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Genomic Study Points to Natural Origin of COVID-19

Posted on by Dr. Francis Collins

COVID-19 Update

No matter where you go online these days, there’s bound to be discussion of coronavirus disease 2019 (COVID-19). Some folks are even making outrageous claims that the new coronavirus causing the pandemic was engineered in a lab and deliberately released to make people sick. A new study debunks such claims by providing scientific evidence that this novel coronavirus arose naturally.

The reassuring findings are the result of genomic analyses conducted by an international research team, partly supported by NIH. In their study in the journal Nature Medicine, Kristian Andersen, Scripps Research Institute, La Jolla, CA; Robert Garry, Tulane University School of Medicine, New Orleans; and their colleagues used sophisticated bioinformatic tools to compare publicly available genomic data from several coronaviruses, including the new one that causes COVID-19.

The researchers began by homing in on the parts of the coronavirus genomes that encode the spike proteins that give this family of viruses their distinctive crown-like appearance. (By the way, “corona” is Latin for “crown.”) All coronaviruses rely on spike proteins to infect other cells. But, over time, each coronavirus has fashioned these proteins a little differently, and the evolutionary clues about these modifications are spelled out in their genomes.

The genomic data of the new coronavirus responsible for COVID-19 show that its spike protein contains some unique adaptations. One of these adaptations provides special ability of this coronavirus to bind to a specific protein on human cells called angiotensin converting enzyme (ACE2). A related coronavirus that causes severe acute respiratory syndrome (SARS) in humans also seeks out ACE2.

Existing computer models predicted that the new coronavirus would not bind to ACE2 as well as the SARS virus. However, to their surprise, the researchers found that the spike protein of the new coronavirus actually bound far better than computer predictions, likely because of natural selection on ACE2 that enabled the virus to take advantage of a previously unidentified alternate binding site. Researchers said this provides strong evidence that that new virus was not the product of purposeful manipulation in a lab. In fact, any bioengineer trying to design a coronavirus that threatened human health probably would never have chosen this particular conformation for a spike protein.

The researchers went on to analyze genomic data related to the overall molecular structure, or backbone, of the new coronavirus. Their analysis showed that the backbone of the new coronavirus’s genome most closely resembles that of a bat coronavirus discovered after the COVID-19 pandemic began. However, the region that binds ACE2 resembles a novel virus found in pangolins, a strange-looking animal sometimes called a scaly anteater. This provides additional evidence that the coronavirus that causes COVID-19 almost certainly originated in nature. If the new coronavirus had been manufactured in a lab, scientists most likely would have used the backbones of coronaviruses already known to cause serious diseases in humans.

So, what is the natural origin of the novel coronavirus responsible for the COVID-19 pandemic? The researchers don’t yet have a precise answer. But they do offer two possible scenarios.

In the first scenario, as the new coronavirus evolved in its natural hosts, possibly bats or pangolins, its spike proteins mutated to bind to molecules similar in structure to the human ACE2 protein, thereby enabling it to infect human cells. This scenario seems to fit other recent outbreaks of coronavirus-caused disease in humans, such as SARS, which arose from cat-like civets; and Middle East respiratory syndrome (MERS), which arose from camels.

The second scenario is that the new coronavirus crossed from animals into humans before it became capable of causing human disease. Then, as a result of gradual evolutionary changes over years or perhaps decades, the virus eventually gained the ability to spread from human-to-human and cause serious, often life-threatening disease.

Either way, this study leaves little room to refute a natural origin for COVID-19. And that’s a good thing because it helps us keep focused on what really matters: observing good hygiene, practicing social distancing, and supporting the efforts of all the dedicated health-care professionals and researchers who are working so hard to address this major public health challenge.

Finally, next time you come across something about COVID-19 online that disturbs or puzzles you, I suggest going to FEMA’s new Coronavirus Rumor Control web site. It may not have all the answers to your questions, but it’s definitely a step in the right direction in helping to distinguish rumors from facts.

[1] The proximal origin of SARS-CoV-2. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. Nat Med, 17 March 2020. [Epub ahead of publication]


Coronavirus (COVID-19) (NIH)

COVID-19, MERS & SARS (National Institute of Allergy and Infectious Diseases/NIH)

Andersen Lab (Scripps Research Institute, La Jolla, CA)

Robert Garry (Tulane University School of Medicine, New Orleans)

Coronavirus Rumor Control (FEMA)

NIH Support: National Institute of Allergy and Infectious Diseases; National Human Genome Research Institute


  • Wagner says:

    In their paper under #1 – “Mutations in the receptor-binding domain of SARS-CoV-2” – last paragraph, last 2 sentences. Thus, the high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is MOST LIKELY THE RESULT OF natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is STRONG EVIDENCE that SARS-CoV-2 is not the product of purposeful manipulation.

    Huh? How can you use “most likely the result of” and then “strong evidence” in the same paragraph? If you have to say – most likely the result of – then its not proven yet.

    I felt this paper did anything but “prove” it wasn’t genetically engineered. More like a paper to refer to when trying to prove a point. Like on Facebook. Refer to this published article as my reference of stated fact.

    And as matter of fact, this paper has been used as such in several articles so far…

    • John Pepper says:

      I appreciate seeing reasoned discussion of the actual evidence here, instead of authoritarian assertions that some ideas must not be considered or discussed. It would help even more to address the one piece of evidence that probably gave rise to the bio-weapon idea: Is SARS-CoV-2 in fact a recombinant virus containing sequence last seen in HIV? If so, has natural recombination between such phylogenetically distant viruses been seen before?

    • Caleb says:

      It’s problematic that the general public has such a limited understanding of the scientific method as to think that “Proving” is the basis of Science, when the objective is to accumulate strong evidence in a replicable experiment such that other scientists can further substantiate or refute the claim with additional evidence. If the authors of the paper were to claim supreme certainty beyond a shadow of a doubt, they would not be scientists, but preachers.

      That’s a two-edged sword, of course. We frequently reference science as natural law, when it’s really an evolving understanding of our experiences, and “Science” as an institution is a vaguely governed collection of individuals operating with different directives. We often fall into the mistake of citing sources as if they are carved in stone in order to win facebook debates, but by its nature science is wrong most of the time, and that’s how we grow to better understand what is right.

      So, yes, this paper does not “Prove” that COVID-19 is naturally originating, but it also doesn’t claim to.

      From the conclusion, “Although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here. However, since we observed all notable SARS-CoV-2 features, including the optimized RBD and polybasic cleavage site, in related coronaviruses in nature, we do not believe that any type of laboratory-based scenario is plausible.

      More scientific data could swing the balance of evidence to favor one hypothesis over another. Obtaining related viral sequences from animal sources would be the most definitive way of revealing viral origins.”

      Note those last two sentences– a call to action about further research, creating stronger evidence one way or the other, in order to better determine the origins. All we can do is build a case by gathering evidence, gaining a better understanding of the most plausible scenarios, and determining what steps we can take going forward to better prepare and protect ourselves.

  • Bill Hutchins says:

    So you are 100% sure that it was not designed in a lab because it resembles something else? I can imagine that virus design involves genetic engineering. But there are also other methods to steer natural selection, aren’t there?
    The state of the art in virus design is at least not such that a massive financial market move could be designed, with changes for the travel industry, oil prices, pension funds, culture even, what else. That is the work of wind makers. Cut out the news on animated “markets” and the verb “surge” at all and not 1/10th of USD 2 trillion would flow through Wall Street. 50% of investment had become “passive” so active traders could only benefit from turmoil.
    It’s interesting that you are dipping your toe into the “media.”
    A research director for RKI in Germany said in an interview that he expects the national statistical death rate to be in the same range as a normal year. So, what the media and all the comment bots on internet make of it, should be taken as sales/advertising/engagement messages anyway.

    Which doesn’t take away: Social distancing is currently advised! Not a vaccine but effective!! Stay home if you are sick or have a cold, fever or cough. Once people start infecting less than one other individual the epidemic slows.

    • zheng says:

      In the same way, can we say that the current global lockdown and distancing situation is purely a “natural” event of evolution itself without any human engineering and interference?

    • Charlie says:

      I swear I had this when working in Panama about 5 years ago. Fever and dry cough and difficulty breathing. Worked through it. Thought I was going to cough up blood at any moment, slight pain in liver area also. Lasted about 10 days.

  • Richard says:

    Thank you for this info.
    Might I suggest that we use the more accurate term adaptation instead of evolution. The virus remains a Corona Virus; It is not busy changing into a Spirochete.

  • Luke Dyson says:

    I don’t see how that paper can conclusively show the new sequence wasn’t derived from a CRISPR-cas9 method. The article and research don’t show evidence that researchers have tested the source mutation, simply a sample from one of the earlier confirmed cases. Mutations could have occurred at any time, beyond the first host, with the human genome.
    Any new research would try a different bases than previously existed, that’s the entire nature of new research. Although I don’t believe there was any malice.
    It appears to me that someone was attempting to create a cure(?) for the SARS and used a COVID delivery system. I’m guessing they were starting with select portion of the population with genome structure, as evident that the virus doesn’t have a significant impact on children.
    About the only conspiracy I could conjure, is that someone tried to skip ethical human trial and bypass in a purposeful release to test. But the virus traveled more than initially expected.
    One good thing I do think that could come from all this is the exceptional level of tracking of the virus transmission. This could be used in future research.

  • Matt says:

    So the fact that the outbreak occurred in Wuhan in the very same town that has one of China’s foremost institute of virology, the wuhan institute of virology is a meaningless coincidence? There are 400 cities in China not counting towns less than 10k population. So the official word is some Chinese ate some exotic animal and never mind it occurred at the steps of a virology institute. Come on now.

    • Jack says:

      So who ever created this went the entire distance to plan and create a brand new virus, to forget to put it further enough away from their Lab. Come on now

  • Daniel Gagnon says:

    Has anyone ever thought of another means for transmission of the coronavirus could be from having an infected smoker blowing out those tiny smoke particles which are first inhaled into their lungs and then expelled out through the mucus membrane into the air. The tiny smoke particles could have virus material attached to them which then floats in the air for all to breath into their unsuspecting lungs and voila they are now infected. Has any research been done on this possible theory?

  • Kevin says:

    You are too simple to understand what CCP can do. They’ve already started modifying human gnome, harvesting organs, etc.
    Time to wake up.

    • HVirdee says:

      The Military Games held in Wuhan Oct 2019, Iran being the second country to be majorly affected by Covid-19 (conveniently), US adding tariffs to Chinese made goods, China reciprocating showing dominance as a superpower, threatening the western powers, and Israel…all points back to one country.

      • Tanya Morgan says:

        More likely Chinese government are in close contact with Iran and that’s why so many high powered officials in Iran were affected. Which ideologies are totalitarian, ruthless and seeking to consolidate their power?

  • Hanzhen says:

    While I agree the 2 points in the paper here strongly suggest a natural origin of the coronavirus that causes COVID-19, they do not “prove” it. But it may be about the best scientists can do to refute the “non-natural original” theory. After all, it is impossible to directly observe (and unreasonable to expect) the moment virus jumped from bats or pangolins to human, given the number of potential hosts (billions of bats?) and number of virus replications (trillions?) that might have happened before the virus succeeded in infecting human effectively. As far as I know, we don’t have “proof” that SARS or MERS jumped from bat to human via intermediate hosts either?

  • John T. says:

    Dear Dr. Collins, I am intrigued by the above mention of a bat virus to human virus conversion time line that could be decades long. Approximately 7 1/2 years ago my 23 year old son and I (I was age 54),spent Sat. 9/8/2012 eradicating a small bat colony from under our cabin’s front porch roof. Because we were familiar with Hantavirus from mice, we took similar precautions with the “flying mouse” clean-up of accumulated bat feces and urine stains. Full eye goggles, N-95 nose and mouth masks, gloves, but just work shirts, pants and painters hats. About 15 adult bats departed the scene as we sprayed down the nesting area with a bleach/water solution (again, Hantavirus technique). Our goggles fogged up and were soon set aside so we could see what we were doing. We used the pressurized spray tanks on our ATV to wash out the area. We vastly underestimated the quantity of feces and urine. I told my son to step off the porch so as not to partake in the bat crap rainstorm I was creating. Our spray rinse technique turned this soupy mess into a veritable aerosol of a bat’s G.I.tract. There is no way we used enough bleach solution to neutralize the potential threat. A ways up the road are bat caverns that are visited by people from around the world. Bus loads of tourists.

    Nine days later I spent the day of 9/17/2012 clearing brush and cutting trees, feeling great, but by 8pm that night I was barely able to walk and was laying on the couch with chills and a 108F temp (taken with a real top grade oral thermometer). I got through the night with 6x 500mg Tylenol. By 10am the next day I walked into the way above average clinic and hospital in our Northern Rockies college town. By now, I’m walking so slow, yesterday is about to catch back up with me.

    My Dr. takes my temp, checks my CRP, it’s 150, checks me for strep and sepsis and says, “I don’t know what you have but you’re not leaving here with a 108F fever.” My Dr. has an infectious diseases and travel medicine specialist in his group, that’s good. In the hospital, three nurses walk in with the first dose of medicine, all three have to sign off that this is the correct med and correct dose. I ask, “Is this the A-bomb?” The nurse in command replies, with a way too straight face, “Not yet.” The rest of the day four doctors and an endless parade of phlebotomists work the problem.

    The next morning, I tell the phlebotomist, “Just take all my blood, then I’ll finally feel better.” He doesn’t even crack a smile, tough crowd. Maybe he heard that one before.

    The three nurses are back with a syringe in a lock box that requires all of their signatures. As the key is turned and the box clicks open, the head nurse looks me in the eye and says, “This – is – the – A-bomb.” Two days later I walk out of the hospital with no symptoms, a mad craving for mashed potatoes and a 15-day Rx for… not so fast everyone, no need to create a run on that. 15 days out, my CRP is 0.5 and all tests come back negative, including Rickettsia, Rocky Mountain Spotted Fever, Hantavirus, Anaplasma. My discharge nurse took a red felt tip pen and wrote FOUO on my documents. “Well, I learned a new acronym” I said, …”and you met your annual insurance deductible,” my wife said. From time to time I drop off Bat/Human disease magazine articles to my doctor who passes them on to the infectious diseases specialist. I sure think about those bats and that FOUO a lot lately.

    Is it possible I might have had an early run-in with the COVID-19 ? (or an early strain of it?)
    Might I be immune to the current strain?
    Would it be at all worthwhile to be check for immunity ?
    If I was immune, would my blood plasma be of any value in the current fight?

  • Bridget Johnsen says:

    As a vet and conservationist, I recommend publishing widely that the pangolin cannot be excluded as a suspect, so that all poachers finally get terrorised into leaving them where they belong…… in the wild and not on human plates!!

  • Dan Laks says:

    This referenced study assumes the use of a viral backbone which is not necessary if it is man made using a gene synthesizer such as the BioXP 3200. Thus, the conclusions of the cited study are not conclusive or even compelling.

  • zyl says:

    The Chinese have co-lived with and eaten bat/pangolin over thousands of years without any SARS-2 corona-virus problem. Why and how, then, suddenly starting in 2019, it becomes a huge health/disease problem? Using NIH-BLAST, one can see that both SARS-2 and Chinese human-ACE2 got some man-made or more likely lab-made elements. DURC (Dual Use Research Concerns). Keep this mind: in 9-11, civilian airplanes could be used as terrorist attack weapon. The same re bio-technology. In PRC, bio-tech management is badly out of control over the years, i.e., anything can happen there. —-gene-edited babies were already born in China, what else would be impossible?

  • IBS365 says:

    Thanks for this interesting analysis. Hope God will help us survive and that the world will come back to normal again.

  • cw says:

    Anderson et al. appear to be unaware of this (now worrisome) paper and the related chimeric research done in Wuhan:

    Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like
    Coronavirus of Bat Origin. Ren et al.JOURNAL OF VIROLOGY, Feb. 2008, p. 1899–1907 Vol. 82, No. 4

    The coincidence argument seems less well supported given what they were doing.

  • Michelie says:

    The COVID-19 epidemic is similar to the first outbreak of the Acquired Immune Deficiency Syndrome, not really knew what the transmission was. Perhaps we really don’t know if this is a flu or a type of parasite such as ticks.

  • meryl nass, MD says:

    Nature Medicine ran the 3 page article referred to by Collins that claimed to explain why the novel coronavirus is not a lab construct. USA Today wrote a summary piece explaining it:

    “If someone were seeking to engineer a new coronavirus as a pathogen, they would have constructed it from the backbone of a virus known to cause illness,” the report said. “But the scientists found that the SARS-CoV-2 backbone differed substantially from those of already known coronaviruses and mostly resembled related viruses found in bats and pangolins.”—USAT

    Yet it turns out to be a specious argument, relying on the fact that the novel coronavirus backbone sequence was not already known in the open virology literature.

    1. While starting from a known RNA sequence is one easy way to create a pathogen, it is certainly not necessary to do so.
    2. Nor is it likely that biodefense/biowarfare programs share knowledge of all their creations. They never have before.  
    3. Finally, it is relatively easy to detect the human hand when a chimera of known virulence factors is strung together.
    4. And because plausible deniability is a critical component of a bioweapons attack, I doubt that a chimera using known sequences is the path that would have been followed by a modern biowarrior.

    I will briefly mention some of the old techniques for creating bioweapons, none of which require that a known, published RNA backbone would be required to build a novel, virulent coronavirus:

    1.  China has unique bats.  So do other countries.  Unique bats likely harbor unique viruses.  Bits of these viruses can be strung together, while no outside parties are aware that these particular RNA threads exist in nature.

    2.  You take an already virulent RNA virus, subject it to high rates of mutation via chemical or radiological exposure, and test the viruses that survive for the acquisition of new virulence characteristics.

    3.  You simply passage the virus through tens, hundreds or thousands of lab animals or cell cultures and test the results for acquisition of new virulence characteristics.

    4. You mix different viruses together with different virulence characteristics, allow them to grow together, and seek recombinants that have obtained the desired new mix of virulence factors.

    All these possibilities result in viruses that are hard to pin on lab production. I dare the Nature Medicine scientists to dismiss these scenarios.

    Still, I doubt that any national program would deliberately release this coronavirus onto the people of the earth, because it is so hard to control.  Historically, bio-weaponeers required their creations to be controlled at all costs. Unleashing african swine fever, or dengue, on an island was associated with no spread beyond the island.

    So why do we have this epidemic (or epizootic, if it indeed travelled from animals to humans), now?

  • gosafeseal says:

    While I agree the 2 points in the paper here strongly suggest a natural origin of the coronavirus that causes COVID-19, they do not “prove” it. But it may be about the best scientists can do to refute the “non-natural original” theory. After all, it is impossible to directly observe the moment virus jumped from bats or pangolins to human, given the number of potential hosts and number of virus replications.

  • Jean Luce says:

    Does the c in CRP stand for corona?

    • Janaki Kuruppu says:

      CRP = C reactive protein
      this is a protein that is elevated in the blood when there is generalized inflammation.

  • P.S. says:

    Thanks for such an informative post!
    There are some Conspiracy theory flying in the air that COVID-19 is men-made weapon but it seems to me a ridiculous claim. Now it’s very much clear to me.

  • sarastro92 says:

    By serial infection of an animal model that closely resembles a human ACE-2 receptor a lethal, highly transmissible virus can be created that looks “natural”. In reality, the process is a “Guided Natural Selection”.

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