New Study Finds SARS-CoV-2 Binds Best to Humans — Not Bats or Pangolins
Scientists using computer modeling to study SARS-CoV-2, the virus that caused the COVID-19 pandemic, have discovered the virus is most ideally adapted to infect human cells — rather than bat or pangolin cells, again raising questions of its origin.
In a paper published in the Nature journal Scientific Reports, Australian scientists describe how they used high-performance computer modeling of the form of the SARS-CoV-2 virus at the beginning of the pandemic to predict its ability to infect humans and a range of 12 domestic and exotic animals.
“Humans showed the strongest spike binding, consistent with the high susceptibility to the virus, but very surprising if an animal was the initial source of the infection in humans.” Professor David Winkler, La Trobe University
Their work aimed to help identify any intermediate animal vector that may have played a role in transmitting a bat virus to humans, and to understand any risk posed by the susceptibilities of companion animals such as cats and dogs, and commercial animals like cows, sheep, pigs, and horses.
The scientists, from Flinders University and La Trobe University, used genomic data from the 12 animal species to painstakingly build computer models of the key ACE2 protein receptors for each species. These models were then used to calculate the strength of binding of the SARS-CoV-2 spike protein to each species’ ACE2 receptor.
Human Cells Bind SARS-CoV-2 Better Than Bat or Pangolin Cells
Surprisingly, the results showed that SARS-CoV-2 bound to ACE2 on human cells more tightly than any of the tested animal species, including bats and pangolins. If one of the animal species tested was the origin, it would normally be expected to show the highest binding to the virus.
“Humans showed the strongest spike binding, consistent with the high susceptibility to the virus, but very surprising if an animal was the initial source of the infection in humans,” says La Trobe University Professor David Winkler.
The findings, originally released on the ArXiv preprint server, have now been peer-reviewed and published in Scientific Reports (Springer Nature).
Challenging Direct Bat-to-Human Transmission Theory
“The computer modeling found the virus’s ability to bind to the bat ACE2 protein was poor relative to its ability to bind human cells. This argues against the virus being transmitted directly from bats to humans. Hence, if the virus has a natural source, it could only have come to humans via an intermediary species which has yet to be found,” says Flinders affiliated Professor Nikolai Petrovsky.
The team’s computer modeling shows the SARS-CoV-2 virus also bound relatively strongly to ACE2 from pangolins, a rare exotic ant-eater found in some parts of South-East Asia with occasional instances of use as food or traditional medicines. Professor Winkler says pangolins showed the highest spike binding energy of all the animals the study looked at — significantly higher than bats, monkeys, and snakes.
“While it was incorrectly suggested early in the pandemic by some scientists that they had found SARS-CoV-2 in pangolins, this was due to a misunderstanding and this claim was rapidly retracted as the pangolin coronavirus they described had less than 90% genetic similarity to SARS-CoV-2 and hence could not be its ancestor,” Professor Petrovsky says.
This study and others have shown, however, that the specific part of the pangolin coronavirus spike protein that binds ACE2 was almost identical to that of the SARS-CoV-2 spike protein.
Convergent Evolution, Recombination, or Engineering?
“This sharing of the almost identical spike protein almost certainly explains why SARS-CoV-2 binds so well to pangolin ACE2. Pangolin and SARS-CoV-2 spike proteins may have evolved similarities through a process of convergent evolution, genetic recombination between viruses, or through genetic engineering, with no current way to distinguish between these possibilities,” Professor Petrovsky says.
“Overall, putting aside the intriguing pangolin ACE2 results, our study showed that the COVID-19 virus was very well adapted to infect humans.”
“We also deduced that some domesticated animals like cats, dogs, and cows are likely to be susceptible to SARS-CoV-2 infection too,” Professor Winkler adds.
The extremely important and open question of how the virus came to infect humans has two main explanations currently. The virus may have passed to humans from bats through an intermediary animal yet to be found (zoonotic origin), but it cannot yet be excluded that it was released accidentally from a virology lab. A thorough scientific, evidence-based investigation is needed to determine which of these explanations is correct.
How and where the SARS-CoV-2 virus adapted to become such an effective human pathogen remains a mystery, the researchers conclude, adding that finding the origins of the disease will help efforts to protect humanity against future coronavirus pandemics.
Reference: “In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin” by Sakshi Piplani, Puneet Kumar Singh, David A. Winkler and Nikolai Petrovsky, 24 June 2021, Scientific Reports.
DOI: 10.1038/s41598-021-92388-5
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23 Comments
And in the “land of the free” no one was allowed to discuss this on Facebook, twitter, etc. for the last 16 months, even though there was plenty of evidence that a Wuhan lab leak was a likely scenario and plenty of evidence that the wet market theory was unlikely. Reporters refused to look into it, and all the “fact checkers” insisted it was a debunked conspiracy theory.
All because it would have benefited President Trump a little (not a lot, because no one was accusing him of being the source.) No, they would rather lie to protect the communist government of China, rather than help the American president a smidge.
Worst of all is the scientists, who should be above politics, who wouldn’t investigate or call things out sooner. The government scientists should especially be apolitical, and not use their official capacity to benefit candidates, but all government employees routinely favor the Democrats so that they can continue to ride the gravy train of an every expanding government at taxpayers’ expense.
Now after Trump has been out of office for months we’re finally beginning to be able to discus this, report it, and investigate it. How many millions of lives and billions of dollars could have been saved if everyone could have rationally looked at issues like this and potential COVID therapeutics all along.
Dude, anything comparing Trump to rational is funny. I see your point, about not following up on this earlier though, but if you remember, there was no EVIDENCE that the lab theory was more likely. This is the type of evidence that is needed before we can start holding China accountable for any negligence on their part. As for the “millions of lives and billions of dollars” BS, don’t make me laugh. If Trump had definitive proof it came from China, he would have taken us to war. He was itching for a reason to take down China and this would have given him at least some semblance of grass-roots support for it. Diplomacy was not in his vocabulary.
Regardless, I am in healthcare and I can tell you definitively that if infected people had been wearing masks earlier on, the transmission rate would have been significantly lower. THAT would have saved lives and dollars. But no, we had to politicize medicine and fight masks like they were shackles on our freedom.
BTW, notice in your last paragraph how we are NOW starting to be able to discuss this without politicizing it? You don’t see the correlation with Trump being out of office? No offense, but he lost the vote for a reason. The majority of people in this country saw through the QAnon BS and aren’t as rabidly right wing as you die-hard supporters are. Maybe now we can let medicine make medical recommendations regarding our health instead of politicians again.
Was there no evidence, or was the evidence mercilessly mocked by TV personalities until it wasn’t considered evidence anymore?
Man, you are part of the problem. Stop drinking the Kool-aid, don’t let your political beliefs corrupt the truth. See the facts as they are. You are allowing yourself to be manipulated by a corrupt political system with an agenda to maintain control. It is called brainwashing.
Can it with that nonsense. You & friends last year were accusing public figures of running a child abduction ring so that they could harvest adrenaline metabolites that everyone can produce by running in circles for 5 minutes. Then there was something about microchips in vaccines, and bunch of other psycho theories that were all fringed out with occasional murder threats and government overthrow. Nobody was going to have a conversation with you because your credibility was permanently destroyed with no path to redemption. You’re still not invited to the table.
Everybody knows that the virus came into being at the Wuhan wet market and if you don’t then you’re a racist that hates Vietnamese people. Despite Saint Fauci being the premier proponent of gain of function research, he has spoken and the media has determined that any other thought is blasphemy.
Millions of people are dead because our ex-president led his followers in the wrong direction, and they blindly followed. Knowing the origin of the virus has no bearing on how to defend against it. Those defenses were systematically destroyed by the ex-president and his supporters with disinformation. Engineered or not, the virus was real and masks work, two key points Trump and his followers continuously denied. Now the only people dying from the virus are the stupid unvaccinated ones, almost all of whom followed Trump straight into hell.
The former president was great at spreading all kinds of lies. If he is the genius he claims to be, he sorta had to know this means stuff with kernels of truth would also be stepped on. If he’s a ge it’s, he understood exactly that. So I don’t pity the x president.
Go back to the Florida swamp and suck a bat trumptards.
“Millions of people are dead because our ex-president led his followers in the wrong direction, and they blindly followed” says Brad Martin. Trump killed millions of Americans? It’s Trump’s fault that India is in a COVID crisis? No, this was a totally man-made virus from China. It’s Trump’s fault that Cuomo killed old ladies in nursing homes? Eat it China-loving libs.
Trump decided to disband the United States Pandemic Response Team.
Trump claimed many times that Coronavirus isn’t a threat, “It’s like 15 cases”
Trump turned it into a political issue and demanded that we stop testing because it was making him look bad
The pandemic was made worse by bad leadership. Trump is the definition of failure.
Don’t you guys have an insurrection to attend or something? As TRAITORS to the US, you have no room to talk anymore. American Citizens don’t care what TRAITORS think. Don’t like it? Move to Russia. They have EXACTLY the kind of government you want.
your an idiot, i can tell Trump has invaded your metal capacity to think strait, lol
Another sociopathic liberal who plays the fiddle as liberal run cities burn and descend into chaos as the crime and murder rates soar. Who are the real racists and traitors to our country? Look in the mirror. If you are not part of the solution YOU are the problem.
At this very moment in time, almost all COVID-19 deaths in the U.S. are in people who weren’t vaccinated which is an excellent demonstration of how effective the vaccine is. The deaths per day are now down to under 300. As any rational person can see from these number, the death rate could be close to zero if everyone (Other than those suffer anaphylaxis or other issues) got the vaccine.
In what they call “breakthrough” infections, fully vaccinated people accounted for fewer than 1,200 of more than 853,000 COVID-19 hospitalizations. That’s about 0.1%. Around 150 of the more than 18,000 COVID-19 deaths in May 2021 were in fully vaccinated people. That translates to about 0.8%, or five deaths per day on average. GOP states and GOP areas now account for the vast majority of Covid-19 cases in America. You Trumpsters are killing yourselves and acting as the reservoir for this viscous disease in America. Y’all Please move to Russia – You will fit right in.
At this very moment in time, almost all COVID-19 deaths in the U.S. are in people who weren’t vaccinated which is an excellent demonstration of how effective the vaccine is. The deaths per day are now down to under 300. As any rational person can see from these number, the death rate could be close to zero if everyone (Other than those suffer anaphylaxis or other issues) got the vaccine.
In what they call “breakthrough” infections, fully vaccinated people accounted for fewer than 1,200 of more than 853,000 COVID-19 hospitalizations. That’s about 0.1%. Around 150 of the more than 18,000 COVID-19 deaths in May 2021 were in fully vaccinated people. That translates to about 0.8%, or five deaths per day on average. GOP states and GOP areas now account for the vast majority of Covid-19 cases in America. You Trumpsters are killing yourselves and acting as the reservoir for this viscous disease in America. Y’all Please move to Russia – You will fit right in.
The reason it was banned has as much to do with Trump’s behavior as the response to it. If over half the people respond a certain way to his behavior and he continues to behave in that manner, he is just as much of a problem as the response. I argue even more because he was supposed to be a leader. He lied and made stuff up often, so there was a political response. He blamed China and pretty much anybody for everything, just because he may be right this one time, he still was the boy who cried wolf with conspiracy theory after conspiracy theory. His leadership style failed miserably if over half the people thought something was false just because he said it was true. If you really believe there is an issue, say it in a way that people will listen. He was not capable of that.
A mystery? Really? It’s not. If people eat bats and make soup from the blood then it is no mystery. Especially dead one’s. If a animal is dead from “natural causes”, it’s dead for a reason. Don’t eat it or make blood soup from it. Common sense people! Makes no sense to me.
American leftists are in deep collusion with the CCP. Just think how the world would have suffered less if a massive roundup of the 1930’s Liberal contemporaries happened and they were hanged. Let’s not make the same mistake twice. Round them up.
No one is sure about the origin but I believed in human engineering/re-engineering of the virus from the very beginning. There are chances that this was a highly classified experiment to see the efficacy of such engineering. If that’s the case, there may be more lethal ones on the way, not necessarily as bioweapon but as a tool to reduce human population to slow environmental damage.
How stupid is Brad Martin ?
I have to say, Trump did say this was a manmade virus and that China did cause this, he may be right and everyone else might be wrong. But also prior to that he stated the whole pandemic was made up by Democrats, or libs as some of you call them and there was no virus… then he said it was a witch hunt by “Dems”… then said it was “absolutely” under control, no problem here and it will be gone in the spring… then again said it would magically “Disappear” on it’s own after stating there were only a couple of people who had the virus and it was “almost” gone already… then said he “just believed” it was engineered, offering no proof to support his “idea”. As the saying goes, even a broken clock is right twice a day, that doesn’t mean the gears upstairs are turning correctly though. If you throw out a bunch of “theories” one of them is bound to be right statistically speaking, at some point in the future; finally Trump “Got one right”!
You state,
“It is noteworthy that the RBD common to both pangolin CoV and SARS-CoV-2 binds strongly to both pangolin and human ACE2, despite significant differences in these ACE2 molecules with only 63% of their binding site residues being common”
Should not the question be, does the Malayan pangolan RBD bind to RaTG13 ACE2, to facilitate recombination event where pangolan RBM is donated to the bat virus?
Recently, Kefang Liu, Xiaoqian Pan, and others have shown that RaTG13 RBD was unable to interact with Malayan ACE2.
“The RaTG13 RBD was capable of binding to human, monkey, rabbit, cat, fox, dog, raccoon dog, horse, pig, bovine, wild Bactrian camel, goat, sheep, and mouse ACE2, with equilibrium dissociation constant (KD) values of 0.5–7.14 mM, but were unable to interact with Malayan pangolin, civet, little brown bat, least horseshoe bat…”, in the article “ Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species”, by Kefang Liu, Xiaoqian Pan, and others, Cell 184, 3438–3451, June 24, 2021
If other studies verify this, then the question becomes the reverse scenario. Does Malaysian pangolin RBD bind RaTG13-related ACE2 effectively? For Malaysian pangolan coronavirus to donate its RBM to a RaTG13-related bat, this binding would have had to occurred. Ruling out concurrent evolution or some other unnatural process in bats and pangolans, as the ones below,
“These results suggest that the SARSr-CoV spike protein and Rhinolophus sinicus ACE2 may have ‘coevolved’ over time and experienced selection pressure from each other, triggering the evolutionary arms race dynamics. It further proves that Rhinolophus sinicus is the natural host of SARSrelated-CoVs…In a ‘host-virus arms race situation’, the genes involved tend to display dN/dS ratios (nonsynymous/synonymous mutation) greater than 1 (positive selection), specifically in the codons involved in the interaction interface between the virus and its host, with minimal effect on their physical function…….Similar ‘rapid adaptation’ for SARS-CoV occurred during the SARS outbreak in 2002-2003 …… bat SARSrelated-CoVs may decrease their virulence to fit both the host and themselves.” in the article, “Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes”, by Hua Guoa, Bing-Jie Hua, Xing-Lou Yanga, Lei-Ping Zenga, Bei Lia, Song-Ying Ouyang, Zheng-Li Shia, https://doi.org/10.1101/2020.05.13.093658
Setting aside this Zhengli doctrine of coevolution and ‘rapid adaptation’, the question remains, does the Malaysian pangolin RBD bind RaTG13-related ACE2 effectively, to help facilitate pangolin coronavirus entry into RaTG13 related bat? To set the stage for a recombination event in the bat 50 years ago. And questions of bat coronavirus persistence in that possible reservoir.
Did Malaysian pangolan coronavirus ever exist in those pangolans as reservoir, or as disease. This question has been answered by many as, ‘disease’. Because the pangolan coronavirus seemingly has the same pathogenicity in pangolans, as Covid-19 in humans.
And the Malayan pangolin coronavirus is being reported as 90% identity with Covid-19, thus being put into the same lineage as Covid-19. Figure 1 in article, “The evolutionary history of ACE2 usage within the coronavirus 1 subgenus Sarbecovirus”, Wells, H.L, Letko, M, Vincent Munster, and others, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928622/pdf/veab007.pdf
One last observation. On Jan 22, 2020, the Guangdong Institute filed sequences SRR10168377 and SRR10168378 viromes for dead Malaysian pangolins lung07 and lung08 with the NCBI. https://www.ncbi.nlm.nih.gov/sra/?term=SRR10168377%20 and https://www.ncbi.nlm.nih.gov/sra/?term=SRR10168378 to see the filing date.
On the very next day, January 23, 2020 ‘tortube’ (Matthew Wong) posted on the Internet, that the RBD (receptor bind domain) for dead Malaysian pangolins was highly similar to RBD for Covid-19, using sequences SRR10168377 and SRR10168378 to reconstruct Malaysian pangolin coronavirus genome. https://virological.org/t/ncov-2019-spike-protein-receptor-binding-domain-shares-high-amino-acid-identity-with-a-coronavirus-recovered-from-a-pangolin-viral-metagenomic-dataset/362
So ‘rapid adaptation’ does occur.
The February 6, 2020 letter from University of North Carolina to the University of Minnesota regarding RFP PA-19-056, “Cell entry, Cross-Species Transmission and Pathogenesis of Novel Coronavirus from Wuhan”, to the National Institute of Health, shows Baric’s desire to study pangolin coronaviruses at that early date. Fang Li’s e-mails at https://usrtk.org/wp-content/uploads/2021/07/Fang-Li-emails.pdf page 1034 Source to be questioned on these issues.
Le virus de la gripe covid 19 a été crée par le laboratoir Pasteur chez les français