Andersen’s claim that a designer could not have predicted SARS-CoV-2’s high-affinity human-ACE2 RBD is weakened because structural analysis shows it recognises hACE2 more efficiently than SARS-CoV, chimera work shows bat spikes bind hACE2 with more plasticity than predicted, and WIV1/Rs3367 (which binds hACE2) already shares four of six critical RBD residues - so effective hACE2 binding was foreseeable/selectable in the lab.
Reasoning
Andersen et al. argued that because models built on the SARS-CoV RBD would not have predicted SARS-CoV-2’s binding solution, the RBD was unlikely to be designed. Segreto and Deigin counter that (1) Wan et al.’s structural analysis indicates SARS-CoV-2 recognises human ACE2 more efficiently than SARS-CoV; (2) gain-of-function chimera experiments demonstrated bat CoV spikes bind hACE2 with more plasticity than earlier predicted; and (3) the bat strain Rs3367/WIV1 - shown to bind hACE2 directly - already shares four of the six critical RBD residues with SARS-CoV-2, so a researcher could reasonably have expected a related RBD to bind hACE2. Consequently the ‘no one could have designed this’ premise does not hold, and rational design or lab selection of a high-affinity hACE2-binding RBD remains possible. This argument attaches to the lab-origin hypothesis by removing an objection to it, rather than by resting on one of this paper’s own observations.
Validity (step 6)
Reconstruction. This is a rebuttal (undercutter of Andersen’s “no designer could have predicted this RBD”). Premises: (1) SARS-CoV-2 recognises hACE2 more efficiently than SARS-CoV (Wan et al.); (2) chimera work shows bat-CoV spikes bind hACE2 with more plasticity than earlier predicted; (3) Rs3367/WIV1 binds hACE2 and already shares 4 of 6 critical RBD residues with SARS-CoV-2. Load-bearing step: from these, effective hACE2 binding was “foreseeable/selectable in the lab,” so Andersen’s premise is weakened (not that the RBD was designed).
Verdict: approved (checked). Conditional on the premises, the disjunctive conclusion holds. Probed defeater: Andersen’s actual claim was narrower — that computational modelling of the SARS-CoV-2 RBD would not have predicted its specific (non-theoretically-ideal) binding solution — so “more efficient than SARS-CoV” and “related strains bind hACE2” do not fully rebut the rational-design-from-models branch. But the conclusion is a disjunction that also contains “selectable in the lab,” and the lab-selection branch (serial passage / directed evolution) requires no ex-ante prediction at all, so it survives that defeater; premise (2)‘s plasticity plus a related hACE2-binder make selection of a high-affinity RBD a coherent route. Since the statement’s conclusion is only “weakened / foreseeable-or-selectable” — appropriately modest, not “refuted” — the step goes through. Truth of the biological premises is priced at step 8.