Network Pharmacology and Molecular Docking Analysis of Plumula Nelumbinis Alkaloids as Potential Therapeutics for COVID-19

• 1、School of Biomedical and Pharmaceutical Sciences,Guangdong University of Technology,Guangzhou,510006

Abstract：Peanut alkaloid (PNA), the main active component of Nelumbo nucifera (lotus), has been demonstrated to possess anti-inflammatory and antiviral properties, making it a potential therapeutic candidate for coronavirus disease 2019 (COVID-19). Protein targets of PNA were screened through multiple databases, and a compound-target network was constructed using Cytoscape. COVID-19-related disease targets were retrieved from the Genecards database, and the intersection between compound targets and disease targets was analyzed. A protein-protein interaction (PPI) network was constructed using the STRING database, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding affinities between active compounds and key targets were evaluated through molecular docking and MM/GBSA simulations. Six key targets of PNA were identified, including ACE2, TMPRSS2, DPP4, AKT1, JAK1, and MAPK1, which are involved in signaling pathways such as AGE-RAGE, PI3K-Akt, TNF, MAPK, Toll-like receptor, and JAK-STAT. Molecular docking and MM/GBSA analyses confirmed stable binding interactions between PNA compounds and the aforementioned targets. This study elucidates the molecular mechanism of PNA in intervening against COVID-19 and identifies key targets including ACE2, TMPRSS2, DPP4, AKT1, JAK1, and MAPK1. The findings lay a foundation for subsequent research on the therapeutic potential of PNA and provide guidance for the development of compounds targeting COVID-19-related proteins.

Keywords： Plumula Nelumbinis Alkaloids COVID-19 Network pharmacology Signal pathway Computer-aided drug design