An interview with the German scientist who found 2017 research in SARS-CoV-2
Andreas Lisewski presentation for Christian Drosten and a WHO committee
Andreas Lisewski is a computational biologist at Constructor University in northern Germany. In 2024, he published a BMC paper that found a 2017 “precise molecular blueprint for SARS-CoV-2.” Ralph Baric of UNC referenced that 2017 research in his 2019 furin cleavage site paper.
In February 2025, Lisewski’s findings were presented to Christian Drosten (Baric of Germany) and the WHO’s Scientific Advisory Group for the Origins of Novel Pathogens (SAGO). The SAGO committee is investigating the origins of COVID-19, and the report on this data has yet to be published. However, this presentation, featuring Drosten’s name, has stirred the lab leak debate.
https://zenodo.org/records/15380908
The 2025 SAGO presentation was based on Lisewski’s 2024 paper titled: Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus
https://bmcgenomdata.biomedcentral.com/articles/10.1186/s12863-024-01290-2
Here, we report comprehensive sequence data to demonstrate that among spike proteins of genus Betacoronavirus and outside of the SARS-CoV-2 clade, a fully analogous S1/S2 domain was found in only one other virus: the artificial MERS infectious clone MERS-MA30, described already in 2017, which was rationally selected from serial passage in genetically humanized mice. As the evolutionarily closest betacoronaviruses outside of the SARS-CoV-2 clade lack all its three functional motifs, these data extend—beyond natural evolution and zoonosis—the current view on SARS-CoV-2 pre-pandemic origins by presenting the analogous S1/S2 MERS-MA30 sequence domain as a precise molecular blueprint for SARS-CoV-2.
In 2017, Baric’s University of Iowa colleague, Stanley Perlman, published PRRVRSV. Baric referenced that 2017 sequence PRRVRSV (yellow arrow) in his 2019 furin cleavage site (FCS) paper on MERS. SARS2 used PRRARSV and is the only SARS-like virus with an FCS. The FCS acts as a molecular scissor, allowing the virus to enter mammalian cells and enabling onward transmission.
Lisewski’s February 2025 presentation hypothesized that the SARS2 FCS was inserted into a RaTG13(-like) backbone, serving as a precise molecular blueprint (design target). Therefore, a natural origin of SARS2 is inconsistent with evolutionary evidence.
Baric’s UNC colleagues also published RRARSVAS, found in SARS2, in a 2018 ENaC paper. More importantly, this showed that Baric possessed the closest progenitors to SARS2, RaTG13 and BANAL-52, in 2018.
The 2017 MERS-MA30 molecular clone that Lisewski found has a pat7 (molecular “address label”) pattern of 7 amino acids. The first is always proline (P), explaining the PRRAR furin cleavage site. Natural origin scientists claimed no one would insert a proline. Before Lisewski’s paper was published, Baric testified:
Why would anybody engineer that and do it that way, putting in an extra residue which is a proline, which puts kinks in proteins, it usually screws things up. And ultimately, that proline changed within a few, within one or two variants.
Awkward, because Baric referenced that MERS-MA30 proline in 2019. Unlike SARS1, MERS has a furin cleavage site. Since SARS is on the “select agent list,” Baric often used MERS as a workaround. Baric referred to it as the “s-word” in this 2013 meeting organized by Fauci:
In the 2018 DARPA Defuse bid, Baric proposed inserting a furin cleavage site in novel coronaviruses and testing them on Chinese bats in Wuhan. Christian Drosten said of the Defuse bid, “It was also revealed that there were plans to insert furin cleavage sites, but this was to be done in an American [UNC] laboratory, and the project was not funded.” Well, Fauci funded it, and that’s why Baric was referencing furin cleavage sites.
For more on Andreas Lisewski, read our 2024 interview (above) or listen to his German interview. Below is a follow-up interview from May 2025, after Lisewski’s research was presented to German virologist Christian Drosten and the WHO SAGO committee. The indented vertical green lines represent Lisewski’s answers to my questions. Any typos or errors are mine:
Your preprint was withdrawn without your input in December 2022. In December 2024, BMC published your revised findings of furin cleavage site research from 2017, found in SARS2. Since January 2025, Christian Drosten has engaged with your MERS-MA30 research, which led to a SAGO presentation and further results. Does he support your theory?
Yes, during our extended scientific debate between January and March 2025, Dr. Drosten was open toward my evidence and also expressed support. But like any serious scientist, while open to substantial and credible positive evidence, Drosten also pointed out weaker points and limitations (see observations 4 & 5 below).
Drosten was supportive before the SAGO meeting, for example, by stating that my hypothesis would explain the suboptimal FCS in SARS-CoV-2. He also continued to be engaged after the presentation by outlining experimental plans to investigate further implications of my hypothesis at his own lab and through sequence data investigations on my end.
Was this your presentation to Drosten, or Drosten's presentation of your research to SAGO?
It was my data and presentation material, personally provided to him, that he then “completely” presented to SAGO on 18 February 2025.
The meeting was organized as a “special meeting” at Drosten’s initiative solely to discuss my evidence.
Can we watch a video of the exchange, or can you summarize it?
No, SAGO meetings are not public.
In observation 2, you hypothesized the intentional insertion of the SARS2 furin cleavage site (with pat7 NLS) into RaTG13’s spike since its RdRp was error-prone, allowing for directed in vitro evolution. Was this because the SARS2 RdRP was also error-prone or low fidelity?
There has been criticism that because RaTG13 CoV and SARS-CoV-2 share only around 96% genomic sequence identity, RaTG13 could not have been the latest evolutionary ancestor to SARS-CoV-2; also, for any suggested synthetic origin, this divergence would exclude RaTG13 as a candidate for a backbone SARSr-CoV and before any insertion of FCS, because of experimental impracticality through serial passaging (too many passages/too long time required to achieve the 4% observed
divergence).But SARS-CoV-2 replication machinery, being >99% identical in sequence to RaTG13, has a 3-4 orders of magnitude lower base substitution fidelity than other reported coronaviruses (i.e., an extremely high nucleotide substitution rate among CoV), making it probably a unique candidate for "fast-forward" directed evolution in the laboratory. In addition, fidelity can also be controlled with additional genomic factors (such as nsp14).
Observations 4 and 5 in the presentation are your positive responses to Drosten's original criticism: (1) MERS pat7/FCS is not ancestral to Wuhan, and (2) uses different codons. Why do these two points now make a very compelling case?
Drosten's valid criticism in these two points was indeed that, for MERS-MA30/MA1.0 FCS to be considered as a design target, there should be a connection of the early 2020 SARS-CoV-2 sequences that identically display a MERS-MA30/MA1.0 pat7/FCS to ancestral (Wuhan “basal”, late December 2019) SARS-CoV-2 sequences, but this was not obvious; and that my BMC Genomic Data paper about MA30/MA1.0 pat7/FCS argued only at the amino acid level, while at the nucleic acid level, the MERS MA30/MA1.0 FCS and the SARS-CoV-2 FCS use different codons, and this divergent SARS-CoV-2 FCS codon usage was not explained.
In direct response to Drosten's criticism, I produced additional data that resulted in these supplementary observations 4 and 5, which (I) reconstructed a genetically detailed ancestral lineage, beginning with the 15 December 2019 collection date of the globally first and already D614G carrying spike sequence sample from the Milan region, Italy. This epidemiologically relevant lineage, after establishing the characteristic linkage disequilibrium of (C241T C3037T C14408T A23403G) by February 2020 and across continents (Europe and Asia), then quickly culminated in those highly specific amino acid reversal mutations at the critical FCS (A684V and A688P, in Saudi Arabia and in Iran during the onset of the pandemic). (II) proposed the rational and synthetic design of the SARS-CoV-2 S1/S2 FCS by means of the two concatenated type IIS restriction enzyme binding domains (FauI and MnlI), which essentially and intrinsically explain the codon usage along with its peculiarities (e.g., CGG-CGG).
For version 2 upload, why did you add, “At nucleotide level, two combined type IIS restriction enzyme recognition sites (FauI and MnlI) essentially encode the MERS-MA30/MA1.0 FCS target as seen in SARS-CoV-2, to which ancestral (15 December 2019) D614G lineage evolved through spike reversal mutations prior to the onset of the pandemic.”
This was to emphasize observations 4 and 5, which are the responses to Dr. Drosten’s main criticisms.
WA1 remains the best-known ancestral strain of SARS2 and predates Wuhan-Hu-1 and D614G. WA1 was isolated from an American traveller returning from Wuhan, but he did not visit the Wuhan wet market. The WA1 isolate does not infect humanized mice but transmits efficiently in Egyptian fruit bats. These Egyptian fruit bats (Rousettus aegyptiacus) were also used for in vivo coronavirus research, so do you have any input?
With the currently publicly available data, it cannot be inferred that WA1 is ancestral to the D614G lineage, as they are phylogenetically distinct lineages. On the contrary, by collection date, the Milan (Italy, Genbank MZ223393.1) isolate from 15 December 2019 is the first documented SARS-CoV-2 spike isolate globally, an isolate that already carries D614G (A23403G) and which was collected more than 2 weeks before any member of the WA1 lineage (including the earliest 30 Dec 2019 isolate Wuhan_IME-WH01). So, Wuhan probably was not the original source of SARS-CoV-2 introduction into the human population, and certainly not the earliest by collection date record. This observation argues against a singular, localized zoonosis event in Wuhan and may also independently support a non-natural origin hypothesis.
At this time, I cannot respond with anything directly relevant to your questions regarding infectivity in humanized mice vs fruit bats. However, remarkably, a German 2023 study has shown that SARS-CoV-2 FCS is a positive determinant of horizontal transmissibility, which would make a synthetic, non-natural origin of FCS even more concerning.
Stuart Neil has been critical of your paper since 2022 and is currently on Bluesky, trying to discredit it. Would you be able to respond?
Dr. Neil has repeated this same argument since 2023, but has been unable to correct his personal opinions despite accumulating scientific evidence against:
(I) Contrary to Dr. Neil's argument, no cell biology principle would absolutely prevent the spike protein from entering the host nucleus. NLS carrying proteins with equal transmembrane topology as SARS-CoV-2 spike do have mechanisms for nuclear pathways, e.g., fibroblast growth factor receptor 1 (FGFR1); as such, spike protein export might bifurcate at the ER-Golgi apparatus with an additional nuclear pathway that mimics or hijacks cellular FGFR1 signaling.
(II) One objection to Dr. Neil's criticism is that Sattar et al.'s 2023 paper on spike protein/RNA nuclear translocation is based on a meticulously developed experimental spike protein microscopy approach that was published between 2021 and 2023 in several specialist journals.
(III) Sattar et al.'s 2023 paper on spike protein/RNA nuclear translocation is not an isolated study. Since 2020, there has been mounting evidence of nuclear translocation (as briefly discussed in the BMC paper). After 2023, important parts of Sattar et al.'s findings have been independently verified.
(IV) While I agree with Dr. Neil that a recombinant pat7-negative variant would perhaps be a useful control, the burden is on him to show or to prove that no relevant amounts of spike protein (and RNA) enter the human nucleus.
(V) In any case, for the now hypothesised synthetic origin of SARS-CoV-2 spike pat7/FCS, such control would make no practical difference: the original MERS-MA30 pat7/FCS sequence pattern detected after passaging in humanized mice is a positive marker of virulence and disease. Therefore, any intentional use of it as a design target can be done with or without prior knowledge of the underlying cellular mechanisms (such as nuclear transport, etc.), as was already demonstrated with MA30/MA1.0 in 2017.
Did Dr Masfique Mehedi from the University of North Dakota (Sattar et al) contact you about his pat7 findings? Does he agree with your conclusions?
Yes
Biologist Sigrid Bratlie from Norway agrees with your conclusion. Does anyone else?
Yes
Anything else, and what is the next step on your lab leak brilliance?
Thank you.
It's obviously NOT a virus. It is a lab created bioweapon. Let's finally start calling it what it really is for a change.
Thanks Jim! If I understand properly:
- Some work by Drosten (2017) on MERS virus was reused by any SarsCov2 designer, for the FCS
- the strain in Italy would predate any so-called Wuhan strain.
Very interesting !
Best -