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INTRODUCTION Immunity boosting has emerged as a global strategy to fight the SARS-CoV-2 pandemic situation. In India, AYUSH systems of medicine have been promoted as an immune-protection strategy. Andrographis paniculata (Burm. F) Nees (AP) mentioned in Ayurveda has been widely used for treating sore throat, flu, and upper respiratory tract infections which may provide possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways. OBJECTIVES The present work uses liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics and combination synergy analysis based on network pharmacology to mine multimode evidence to understand the possible mechanism of action, diseases association, protein-protein interaction and major pathways involved therein. MATERIAL AND METHODS Metabolite profiling was performed by Agilent QTOF LC-MS/MS system. Network pharmacology analysis was performed by using functional annotation analysis based on databases like Binding DB, STRING, DAVID and KEGG for further data mining. Further combination synergy was evaluated using \'neighbourhood approach\' and networks were constructed through Cytoscape 3.2.1. RESULTS The molecules from kalmegh provides immune-protection and anti-viral response via involving different pathways, like toll-like receptor pathway, PI3/AKT pathway and MAP kinase pathways against COVID-19 infection. The KEGG analysis showed that in a vast majority of the most enriched pathways, AP were associated with viral infections and upper respiratory tract infections. CONCLUSIONS The results suggest a synergy between andrographolide and other molecules identified as safe and efficacious anti-inflammatory agent having effects on upper respiratory tract infections and can significantly decrease the production of cytokines and pro-inflammatory factors in viral infections.
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