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. 2020 Dec 8;16(12):e1008461. doi: 10.1371/journal.pcbi.1008461

Table 1. Experimental evidence of Bliss synergy.

We computed the extent of synergy from reported data on the effects of the individual drugs and the combination. The difference between the expected effect of the combination in terms of the fraction unaffected (fu) based on Bliss independence and the effect observed yielded the extent of synergy. Infection was by viruses pseudotyped with either SARS-CoV-2 S (denoted SARS-2-S) or SARS-CoV S (denoted SARS-S) protein. The experimental observations (fu(DT), fu(DC), and fu(DT,DC)) reported are reproduced for convenience and using which we computed the extent of synergy (βBliss).

Infection Cell line Drug combination fu(DT) fu(DC) fu(DT,DC) βBliss Ref.
Expected Observed
SARS-2-S Vero-TMPRSS2 Camostat (DT)
+
E-64d (DC)
0.43 0.79 0.34 0.08 0.26 [21]
SARS-S Vero-TMPRSS2 Camostat (DT)
+
E-64d (DC)
0.53 0.8 0.42 0.02 0.4 [21]
SARS-S HeLa-ACE2-TMPRSS2 Camostat (DT)
+
EST (DC)
0.42 0.66 0.28 0.06 0.22 [28]
SARS-S HeLa-ACE2-TMPRSS2 Camostat (DT)
+
Bafilomycin (DC)
0.42 0.6 0.25 0.08 0.17 [28]

*Note that synergy is not expected in cell lines such as Calu-3 and Caco-2 where one pathway dominates (see Fig 6).