Figure 1.
In Vivo efficacy of favipiravir, molnupiravir, and nirmatrelvir monotherapy regimen in K18-hACE2 mice against SARS-CoV-2 Delta VOC
(A) Experimental design for monitoring therapeutic efficacy of indicated drugs and neutralizing antibody (nAb) CV3-1 in K18-hACE2 mice challenged intranasally (i.n.) with 1 × 105 PFU of reporter SARS-CoV-2-Delta-nLuc VOC. favipiravir (600 mg/kg body weight, b.w.) and nAb CV3-1 (12.5 mg/kg b.w.) were administered intraperitoneally (i.p.) while molnupiravir (250 mg/kg) and nirmatrelvir (650 mg/kg) given via oral gavage (oral) under a therapeutic regimen starting 0.25 dpi. All drugs except nAb (single dose) were given twice a day (BID) for 6 days. Vehicle-treated (Vehicle) mice (n = 5–10) were used as control.
(B) Representative BLI images of SARS-CoV-2-Delta-nLuc-infected mice under indicated treatment regimens in ventral (v) and dorsal (d) positions. Mice that succumb and survive challenge are shown separately for clarity.
(C and D) Temporal quantification of nLuc signal as flux (photons/sec) computed non-invasively.
(E) Temporal changes in mouse body weight with initial body weight set to 100% for an experiment shown in A.
(F) Kaplan-Meier survival curves of mice (n = 5 per group) statistically compared by log rank (Mantel-Cox) test for experiment as in A.
(G and H) Fold changes in indicated cytokine mRNA expression in brain and lung tissues of mice under specified treatment regimens after necropsy upon death or at 14 or 22 dpi in the surviving animals. Data were normalized to Gapdh mRNA in the same sample and that in non-infected mice after necropsy.
Scale bars in (B) denote radiance (photons/s/cm2/steradian). Grouped data in (C-E) and (G and H) were analyzed by two-way ANOVA followed by Tukey’s multiple comparison tests. Statistical significance for group comparisons to Vehicle are shown in black, with favipiravir are shown in blue, with molnupiravir are shown in purple, with nirmatrelvir are shown as red and with CV3-1 are shown as pink. ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001; ∗∗∗∗, p < 0.0001; ns not significant; mean values ±SD are depicted. Points enclosed in dotted circles and red cross signs are used to indicate mice that succumbed to infection. b.w.: body weight.