Disrupting autorepression circuitry generates ‘‘open-loop lethality’’ to yield escape-resistant antiviral agents

(Cell 185, 2086–2102.e1–e11;June 9, 2022)

Our paper reported a class of antiviral agents that operate by disrupting transcriptional negative feedback circuits to break homeostasis and thereby increase viral transactivators above a cytotoxic threshold (termed “open-loop lethality”). During the preparation of Figure S1A and the corresponding equations for numerical simulations of feedback disruption, we inadvertently inserted the equations from a preliminary model, not the finalized version. The correct equations should read:

$$\frac{d\left[IE86\right]}{dt}={\alpha }_0+{\alpha }_1\frac{{k_1}^{h_1}}{{\left[IE86\right]}^{h_1}+{k_1}^{h_1}}·\frac{{\left[IE86\right]}^{h_3}}{{\left[IE86\right]}^{h_3}+{k_3}^{h_3}}-h_1{k}_2{\left[IE86\right]}^{h_1}\left[FD\right]+h_1{k}_{–2}\left[Complex\right]-{\gamma }_1\left[IE86\right]$$

$$\frac{d\left[FD\right]}{dt}={-k}_2{\left[IE86\right]}^{h_1}\left[FD\right]+k_{–2}\left[Complex\right]$$

$$\frac{d\left[Complex\right]}{dt}=k_2{\left[IE86\right]}^{h_1}\left[FD\right]{-k}_{–2}\left[Complex\right]$$

With parameter values: ${\alpha }_0=0.4$, ${\alpha }_1=9.7$, $k_1=8.1$, $k_2=4.4$, $k_{-2}=6.8$, $k_3=6.9$, and ${\gamma }_1=0.61$; all other parameter values were as specified. We have updated the graphed data in Figure S1A to reflect the correct equations. The error does not affect the conclusions of the paper, in that the numerical simulations from both the preliminary and finalized equations generate qualitatively similar (i.e., bimodal) results. The original article has been corrected online. We apologize for any confusion the errors may have caused.

Figure S1A.

Simulations and in vitro analyses of FD DNA duplexes (corrected)

Figure S1A.

Simulations and in vitro analyses of FD DNA duplexes (original)