Orally administered BZL-sRNA-20 oligonucleotide targeting TLR4 effectively ameliorates acute lung injury in mice

Dandan Zhao # 1, Yuhao Qin # 1, Jiaqi Liu # 1, Kegong Tang 1, Shuaiyao Lu 2, Zirui Liu 3, Yexuan Lin 1, Cong Zhang 1 4, Fengming Huang 1, Jiahui Chang 1, Chang Li 3, Mingyao Tian 3, Yiming Ma 1, Xiaoyun Li 1, Congzhao Zhou 4, Xiao Li 5, Xiaozhong Peng 6, Ningyi Jin 7, Chengyu Jiang 8

Sci China Life Sci. 2023 Feb 13;1-11. doi: 10.1007/s11427-022-2219-0.

PMID: 36808291

Abstract

The global COVID-19 pandemic emerged at the end of December 2019. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are common lethal outcomes of bacterial lipopolysaccharide (LPS), avian influenza virus, and SARS-CoV-2. Toll-like receptor 4 (TLR4) is a key target in the pathological pathway of ARDS and ALI. Previous studies have reported that herbal small RNAs (sRNAs) are a functional medical component. BZL-sRNA-20 (Accession number: B59471456; Family ID: F2201.Q001979.B11) is a potent inhibitor of Toll-like receptor 4 (TLR4) and pro-inflammatory cytokines. Furthermore, BZL-sRNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (poly (I:C)). We found that BZL-sRNA-20 rescued the viability of cells infected with avian influenza H5N1, SARS-CoV-2, and several of its variants of concern (VOCs). Acute lung injury induced by LPS and SARS-CoV-2 in mice was significantly ameliorated by the oral medical decoctosome mimic (bencaosome; sphinganine (d22:0)+BZL-sRNA-20). Our findings suggest that BZL-sRNA-20 could be a pan-anti-ARDS ALI drug.