Conformational disruption of metastable Spike complex. We hypothesize that the observed irreversible inactivation of SARS-CoV-2 Spike by lectins may be rooted in the intrinsic metastability of the Spike protein trimer. Dynamic equilibrium between multiple conformational states in the spike complex has been observed previously , and enables the quaternary structure of the Spike to undergo large-scale conformational rearrangement, upon receptor engagement, to liberate and utilize the fusion peptide in the S2 subunit to effect virus-cell membrane fusion during infection. Thus, conformational metastability is a necessary property of the virus Spike to enable infection. We speculate that the Spike conformational plasticity integral for infection could be hijacked by the engagement of the spike by CV-N and GRFT, to drive the conformationally dynamic S complex into a nonfunctional state. Intriguingly, irreversible structural changes in the Spike protein complex by ACE2 decoy receptors have been reported recently . While the relatedness of structural changes caused by lectins compared to those caused by decoy receptors remains to be understood, both may well be dependent on spike metastability. An alternative consideration, which cannot be discounted, is that CV-N does remain attached to spike after washout, though perhaps obscured by the same non-spike binding as exhibited by the spike-negative virus-like particles. Instead of forcing a conformational change in spike, attached CV-N may function as an inactive state stabilizer of spike, rendering it unable to rearrange into downstream infection-productive configurations.