The Only Amino-Acid Difference Between SARS-CoV-2 and Its Closest Ancestor's Human-Binding Motif Was Mutated in Pre-Pandemic Strains in 2007
Q498 was also downplayed in 2020 by Ralph Baric and Nature's 'Proximal Origin.'
There is only one amino acid residue within the receptor-binding motif (RBM) of the SARS-CoV-2 spike protein, responsible for fastening the pathogen to human cells, that is different from the RBM of the pre-pandemic coronavirus strain BANAL-52.
A single residue—Q498—is responsible for upgrading pre-pandemic strain RBMs into a version that binds human ACE2 receptors far more tightly.
The entire spike protein, including the RBM, of BANAL-52—curiously discovered immediately following the pandemic and used to justify SARS-CoV-2’s “natural” origin—differs from the full SARS-CoV-2 spike by only 20 residues.
But the Q498 RBM residue stands out for its upgraded effectiveness at binding to human cells.
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According to a 2021 ACS Nano computational mutagenesis study, Q498 is one of the SARS-CoV-2 spike protein’s principal binding hot spots.
The residue is explicitly described as “a viral protein/receptor binding hot spot” that “play[s] a major role in shaping the relevant region of the protein/protein binding interface.”
Q498 simultaneously anchors ACE2 at two of its most important contact points—“Q498 has anchored ACE2 D38 and K353 in two topical intermolecular HBs (2.92 Å and 2.87 Å)”—while also stabilizing the spike internally through additional hydrogen bonds to “N501 (3.02 Å) and Y449 (3.04 Å).”
This makes Q498 the most interaction-dense residue in the ACE2-binding region, the only one documented to form a multi-node network linking ACE2’s D38/K353 hotspot to internal RBD residues Y449 and N501 at the same time.
When Q498 is mutated to no longer possess Q (glutamine), the ACS Nano study reports a major loss of binding free energy, with W498 (tryptophan) showing a destabilization of ΔΔG = −4.18 ± 0.11 kcal/mol—one of the largest affinity collapses recorded for any single RBD residue.
Pre-Pandemic Mutation of Q498 Equivalent in Urbani Strain Y484
One pre-pandemic equivalent to SARS-CoV-2’s Q498 is the Urbani strain’s Y484.
The equivalence is confirmed in a chart produced by University of North Carolina Chapel Hill’s Ralph Baric and colleagues in an August 2020 Nature publication.
Baric’s own team deliberately mutated Urbani residue Y484 in human cells, as reported in a July 2007 PNAS study.
That means Baric’s group directly altered the pre-pandemic homolog of the single most important residue for SARS-CoV-2’s ability to bind human cells.
Baric reported that altering Urbani residue 484 changed how well antibodies could neutralize the virus, directly demonstrating that Baric’s lab understood the functional and immunological significance of this ACE2-contact position long before the appearance of SARS-CoV-2.
By engineering this mutation and demonstrating altered neutralization in human cells, Baric was performing reverse-genetics gain-of-function (GOF) research—genetically modifying a key receptor-binding residue to change the virus’s functional properties.
Baric knew how to mutate Q498-equivalent residues more than a decade before the COVID-19 pandemic.
Baric & ‘Proximal Origin’ Hide Q498 in Plain Sight
Just months into the pandemic, Baric published a March 2020 paper in Journal of Virology in which he identified spike protein residue Q498 as an “ACE-2-contacting residue.”
However, Baric failed in that paper to discuss Q498 anywhere outside the chart, hiding its significance in plain sight.
The journal Nature published ‘Proximal Origin’—relied on by the mainstream to argue for SARS-CoV-2’s “natural” origin—on the very same day Baric published his Journal of Virology paper.
Proximal Origin cited Baric’s Journal of Virology paper, and similarly excluded Q498 from its own list of critical ACE2 contacting residues.
And like Baric’s paper, Proximal Origin quietly placed Q498 inside a technical graphic at an inconspicuous location, while failing to discuss the residue outside the graphic.
Bottom Line
Taken together, the sequence match, the pre-pandemic mutagenesis work, and the post-pandemic binding data point to the same uncomfortable conclusion: the one RBM residue BANAL-52 lacks—Q498—is the very position laboratories were already manipulating and the very position that makes SARS-CoV-2 bind so effectively to human cells.
And contrary to the mainstream narrative, top COVID origins researchers believe the U.S. government had BANAL-52 in hand long before the pandemic began.
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I’m not a scientist. My head spins trying to understand all this highly technical stuff. Are you basically saying that this is definitive proof that the likes of Baric, Danzak/ Eco Health, Wuhan lab, Defense Dept etc made this C19 bug in a lab?
Was this his “No See Um” sequence by chance?