The 3,250,000 cases of COVID-19 and 233,000 deaths caused by SARS-CoV-2 (numbers as of this writing) could have largely been prevented. The viral outbreak could have been stopped in December in Wuhan had we had the foresight and financial support to develop antiviral drugs or vaccines.
In the aftermath of the SARS-CoV pandemic of 2003, wildlife sampling taught us that bats harbor many SARS-like coronaviruses. Subsequent research revealed that some of these bat viruses have pandemic potential. We knew that CoVs lurked in bats in China with the potential to cause an outbreak. But no one would invest the money needed to make antiviral drugs or vaccines.
After SARS-CoV, a number of laboratories continued their research on the virus, but big Pharma lost interest in the virus – because it had disappeared from the face of the Earth. There was no money to be made in SARS-CoV antivirals or vaccines, so none were made. As a result, when SARS-CoV-2 emerged in late 2019, humanity was completely unable to stop its inexorable spread around the globe.
What could have been done? To start, we should have made antiviral drugs that inhibit a broad range of bat SARS-like CoVs. One protein encoded in the genome of these viruses – the RNA dependent RNA polymerase, essential for the synthesis of all viral RNAs – is the most highly conserved protein among all of these viruses. It would have been straightforward to take a sample of these RdRps from bat CoVs, produce them in cell culture, and find small molecule compounds that inhibit all of them. A pan-CoV antiviral drug could have been developed through human phase I trials, and stockpiled for the next pandemic. But there was no money to support such work – neither in the halls of big Pharma or forthcoming from the under-funded NIH.
It might have even been possible to make a pan-CoV vaccine, although in my view this would be much harder and less certain than a pan-CoV antiviral drug. One approach, similar to that being taken to make universal influenza vaccines, is to identify conserved epitopes (the amino acids to which antibodies are directed) on the viral spike protein. It would be straightforward to examine the spike proteins of many bat SARS-like CoVs to identify such conserved epitopes and either design vaccines to target them, or produce monoclonal antibodies agains such targets to be used therapeutically.
All of this research and more is taking place after the fact – too late to impact the pandemic. Companies are now motivated because the profit to be had is clear. Until such therapies are available – too late to impact the 2020 outbreak – we are left with testing antiviral drugs that were developed for other purposes, and they are not ideal. One that is being highly touted is Remdesivir, a drug that must be given intravenously (it is not sufficiently absorbed after oral administration) which means it is typically given only to very sick patients. By that time, virus loads in the lung are already low and giving an antiviral drug will have little impact. We could have had so much more than this.
How would all of this research have impacted the SARS-CoV-2 pandemic? In one scenario, we have stockpiles of a pan-CoV antiviral drug, enough to treat millions of people. When SARS-CoV-2 is first identified in Wuhan, the drug is immediately given a large phase II efficacy trial. We treat not only sick people but all their contacts and contacts of contacts. We also treat health care personnel. The drug will substantially drop virus levels in lung, impairing transmission. A larger phase III trial could follow with even more participants. It is likely that with such an approach, the virus would never have left China; but if it had, we could track it down and use the antiviral to stop spread. This scenario depends, of course, on extensive testing and contact tracing, a process not sufficiently done in the US and for which that country should be ashamed for not responding quickly enough.
It’s easy to blame bats for unwittingly giving humanity SARS-CoV-2. But I also blame both big Pharma and the US government for failing to come up with a pan-CoV antiviral or vaccine. Big Pharma because they are blind to anything that doesn’t enhance their bottom line. And the US government for severely under-funding the NIH so that essential research could not even be done in academic laboratories. It is very difficult to get money from Congress for research on a virus that is not a big human problem. That situation needs to end.
Every American should be outraged that the US has cut off funding for EcoHealth Alliance, an organization that supports wildlife sampling to discover viruses with pandemic potential in bats and other species. It is exactly that type of work that is needed to prepare therapeutics for the next pandemic. There is no scientific justification for such a move, only political motives.
I would also like to point out that due to pressure from a number of individuals who felt that determining the pandemic potential of SARS-like CoV in bats was too dangerous, a research moratorium on certain kinds of this research was imposed in 2014. I do hope the authors of that moratorium feel at least a small amount of regret as they look at the rising COVID-19 numbers. After all, Nature does not observe our moratoriums.
Now, as a consequence of this lack of vision, many people have died, economies have been destroyed, and the social structure of the world has changed. The US alone is spending trillions of dollars on recovery assistance. It would have been far cheaper to spend just billions for prevention.
Our model of how we make life-saving vaccines and antiviral drugs has to change. We cannot be dependent on for-profit companies and governments with lack of vision to save our lives. A new breed of non-profit organization is emerging that hopes to fund the development of vaccines and antiviral drugs that would not be otherwise possible. They include the likes of CEPI and READDI. Give them your support – our lives depend on it.
I would like to think that this pandemic will at least improve government support for research on viruses that are currently not harming humans, but have the potential to do so. But that would require that those in Congress who dole out the money look beyond politics. I do not think that will happen. Human health, and the viruses that impact it, will always be a political issue.
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Seconded! Nice post.
As someone who keenly followed the original SARS outbreak – and was followed across Canada by it as I travelled for conferences – I was amazed at the way interest in it just dropped off after the last case. Pretty much the same thing happened in 2009 after the flu pandemic, though: our country (South Africa) got all exercised about setting up capacity for making flu vaccines locally, then – nothing. That meant we had no capacity to respond to SARS2, or any other emerging disease agent, for that matter. Short-sighted stupidity.
Thanks for this post. I cannot agree more with your analysis. Same is thrue in France and there were no leadership of EU to build a common response either . This crisis highlights the failure of our systems driven by short sighted politicians (that can be in addition stupid) and companies. Sounds also paradoxical to live in countries were you get individual insurances for everyghing and not being able to invest in research as a common life and health insurance.
We get what we paid for…
Having said that: how do we move forward together and how we, as scientists and citizen can we help to re-build differently. Huge task ahaid…
Thanks Vince Racaniello
We can’t leave research for only pharma, governments Have got to fund virus research .
You really covered the whole scene
Thank’s a lot
Was looking for some mention of the lab in Wuhan and the possibility that SARS2-cov escaped there. Didn’t the U.S. invest $3.5 million into that lab?
Hello Professor Racaniello, thank you for this timely diagnosis. One clarifying question: when you refer to “pressure from a number of individuals” for the moratorium, are you pointing to the “Cambridge Working Group”? Or another group of people? http://www.cambridgeworkinggroup.org/
Thanks again,
Anthony Stavrianakis, medical anthropologist
I like this article very much. Thank you Sir
Under-Funded NIH research and lack of vision are both reflecting illegal and misuse of tax payers, again this pandemic could have been contained in China. There are multifactorial interdisciplinary reasons behind this pandemic spread globally. WHO is as well questionable on why the virus left China.
I entirely agree, Prof. Racaniello, thank you for your post.
The SARS-CoV-2 pandemic in no way proves that the moratorium on Gain-Of-Function experiments with infectious agents of pandemic potential was unwise.
(1) We did not need GOF experiments to tell us that zoonoses of an animal coronavirus had pandemic potential.
(2) Most GOF experiments with coronaviruses would not have permitted us to develop vaccines or therapeutics any faster than we are now doing. Consider what in hindsight would have been the most obvious GOF experiment with a bat coronavirus — insertion of a polybasic cleavage site. Acquisition of the PCS by SARS-CoV-2 almost certainly has been important for human-to-human transmission, but it’s not a useful target for vaccines and even if targeting the host-cell proteases that cleave the PCS proves to be useful, we didn’t need GOF experiments to tell us this.
(3) If we had done GOF experiments with animal coronaviruses and found the mutated viruses to be more transmissible in an optimized animal model, it is unlikely to have had sufficient influence to increase research funding and therefore would have not increased pandemic preparedness in the way that you envision.
(4) There’s a good argument that we should have invested more in pan-coronavirus drug development, but again, you don’t need GOF experiments for that. Maybe you need chimeric viruses for animal testing, but I don’t know if these qualify as GOF, and it’s not obvious to me that these are critical path experiments.
In summary, I still think the onus is on GOF supporters to provide solid and specific arguments that the benefits outweigh the risks.
I love your virology course. Thanks for all you do for humanity. You are an American hero.
It’s simple, block China from the rest of the F world, that country is responsible for all F viruses this last 2 decades,
If you target RdRps, then new resistant mutations would likely appear, right? Like you see in HIV protease inhibitors. And as this is a numbers game, chances for a mutation appearing is highly likely. If I remember correctly, one of the guests of your podcast, mentioned this known problem, in relation to the SARS-COV-2 protease.
Excellently put, Vincent. Thanks so much.
Nice blog Vincent. I’m alway reminded of the profound arguments for preparation that were made by Joshua Lederberg and Margaret Hamburg in 2003.
Very well said Prof, hope policy decision makers pay attention to what you have explained.
Great post.
I’m actually kind of curious why no one has tried throwing Echinaecia purpurea extracts at this thing. I get that it mostly works by encouraging an immune response, but there were a few NIH studies that mentioned it did have some effect on viruses directly.
Not sure if coronaviruses were among those tested though.
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This novel coronavirus is already one of that GOF…the so called humanist(!) scientists as you caused this pandemic disaster come to world…stop intervention into nature! What the hell you think you are??? Bill Gates says there will be more than 10 billion people on earth in 2120,so as a great philantropist he funds the vaccine works,just to decrease kid deaths..
Wow! What the heck are you Gates,that you dare to estimate human population and to take care of it ??? Are you god or what? So,dear professor,if you love to help people go feed those poors around you…
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If world were vegan there will be no pandemic. The greed for meat is the cause
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Vincent,
Thank you for writing this. I can’t stand for how little pharma cares about this outbreak. I’m leaving Merck because in some part they contributed to this lack of response by inaction in anti virals and their vaccine strategy is poor at best. Do you think intranasal delivery would improve redemvisvir bio availability? I know merck has had some compounds work very well this way. Keep up the fight! I’m fighting with you from U Penn.
Julia
A well-made case and one my virologist husband, Curt Horvath, and I have recently made as well at the Chicago Council on Global Affairs – on behalf not only of zoonotic disease but also crop disease, my area.
https://www.thechicagocouncil.org/blog/global-food-thought/guest-commentary-when-fighting-pathogens-pay-little-now-or-lot-later
As some readers here may know, tobacco mosaic virus was the first virus to be identified, and crop diseases pose significant threat to human well-being too. It’s clear that funding for human infectious disease is inadequate, but public and private funding for plant science in the US is on tenth of that for biomedical research – if that.
It’s clear in both cases that the answers we need for thwarting infectious disease come from more consistent support for research and application. The right financial incentives haven’t been there in the past, but Covid-19 might provide new ones.
The Pharma and politics didnt want spent some money at the right time and for that decission, the countries all around the world, are loosing thousands of lifes and trillions of dollars.
Root cause of problem is Chinese bat and other bizzare wild life eating habbits. Like north korea why cannot we completely shutoff trade travel and everything with china. Can we not dare to be bold? We will keep getting new viruses from china and then blane US govt and I harma
Incredible, well spoken and devastating!
Merci pour ce post. Je partage votre analyse. Travaillant pour un grand groupe Pharma, je suis toujours ému que nous ne faisions pas plus d’efforts scientifiques dans cette direction. La raison est financière, c’est le nerf de la guerre…
Thank you Vincent for your decades of work and for being the calming, rationale voice of science for so many during this chaos. In this hyper-politicized world it’s refreshing to read objective commentary that simply lays out the facts. Unfortunately, reading some of the comments it’s not sinking in with some of your readers/ listeners/ followers. There is no place for politics or nationalism in science or medicine… check opinions and beliefs at the door please
Vivimos engañados la gente común, todos pensamos; se nos dice qué, se gastan cientos de millones de euros, en investigación, yo me pregunto dónde se invierten, y donde los resultados, necesitamos trasparencia, tanto por la función Pública, ( nuestros gobiernos, como por la comunidad investigadora. Gracias por su exposición
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I see that Trump just (in 2020) stopped funding for the EcoHealth Alliance and Wuhan Virology Lab, the 2014 moratorium was on gain-of-function studies that people believed were for bioweapons research. NIH’s budget for 2020 is over $40 billion; it’s not clear how much would have been needed to continue SARS/MERS/ coronavirus research to develop pan-coronavirus drugs or pan-coronavirus vaccines. Big Pharma clearly will not invest any money unless they see immediate return potential; any scientist who worked in Pharma has seen projects dropped repeatedly after “the race” to the prize is lost (or the need disappears). Obviously an efficacious treatment for covid-19 would have been a goldmine, but that would require foresight and risk taking. The National Institute of Allergy and Infectious Diseases is Dr. Anthony Fauci’s branch of NIH; he clearly knows little about respiratory viruses, and would much rather spend more on a vaccine for AIDS, his specialty. He has given talks on pandemics but either his talks are just political, or the problem is too difficult. Or requires foresight and risk taking.
I absolutely agree that it would be nice to be prepared, worldwide, for coronavirus pandemic outbreaks.
However, the actual means is very unclear.
As far as I understand it – the SARS2/COVID-19 coronavirus utilizes an infection path which was not known to science until this disease exploded on the scene.
How exactly could a vaccine be created to combat this disease?
Even if SARS2/COVID-19 were not utilizing a novel infection path, it is still unclear just how feasible a “pan-coronavirus” anti-viral is.
In particular, what would be the costs and criteria to develop such an anti-viral? How would its efficacy be tested in the absence of a coronavirus which is both more lethal than flu and also highly transmissible?
Notice how Raniello completely forgets? to mention that there was a vaccine tested for SARS. The mice vaccinated with it developed cytokine storms when the mice were infected with SARS. I believe many died. Like he did report SARS went away so researchers did lose interest. This is similar to the dengue vaccine. It created cytokine storms in a subset of vaccinated. It caused dengue hemorrhagic fever symptoms in the affected children when they were post vaccination infected. The pharma companies responsible never acknowledged responsibility. I am certainly not going to get a vaccine for SARS COV 2. I am sure that in this panicked rush to create one they will not be adequately tested for safety. One knows there will be no long term safety studies. In fact no vaccines are subject to double blind actual placebo studies. What would normally be an inert saline solution for the placebo is in the case of the HPV vaccine is the vaccine without the antigen. Other vaccines safety studies used another vaccine as placebo.
What pandemic?
It is CoronaVirusHOAX
Very educational Tatiana….thank you…..please encourage The WHO and the world in general to fund unnecessary world hunger….again, thank you
Peter
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This analysis is a joke for not mentioning and completely missing the main reason for the spread of the virus around the world – the cover-up by the chinese government, who actively tried to do everything in their power for the information about it not to get out.
I noticed this article was published one day before Newsweek magazine went public with the information that the person that’s supposed to be leading doctor for the Virus Task Force, Anthony Fauci, spent $7.4 million of the taxpayers money to fund the “gain of function” research by the Chinese scientist at the Wuhan lab. This man is a fraud & a liar. The public had no idea that he was involved in paying people to create the very same virus that’s infecting us now. I’m no where near as smart about a virus as a lot of the people commenting on here, I’m just a regular working guy struggling to make ends meet. One thing I can tell you for sure is bombshell, nobody will believe a word Fauci says. I’ve noticed that none of the alphabet networks reporters haven’t touched this story but that’s ok, the public is aware of what he has done. Despite all the confusing scientific terms trying to explain that this virus occurred naturally, Fauci’s deceit proves that this is the man made virus that escaped from the Wuhan lab, infected millions, killed hundreds of thousands, was bought & paid for by Anthony Fauci & the Chinese government. What he has caused is criminal. The author of this article probably knows the truth about when & how the virus escaped. The sad part about this is nobody gives a shit that they have caused the deaths of all these people.
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Thank you. This applies to so much else also, human priorities have been and are very misguided to say the least.
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This article is BS. NIH and Eco-Health Alliance were doing unethical research called Gain of Function on this virus in Wuhan. It was the only place in the world where Fauci and the NIH could get away with doing this dangerous work. With Fauci’s recommendation the US government invest 7 Million dollars along with Eco-Health Alliance. These people, and the author of this article are the most dangerous psychopaths in the world!! Their Dangerous path to do Gain of Function on this virus has caused a world pandemic which has killed millions of people!! Great job Fauci and Eco-Health- Alliance.
Of the 3.25M patients, a dozen are mine. Antihistamines, anti-leukotriene (monteleukast), and Prednisone helped most, but an 18 yr old asthmatic almost died despite a very high Prednisone dose (120 mg/day). He responded dramatically after 3 doses of quercetin (1 gram every 12 hours), and has since come off all Prednisone and is tapering his quercetin dose down to 1 g/day. Quercetin couldn’t be safer; on the order of 100 mg/day is already eaten everywhere. It’s a specific inhibitor (Ki ~ uM) of the mast cell MRGPRX2 receptor, which binds and is activated by basic secretagogues like the viral nucleocapsid protein. Six of 7 amino acids at aa #369-375 are lysines. Another part of the protein is fat-loving (hydrophobic). The protein glues the negatively charged phosphate backbone of the virus’s RNA to the viral membrane. It appears to trigger IgE signaling through the Fc-epsilon-RI receptor without the need for IgE, technically called “pseudo-allergy.” The result can be anaphylaxis and death through what looks like an exaggerated asthma attack. My case report is in preparation; his PCR test was neg. His IgG test is pending.
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Someone years smarter than myself requested that I ask all of you this one question?
How did the polybasic furin cleavage site PRRA get into Covid-19?
Can anyone out there please answer this specific question?
Mark Mellow, your statement tells the entire story. Vincent Racaniello is part of a group of virologist writing articles to convince the public that this virus isn’t a man made. Mr Racaniello, please answer this specific question. How did the polybasic furin cleavage site PRRA get into COVID-19?
Did you notice that he has kept silent & never mentioned Anthony Fauci knowing about the funding of the Chinese researchers at the lab in Wuhan.
I didn’t want to think that this virus was released intentionally but too many things have happened that point to it. 9/11 took years of planning by our elected & permanent government officials & this situation appears to be the same. #1 has been the alphabet networks & their reporters, they all started out following the same script. Monday, March 9th was the first day the networks started their 24/7 coverage, it was like watching 9/11 over. I’m amazed that a majority are so stupidious not to realize that their fear & emotions is being used to make them compliant. The constant reference of “death” 24/7 on the TV screen, in news stories, experts predicting numbers, commercials, etc. Credit to the group that created the best psychological operation ever put together. The ultimate mind fuck, they got inside their heads & it’s still working. Brilliant!