tetano
Editor, Senior Moderator
Antiviral Res
. 2025 Mar 28:237:106154.
doi: 10.1016/j.antiviral.2025.106154. Online ahead of print. Comprehensive preclinical characterization of IPB29, a pan-coronavirus fusion inhibitor under clinical trials
Yuanmei Zhu[SUP] 1 [/SUP], Zhongcai Gao[SUP] 2 [/SUP], Xiaoli Feng[SUP] 3 [/SUP], Yue Hu[SUP] 1 [/SUP], Nian Liu[SUP] 1 [/SUP], Chao Liu[SUP] 2 [/SUP], Qiaojiang Yang[SUP] 3 [/SUP], Qingcui Zou[SUP] 3 [/SUP], Minghua Li[SUP] 4 [/SUP], Gengshen Song[SUP] 5 [/SUP], Yuxian He[SUP] 6 [/SUP]
Affiliations
IPB29 is a lipopeptide-based coronavirus fusion inhibitor with the potent, broad-spectrum antiviral activity, and it has already been advanced to phase III clinical trials for the treatment of SARS-CoV-2 infection. We recently reported its design strategy and initial preclinical characterization; herein, we focused on characterizing its efficacies against newly-emerged Omicron variants, as well as its chronic general toxicity, toxicokinetics, immunogenicity, and reproductive toxicity in animal models. As anticipated, IPB29 demonstrated improved activity in inhibiting JN.1 and KP.2 variants, effectively blocking cell fusion and pseudovirus infections. Nebulized inhalation of IPB29 exhibited high therapeutic efficacy against live BA.5 and EG.5.1 infections in Syrian hamsters. The 26-week toxicity studies revealed that nebulized IPB29 has a favorable safety profile, with well-characterized toxicokinetics in SD rats and Beagle dogs. Notably, short-term nebulization of IPB29 did not elicit anti-drug antibody (ADA) responses in either species. However, IPB29-specific antibodies were detected after long-term administration. Finally, a three-stage reproductive toxicity study in SD rats indicated that IPB29 had no significant toxic effects on fertility, embryo-fetal development, or the development of offspring. In summary, our findings demonstrate that IPB29 is a safe and effective SARS-CoV-2 inhibitor with promising potential for clinical applications.
Keywords: Coronavirus; Fusion inhibitor; IPB29; Lipopeptide; SARS-CoV-2.
. 2025 Mar 28:237:106154.
doi: 10.1016/j.antiviral.2025.106154. Online ahead of print. Comprehensive preclinical characterization of IPB29, a pan-coronavirus fusion inhibitor under clinical trials
Yuanmei Zhu[SUP] 1 [/SUP], Zhongcai Gao[SUP] 2 [/SUP], Xiaoli Feng[SUP] 3 [/SUP], Yue Hu[SUP] 1 [/SUP], Nian Liu[SUP] 1 [/SUP], Chao Liu[SUP] 2 [/SUP], Qiaojiang Yang[SUP] 3 [/SUP], Qingcui Zou[SUP] 3 [/SUP], Minghua Li[SUP] 4 [/SUP], Gengshen Song[SUP] 5 [/SUP], Yuxian He[SUP] 6 [/SUP]
Affiliations
- PMID: 40158858
- DOI: 10.1016/j.antiviral.2025.106154
IPB29 is a lipopeptide-based coronavirus fusion inhibitor with the potent, broad-spectrum antiviral activity, and it has already been advanced to phase III clinical trials for the treatment of SARS-CoV-2 infection. We recently reported its design strategy and initial preclinical characterization; herein, we focused on characterizing its efficacies against newly-emerged Omicron variants, as well as its chronic general toxicity, toxicokinetics, immunogenicity, and reproductive toxicity in animal models. As anticipated, IPB29 demonstrated improved activity in inhibiting JN.1 and KP.2 variants, effectively blocking cell fusion and pseudovirus infections. Nebulized inhalation of IPB29 exhibited high therapeutic efficacy against live BA.5 and EG.5.1 infections in Syrian hamsters. The 26-week toxicity studies revealed that nebulized IPB29 has a favorable safety profile, with well-characterized toxicokinetics in SD rats and Beagle dogs. Notably, short-term nebulization of IPB29 did not elicit anti-drug antibody (ADA) responses in either species. However, IPB29-specific antibodies were detected after long-term administration. Finally, a three-stage reproductive toxicity study in SD rats indicated that IPB29 had no significant toxic effects on fertility, embryo-fetal development, or the development of offspring. In summary, our findings demonstrate that IPB29 is a safe and effective SARS-CoV-2 inhibitor with promising potential for clinical applications.
Keywords: Coronavirus; Fusion inhibitor; IPB29; Lipopeptide; SARS-CoV-2.