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. 2022 Oct 28:9:1002488.
doi: 10.3389/fvets.2022.1002488. eCollection 2022.

Effect of GS-441524 in combination with the 3C-like protease inhibitor GC376 on the treatment of naturally transmitted feline infectious peritonitis

Jinbao Lv  1 , Yang Bai  1 , Yingyun Wang  1 , Liu Yang  1 , Yipeng Jin  1 , Jun Dong  1
Affiliations

Effect of GS-441524 in combination with the 3C-like protease inhibitor GC376 on the treatment of naturally transmitted feline infectious peritonitis

Jinbao Lv et al. Front Vet Sci. .

Abstract

Objectives: The main objectives of this study were to investigate the efficacy of the nucleotide analog GS-441524 in combination with the 3C-like protease inhibitor GC376 for the treatment of naturally aquired feline infectious peritonitis (FIP) and to test whether their combination shortens the dosing period and improves the cure rate.

Methods: In total, 46 FIP-affected cats were enrolled in this experiment, including 36 with wet FIP (29 with abdominal effusion, six with thoracic effusion, and one with thoracic+abdominal effusion), and 10 with dry FIP. The cats were aged from 3 to 96 months. Thoracic+abdominal effusion, lymph-node puncture fluid and perirenal puncture fluid was collected from the affected cats for qPCR testing, and all 46 cats were positive for feline coronavirus (FCoV). The cats divided into different dose groups, all treated for 4 weeks: group 1 (GS-441524, 5 mg/kg.sc.q.24 h; GC376, 20 mg/kg.sc.q.12 h), group 2 (GS-441524, 2.5 mg/kg.sc.q.24 h; GC376, 20 mg/kg.sc.q.12 h), group 3 (GS-441524, 2.5 mg/kg.sc.q.24 h; GC376, 10 mg/kg.sc.q.12 h), and group 4 (GS-441524, 5 mg/kg.sc.q.24 h; GC376, 10 mg/kg.sc.q.12 h).

Results: After the 4-week combination treatment, 45 of the 46 (97.8%) cats survived, and 43 of those became clinically normal. Two cats required longer (7 to 12 weeks) treatment to achieve full recovery. As of writing (10 months after completion of the trial), all 45 cats were alive and no relapse was observed.

Conclusions and relevance: GS-441524 combined with GC376 can be safely and effectively used to treat FIP and reduces the treatment period to 4 weeks, with an excellent cure rate.

Keywords: GC376; GS-441524; combination; feline infectious peritonitis; field experiment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Age proportion of the cats. (B) Sex proportion of the cats.
Figure 2
Figure 2
The pie chart shows the number and proportion of different clinical forms of infectious peritonitis (FIP) in cats from the 4 groups.
Figure 3
Figure 3
Mean body temperature, body weight variation and standard error for 4 groups cats that completed 4 weeks of treatment. (A) Body temperature. (B) Body weight.
Figure 4
Figure 4
Mean WBC changes and standard error for 4 groups cats that completed 4 weeks of treatment. WBC, white blood cell.
Figure 5
Figure 5
Mean HGB, HCT variation and standard error for 4 groups cats that completed 4 weeks of treatment. (A) HGB. (B) HCT. HGB, hemoglobin; HCT, hematocrit.
Figure 6
Figure 6
Mean TP, GLOB, ALB, A:B changes and standard error for 4 groups cats that completed 4 weeks of treatment. (A) TP. (B) GLOB. (C) ALB. (D) A:G. TP, total protein; GLOB, globulin; ALB, albumin; A:G, albumin–globulin ratio.
Figure 7
Figure 7
Mean TBIL changes and standard error for 4 groups cats that completed 4 weeks of treatment. TBIL, total bilirubin.
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