Table 9. Nanobody synergy of neutralization activity; related to Figure 7.

Parameters from modeling the synergy observed for the indicated nanobody pairs. Multidimensional synergy of combinations (MuSyC), equivalent dose, and Bivariate Response to Additive Interacting Doses (BRAID) models were used to determine if statistically significant synergy was evident from the neutralization response in a 2D grid of nanobody concentrations.

First nanobody	Second nanobody	(Nanobody #1) experimental range	(Nanobody #2) experimental range	h1	h2	C1 (nM)	C2 (nM)	alpha12	alpha21	a12	a21	Kappa
S1-23	S1-27	4.1 pM to 717 nM, 0 µM	3.4 pM to 600 nM, 0 µM	1.80	1.46	25.0	20.0	n.s.	n.s.	n.s.	n.s.	n.s
S1-1	S1-23	2.2 pM to 387 nM, 0 µM	4.1 pM to 717 nM, 0 µM	0.93	1.51	4.2	18.6	21.4	31.8	Synergy	Synergy	Synergy
S1-RBD-15	S1-23	3 pM -to 527 nM, 0 µM	4.1 pM to 717 nM, 0 µM	1.32	1.42	3.7	10.3	300.0	10.2	Synergy	Synergy	Synergy
S1-RBD-15	S1-RBD-23	3 pM to 527 nM, 0 µM	1.8 pM to 325 nM, 0 µM	1.44	1.00	4.4	7.9	523	2.9	Synergy	n.s.	Synergy
S1-23	S1-46	4.1 pM to 717 nM, 0 µM	7.55 pM to 1.34 µM, 0 µM	1.76	0.75	3.3	273.0	50.1	1.0	Synergy	Antagonism	Synergy
S1-RBD-15	S1-46	39.7 pM to 7.04 µM, 0 µM	7.55 pM to 1.34 µM, 0 µM	1.10	0.75	4.9	164	10.7	0.9	Synergy	Antagonism	Synergy
S1-23	S2-10-dimer	4.1 pM to 717 nM, 0 µM	5.1 pM to 897 nM, 0 µM	1.48	1.14	5.4	45.4	4232.0	2.8	Synergy	n.s.	Synergy
S1-49	S1-1	2.1 pM to 367 nM, 0 µM	2.2 pM to 387 nM, 0 µM	0.77	1.62	152.0	1.7	1,147	18.1	Synergy	Synergy	Synergy
S1-49	S1-RBD-15	2.1 pM to 367 nM, 0 µM	39.7 pM to 7.04 µM, 0 µM	0.85	1.20	629.0	2.2	243.5	20.3	n.s.	Synergy	Synergy
S1-RBD-15	S2-10-dimer	3 pM to 527 nM, 0 µM	5.1 pM to 897 nM, 0 µM	1.57	1.00	1.9	56	4,110	2.2	Synergy	Synergy	Synergy

n.s., not significant; h1, h2, Hill slope; C1, C2, IC50 (nM);alpha12, alpha21, synergistic/antagonistic fold change of potency from MuSyC model; a12, a21, equivalent dose model synergy/antagonism; kappa, BRAID model synergy/antagonism.