lowe says:

      I think I’ll do a post on this issue; it’s confused a lot of people!

      1. Wayne C says:

        Please be our guest, it would help to alleviate this confusion.

  31. Wayne says:

    Apologies in advance, member of public here on Ibersartan ARB. I’m getting confused and worried bu the contradiction within the scientific community about the medication im taking!. The Lancet and BMJ are saying that such medications possibly increase the severity of the Covid-19 and it’s ability to bind to the ACE 2 which are more numerous due to taking ARBs?. Then other researchers are suggesting that ARBs are a possible direction to look at fighting this dreadful virus?. which is completely the opposite And a contradiction of what the BMJ and Lancet are stating?. Could anyone explain what is the best way forward for me as a patient on these medicines

  32. Jeff Ulrich says:

    I have the same question – seems to be conflicting info out there. BMJ and Lancet are both highly respected sources and they seem to be saying sartans could make it worse. So one side says worse and the other says it could be a treatment?

  33. There’s nothing to worry about corona virus, as this is an imaginary disease formulated by the perpetrators in exchange of greed for power, huge money, and depopulation, according to Dr. Lorraine Jeanette Day, a US author, former orthopedic trauma surgeon and Chief of Orthopedic Surgery at San Francisco General Hospital and promoter of alternative cancer treatments. Formerly, she’s also an adviser at Center for Disease Control & Prevention (CDC)

    I’m sharing this to help people to lessen fears.

    According to the Doctor, viruses and bacteria do not cause a disease but these serve as a clean-up crew which regulates intakes/abuses of the human body. She said that all doctors are aware of this as this is published in medical literature.

    You may check this video which I uploaded in my youtube account, for more details.

    https://www.google.com/url?sa=t&source=web&rct=j&url=https://m.youtube.com/watch%3Fv%3Da9bQFSqZHGM&ved=2ahUKEwiP2Y_C2KPoAhVGyYsBHbfkCWkQwqsBMAF6BAgFEAc&usg=AOvVaw3iZ1AQEBz7UQB-r_-KUxIs

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