Frontiers in microbiologyAug 28, 2025

PB28, a sigma-1 receptor blocker, may fight a wide range of coronaviruses

Long Covid Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 2, 2026

Abstract

PB28 demonstrates robust antiviral activity against α-, β-, and γ-coronaviruses.

PB28 effectively inhibits the replication of various coronaviruses, including SARS-CoV-2 and its variants, as well as other α- and γ-coronaviruses.
Molecular docking analysis indicates a stable interaction between PB28 and the sigma-1 receptor.
Administration of PB28 in mice infected with SARS-CoV-2 Delta significantly reduced viral loads and improved survival rates.
Treatment with PB28 in chicken embryos and neonatal chicks infected with IBV enhanced survival and reduced tissue damage.
The antiviral efficacy of PB28 is likely mediated through modulation of the sigma-1 receptor.

Simplified

The continuous evolution of coronaviruses poses persistent and severe threats to both human and animal health. While α- and β-coronaviruses mainly infect mammals, including humans, γ-coronaviruses predominantly infect poultry, causing substantial economic losses. Their rapid mutation rates and wide host tropism underscore the urgent demand for pan-coronavirus therapeutics. Here, we systematically investigated the antiviral potency and mechanism of action of PB28, a selective sigma-1 receptor antagonist, across α-, β-, and γ-coronaviruses. Molecular docking predicted a stable interaction between PB28 and the sigma-1 receptor. PB28 exhibits robustantiviral activity, effectively inhibiting the replication of β-coronaviruses (SARS-CoV-2 and its Beta, Delta, and Omicron variants; HCoV-OC43), α-coronaviruses (PEDV and TGEV), and γ-coronaviruses (IBV). Broad-spectrum antiviral efficacy is further validated by viral titration assays., PB28 administration in K18-hACE2 mice infected with SARS-CoV-2 Delta and BALB/c mice infected with HCoV-OC43 led to significantly reduced viral loads, attenuated multi-organ pathology, and improved survival and body weight maintenance. In parallel, PB28 treatment in IBV-infected chicken embryos and neonatal chicks enhanced survival, supported embryogenesis, and alleviated tissue damage. Collectively, PB28 demonstrates cross-genus antiviral efficacy, likely mediated through modulation of the sigma-1 receptor. These findings highlight PB28 as a promising lead compound for the development of pan-coronavirus therapeutics. in vitro In vivo

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PB28, a sigma-1 receptor blocker, may fight a wide range of coronaviruses

Abstract

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