Potential mechanism prediction of Cold-Damp Plague Formula against COVID-19 via network pharmacology analysis and molecular docking

Abstract

Background: Coronavirus disease 2019 (COVID-19) is a new global public health emergency. The therapeutic benefits of Cold-Damp Plague Formula (CDPF) against COVID-19, which was used to treat "cold-dampness stagnation in the lung" in Trial Versions 6 and 7 of the "Diagnosis and Treatment Protocol for COVID-19", have been demonstrated, but the effective components and their mechanism of action remain unclear. Methods: In this study, a network pharmacology approach was employed, including drug-likeness evaluation, oral bioavailability prediction, protein-protein interaction (PPI) network construction and analysis, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and virtual docking, to predict the bioactive components, potential targets, and molecular mechanism of CDPF for COVID-19 treatment. Results: The active compound of herbs in CDPF and their candidate targets were obtained through database mining, and an herbs-ingredients-targets network was constructed. Subsequently, the candidate targets of the active compounds were compared to those relevant to COVID-19, to identify the potential targets of CDPF for COVID-19 treatment. Subsequently, the PPI network was constructed, which provided a basis for cluster analysis and hub gene screening. The seed targets in the most significant module were selected for further functional annotation. GO enrichment analysis identified four main areas: (1) cellular responses to external stimuli, (2) regulation of blood production and circulation, (3) free radical regulation, (4) immune regulation and anti-inflammatory effects. KEGG pathway analysis also revealed that CDPF could play pharmacological roles against COVID-19 through "multi components-multi targets-multi pathways" at the molecular level, mainly involving anti-viral, immune-regulatory, and anti-inflammatory pathways; consequently, a "CDPF-herbs-ingredients-targets-pathways-COVID-19" network was constructed. In hub target analysis, the top hub target IL6, and ACE2, the receptor via which SARS-CoV-2 typically enters host cells, were selected for molecular docking analyses, and revealed good binding activities. Conclusions: This study revealed the active ingredients and potential molecular mechanism by which CDPF treatment is effective against COVID-19, and provides a reference basis for the wider application and further mechanistic investigations of CDPF in the fight against COVID-19.

The direct evidence and mechanism of traditional Chinese medicine treatment of COVID-19

“…The active ingredients and candidate targets of HSYF were obtained through database mining, and a "HSYF–herbal-components–targets–pathways–COVID-19" network was constructed. In the central target analysis, the highest central target IL-6 and ACE2 were selected for molecular docking analysis, which revealed good binding activity [ 126 ].…”

Understanding COVID-19 in Wuhan From the Perspective of Cold-Dampness: Clinical Evidences and Mechanisms

“…Inhibiting this may decrease inflammation in patients with COVID-19. For mild and moderate COVID-19 cases, HSYF successfully reduced the progression to severe status, and alleviated symptoms in patients by exerting anti-viral effect, immune regulation and anti-inflammatory pathways ( 90 ). A correlation between blood glucose control and prognosis in patients with co-existing COVID-19 and diabetes has been reported ( 123 ); HSYF could target the AGE-RAGE signaling pathway in such patients.…”

“…HSYF was used to treat “cold–dampness stagnation in the lung” in COVID-19. Network enrichment analysis showed that HSYF components could to interleukin (IL)-6 and ACE2 ( 90 ). Since IL6 plays a central role in the acute inflammatory response, its potential inhibition could significantly improve prognosis in COVID-19 patients ( 91 ).…”

“…A network pharmacology study showed that HSYF could play a role in immune regulation through proinflammatory and anti-inflammatory cytokines and exerts antiviral effects by regulating the hub targets IL6, TNF, IL10, mitogen activated protein kinase- (MAPK)-8, MAPK3, chemokine (CXCL)-8, caspase (CASP)-3, Prostaglandin-Endoperoxide Synthase (PTGS)-2, tumor protein p (TP)-53, and MAPK1 ( 90 ). IL6 and TNF play key roles in the cytokine storm.…”

Based on network pharmacology and molecular docking to explore the Traditional Chinese Medicine anti-influenza mechanisms:Chinese protocol for diagnosis and treatment of influenza.

“…With the rapid development of bioinformatics, network pharmacology has become a new way to effectively reveal the molecular and pharmacological mechanisms of TCM formulae, and it will also become a new paradigm for TCM research [3][4][5][6][7]. The network pharmacological studies on the anti-influenza effects of compound Artemisia annua, Jingyin granule and Reduning injection have been carried out [8][9][10].…”