In fact, analysis of some early strains of SARS-CoV-2 shows that they may be more similar to bat coronaviruses than previously thought, based on evidence recovered from viral sequences deleted from NIH sequence archives.

  • During lab experimentation with the bat coronaviruses, it is possible that a novel virus was produced with greater similarity to SARS-CoV-2 than those reported in the NIH grant.

The researchers stated in the grant that they developed an in vivo model, that is, mice genetically engineered to carry human angiotensin-converting enzyme 2 (hACE-2), the receptor for SARS-CoV-1 and SARS-CoV-2.

The research group also reported that they were successful in generating new SARS-like coronaviruses. They did this by splicing the RNA sequences of the novel spike proteins they discovered into the viral ‘backbone’ of known lab strains. This kind of novel virus is called a chimera because it consists of genetic elements from different viruses.

In this way, the researchers created three chimeric viruses, each with a different spike protein, from bats.

  • Though the grant does not mention a virus similar enough to SARS-CoV-2 to be a direct progenitor, it is possible that other chimeric viruses were tested in this model, but were not reported in the grant. The researchers had access to troves of novel coronaviruses collected during fieldwork, including unreported bat viruses.

It is common for researchers to present some but not all data in interim grant reports. The research described in the grant established a platform that could have easily been used to study other chimeric viruses more closely related to SARS-CoV-2 than those mentioned in the grant.

There are indications of this within the grant documents. While results from infection of hACE-2 mice with three chimeric viruses were presented, the researchers wrote in the grant, “[w]e cannot anticipate exactly how many viruses we will find that are candidates for experimental models … and that we will identify approximately 20 viruses that will be used for mouse infection experiments.”

It is possible that the researchers generated a novel chimeric virus with more similarity to SARS-CoV-2 than those reported.

Experiments on human ACE-2 mice

The NIH grant describes important research on mice with human ACE-2 receptors.

The researchers infected the hACE-2 mice with the chimeric SARS-like bat coronaviruses to see how sick they would get, and whether they would shed infectious virus compared to the original viral strain.

They found that hACE-2 mice infected with some of the chimeric viruses lost more body weight and shed more virus in the lungs than those infected by the original viral strain at certain time points. This research resulted in chimeric viruses that gained infectious and pathogenic properties.

“We’ll infect them [hACE-2 mice] with cultured bat coronaviruses and determine which organs become infected and whether these mice are capable of shedding infectious virus”, the grant proposed. The grant aimed to study tissues of the chimeric virus-infected hACE-2 mice for virus replication.

The grant proposed testing different transmission routes in which the mice could be infected, comparing nasal infection versus other routes.

The grant outlines, “[W]e will perform in vivo infection experiments in humanized mice modified to carry human ACE2 … gene in the Wuhan Institute of Virology BSL-3 animal facility … [t]his work will provide information about viral pathogenicity, tissue tropism, transmission route, and infection symptom.”

An outstanding question is whether the chimeric viruses can be transmitted between the hACE-2 mice. Whether the scientists explicitly reported on this is not the question, but rather, was a novel chimeric bat virus engineered that was also transmissible between hACE-2 mice?

While the grant does not discuss repeated passage of viruses in hACE-2 mice, the platform also sets up biosafety concerns about this possibility.

A weakness in the prominent ‘proximal origin’ paper?

Some scientists who have argued against a lab origin for SARS-CoV-2 contend that the virus has a signature of it being adapted in an animal host with an intact immune system, for which no such appropriate laboratory model has been described.

One of these arguments against a lab origin of SARS-CoV-2, advanced by scientist Kristian Andersen and colleagues, and published as an influential correspondence in Nature Medicine, was “[s]ubsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described.” [Emphasis ours.]

However, the grant shows this is not correct — the experimentation on the hACE-2 mice establishes such a model.

Infection of hACE-2 mice with the novel chimeric bat coronaviruses could have supported new viruses with sequence changes that make them better able to infect human cells. These could be more similar in sequence to SARS-CoV-2 than the original chimeric virus infecting strains.

The hACE-2 expressing mice could have enabled some human adaptation of the chimeric SARS-like bat coronaviruses in vivo, generating viruses with more similarity to SARS-CoV-2 than those reported to date.  This is another possible explanation for how NIH-funded research in China could have led to the COVID-19 pandemic.

The bottom line

In addition to searching for spillover events, the research outlined in the grant had the potential to generate a spillover event.

This could have occurred as an accidental infection during fieldwork and laboratory handling of bat SARSr-CoVs, during containment or storage of them, during the laboratory engineering of novel chimeric bat coronaviruses or, after these novel viruses were used to infect hACE-2 mice, leading to a more infectious, transmissible and/or pathogenic virus that was a precursor to SARS-CoV-2.

The possibility of a lab leak or lab-acquired infection with any of these novel coronaviruses during lab experimentation raises serious biosafety concerns.

Though the bat coronavirus grant project has concluded, it is entirely possible that other studies using this platform were performed or are now being performed, including those related to a viral transmission. It is noteworthy that it took civil litigation to bring these grant documents to light, even though the research itself was paid for by U.S. taxpayers.

It is also noteworthy that EcoHealth Alliance has received nearly $40 million in multiple grants from the Department of Defense, and DOD grant data is often considered classified and withheld from the public.

And though the 5-year bat coronavirus research grant was only renewed for one additional year, a $7.5 million NIH grant, titled “Understanding Risk of Zoonotic Virus Emergence in EID Hotspots of Southeast Asia,” was awarded to EHA in 2020 to expand on the platforms established in the 2014 grant.

This newer grant, with Daszak again as principal investigator, was also made public in early September by the Intercept. The new grant is a consortium grant that adds more collaborators and lab sites where the research will be performed, including a BSL-4 facility in Boston. Funding is approved for the budget cycle of June 17, 2020, through May 31, 2025.

The bottom line is this: It is unclear whether the work performed under the 2014 bat coronavirus NIH grant played a role in the COVID-19 pandemic. But the EcoHealth Alliance and WIV collection and storage of SARS-related bat coronaviruses, and the creation and use of chimeric novel bat coronaviruses with human ACE-2 expressing mouse platforms, could have sparked the pandemic.

Congress should launch an investigation into U.S. government funding of this type of risky research as part of a full and thorough investigation of the origins of the pandemic.

U.S. Right to Know believes transparency in science is essential to the protection of public health, including preventing future pandemics.

Originally published by U.S. Right to Know.