Mink- and ferret-associated spike mutations allow more efficient entry into cells expressing the ferret ACE2 receptor
(A) Pseudovirus entry in human or ferret ACE2-expressing cells. Mutant SARS-CoV-2 spike-containing pseudovirus entry into HEK 293Ts expressing human or ferret ACE2 or empty vector. Entry normalized to signals from human ACE2 expressing cells. Each data point indicates mean value taken from a completely independent repeat (n ≥ 3). Data plotted as mean ± s.d. Statistics were determined by comparing log-transformed values of ferret ACE2 entry using a one-way ANOVA with multiple comparisons against the WT. ∗0.05 ≥ p > 0.01; ∗∗0.01 ≥ p > 0.001; ∗∗∗0.001 ≥ p > 0.0001; ∗∗∗∗p ≤ 0.0001.
(B and C) Entry of SARS-CoV-2 spike mutant-expressing lentiviral pseudotypes into BHK-21 cells expressing different mammalian ACE2 proteins. Pseudovirus shown contain either D614G (B) or D614 (C). Representative repeat shown from n ≥ 3 repeats. Data plotted as mean ± s.d.
(D) Structure of ACE2/Spike RBD interface showing key mink-adaptation residues and nearby residues that differ in mustelid and human ACE2. Figure made using PyMOL (Schrödinger) and PDB: 7A94(Benton et al., 2020).