Andrographis paniculata standardized extract attenuates transcriptome, proteome, and metabolome changes caused by SARS-CoV-2 infection in golden hamster kidney

SARS-CoV-2 was the cause of the COVID-19 global pandemic that resulted in millions of deaths worldwide. SARS-CoV-2 infection is often accompanied by renal manifestations such as acute kidney injury and kidney fibrosis, however there is a lack of effective treatment options that also address renal involvement. In this study, golden hamsters were inoculated with Delta variant SARS- CoV-2, and given either vehicle or Andrographis paniculata (AP) standardized extract as treatment. Hamster kidney tissues were then subjected to transcriptomics, proteomics, and metabolomics analysis. Results showed that AP potentially ameliorates kidney fibrosis mediated by ECHS1-induced mTOR activation and LHX1-HDAC8 promotion. This was supported by observations of lipid metabolism alterations that may have been a result of mTOR activation in metabolomics study. Transcriptomics analysis revealed less enrichment of viral infection pathways in AP-treated groups. Overall, AP appears to attenuate SARS-CoV-2 infection and development of kidney fibrosis. The animal study was conducted within an AAALAC International-accredited facility and abided to ARRIVE guidelines. Briefly, 8-week old male golden hamsters were split into 5 groups, which were: 1. SARS-CoV-2- infected, orally received vehicle treatment (2 mL/kg/day dimethyl sulfoxide), and sacrificed 1 day post inoculation (Delta control day 1), 2. Delta control day 3, 3. SARS-CoV-2-infected, orally administered 1000 mg/kg/day Andrographis paniculata (AP) 95% ethanol standardized extract, and sacrificed 1 day post inoculation (Delta AP day 1), 4. Delta AP day 3, and 5. Delta AP day 7. Kidney tissue was collected during necropsy.