Network Pharmacology and Molecular Docking Elucidate the Underlying Pharmacological Mechanisms of the Herb Houttuynia cordata in Treating Pneumonia Caused by SARS-CoV-2

Abstract

Used in Asian countries, including China, Japan, and Thailand, Houttuynia cordata Thumb (H. cordata; Saururaceae, HC) is a traditional herbal medicine that possesses favorable antiviral properties. As a potent folk therapy used to treat pulmonary infections, further research is required to fully elucidate the mechanisms of its pharmacological activities and explore its therapeutic potential for treating pneumonia caused by SARS-CoV-2. This study explores the pharmacological mechanism of HC on pneumonia using a network pharmacological approach combined with reprocessing expression profiling by high-throughput sequencing to demonstrate the therapeutic mechanisms of HC for treating pneumonia at a systemic level. The integration of these analyses suggested that target factors are involved in four signaling pathways, including PI3K-Akt, Jak-STAT, MAPK, and NF-kB. Molecular docking and molecular dynamics simulation were applied to verify these results, indicating a stable combination between four metabolites (Afzelin, Apigenin, Kaempferol, Quercetin) and six targets (DPP4, ELANE, HSP90AA1, IL6, MAPK1, SERPINE1). These natural metabolites have also been reported to bind with ACE2 and 3CLpro of SARS-CoV-2, respectively. The data suggest that HC exerts collective therapeutic effects against pneumonia caused by SARS-CoV-2 and provides a theoretical basis for further study of the active drug-like ingredients and mechanism of HC in treating pneumonia.

Chromosomal-level genome of fish mintHouttuynia cordataThunb. (Saururaceae)

“…Its nutritional profile includes amino acids, crude proteins, lipids, vitamins (mainly vitamin-C), and carbohydrates; and depending on the geographical regions, either the edible rhizomes or leaves of H. cordata will be used in different cuisines 7 . In addition H. cordata has also been widely used in traditional medicine such as Chinese, Indian, and Japanese in the last centuries, and various bioactive compounds such as alkaloids, flavonoids, fatty acids, polyphenols, organic acids, polysaccharides, sterols and volatile oils have also been identified [7][8][9][10][11][12][13][14][15][16] .…”

Herbal medicines exhibit a high affinity for ACE2 in treating COVID-19

“…Yuxingcao is a time-honored herb widely used in Asian countries to treat pneumonia, and it potentially exhibits antiviral activity against enveloped viruses. Some key components of Yuxingcao, such as afzelin, apigenin, kaempferol, and quercetin, have been reported to bind with ACE2 and 3CLpro of SARS-CoV-2 in four signaling pathways, including PI3K-Akt, Jak-STAT, MAPK, and NF-kB (22).…”

Identification of host genomic biomarkers from multiple transcriptomics datasets for diagnosis and therapies of SARS-CoV-2 infections

“…GSE147507 raw count data contained 6 samples (3 COVID-19 patients and 3 NHBE samples) [15,23]. GSE152075 is a microarray data containing 430 COVID-19 infected samples and 54 negative samples [16,[24][25][26]. The microarray dataset GSE152075 was downloaded using the Bioconductor package GEOquery, and the batch effect of this dataset was removed by using the R package sva via Combat_seq [27,28].…”