Coronavirus is a single-stranded righteous RNA virus as well as an enveloped virus. It consists of alpha coronaviruses (α-CoV), beta coronaviruses (β-CoV), gamma coronaviruses (γ-CoV) and delta coronaviruses (δ-CoV). Specifically, Transmissible gastroenteritis virus (TGEV) and Porcine delta coronavirus (PDCoV) belong to α-CoV and δ-CoV, respectively. They cause infectious intestinal disease and high mortality in pigs.

However, the viral lipid membrane and virus-cell fusion ability of enveloped viruses are the basis of their extreme pathogenicity. The enveloped virus replicates in the host cell, recruits proteins to the host cell membrane, and then uses the host cell membrane to germinate. This kind of viral lipid membrane lacks the biogenic repair ability of cell membranes, leaving a breakthrough for the research of broad-spectrum antiviral agents. Existing antiviral reagents, and lack of accurate recognition of host and viral proteins, will have side effects on cells. The small antiviral molecule LJ001, produced by interfering with virus-cell fusion meets this need, specifically targeting the viral lipid membrane.

LJ001 targets the viral lipid membrane specifically and inhibits virus replication.

LJ001 shows antiviral activity in vitro with low cytotoxicity (CC₅₀=146.4 μM, in porcine testicular cells). In anti-TGEV and PDCoV assays, LJ001 (3.125 and 12.5μM; 24 h) significantly reduces virus titers. It inhibits viral replication by inhibiting viral RNA and protein synthesis. LJ001 inhibits viral transmission, blocking the entry of enveloped viruses after viral binding but before virus-cell fusion. LJ001 (20 mg/kg; p.o.; once daily for 7 days) is also an orally active anti-viral agent.

Above all, LJ001 is an orally active and specific inhibitor of the enveloped virus, with broad-spectrum anti-bacterial activity. LJ001 targets viral membranes and inhibits viral RNA and protein synthesis.

Reference:

[1] Zhang Y, et al. Virus Res. 2020 Nov;289:198167.

[2] Wolf MC, et al. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3157-62.