"Fei Yan No. 1" as a Combined Treatment for COVID-19: An Efficacy and Potential Mechanistic Study

Abstract

There has been a large global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), representing a major public health issue. In China, combination therapy, including traditional Chinese medicine (TCM) as a treatment for COVID-19 has been used widely. "Fei Yan No. 1" (QFDYG) is a formula recommended by the Hubei Government to treat COVID-19. A retrospective study of 84 COVID-19 patients from Hubei Provincial Hospital of TCM and Renmin Hospital of Hanchuan was conducted to explore the clinical efficacy of QFDYG combination therapy. TCMSP and YaTCM databases were used to determine the components of all Chinese herbs in QFDYG. Oral bioavailability (OB) ≥ 30% and drug-like (DL) quality ≥ 0.18 were selected as criteria for screening the active compounds identified within the TCMSP database. The targets of active components in QFDYG were determined using the Swiss TargetPrediction (SIB) and Targetnet databases. The STRING database and the Network Analyzer plugin in Cytoscape were used to obtain protein-protein interaction (PPI) network topology parameters and to identify hub targets. Gene Ontology (GO) enrichment was conducted using FunRich version 3.1.3, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment using ClueGO version 2.5.6 software. PPI and compound-pathway (C-T) networks were constructed using Cytoscape 3.6.0. Compared with the control group, combined treatment with QFDYG resulted in a significantly higher rate of patients recovering from symptoms and shorter the time. After 14 days of treatment, QFDYG combined treatment increased the proportion of patients testing negative for SARS-CoV-2 nucleic acid by RT-PCR. Compared with the control group, promoting focal absorption and inflammation as viewed on CT images. GO and KEGG pathway enrichment indicated that QFDYG principally regulated biological processes, such as inflammation, an immune response, and apoptosis. The present study revealed that QFDYG combination therapy offered particular therapeutic advantages, indicating that the theoretical basis for the treatment of COVID-19 by QFDYG may play an antiviral and immune response regulation through multiple components, targets, and pathways, providing reference for the clinical treatment of COVID-19.

Keywords: COVID-19; Fei Yan NO1; SARS-CoV-2; clinical efficacy; network pharmacology.

Figure 1

Clinical efficacy.

Figure 2

Data collection for the treatment of COVID-19 patients.

Figure 3

SARS-CoV-2 nucleic acid by RT-PCR between two groups (P < 0.05).

Figure 4

The results of chest CT scan with QFDYG combined therapy. A, B and C represent different slices. Mild patient: A 55-year-old female with bilateral pulmonary infiltrate prior to treatment with ST+QFDYG observed in A and B slices. Clear absorption of bilateral pulmonary infiltrate was observed by day 9. Severe patient: A 50-year-old female with shortness of breath and hypertension at the initiation of treatment with ST+QFDYG. Images display bilateral pulmonary infiltrate in A, B and C slices over an area larger than that of a mild patient. Marked absorption of the bilateral pulmonary infiltrate was observed by day 11, with only a few small patches of faint shadow remaining.

Figure 5

PPI network of candidate target. The colors of the nodes are illustrated from red to orange to yellow in descending order of degree values.

Figure 6

GO enrichment of the candidate targets. (A) Biological process of the candidate targets. (B) Cellular component of the candidate targets. (C) Molecular function of the candidate targets.

Figure 7

KEGG pathway enrichment of the potential targets (A). Pathways and associated genes relationships network (B).

Figure 8

Drug-compound-target network of QFDYG. The red square nodes represent Chinese herbs. and the circular nodes represent active compounds and targets. Nodes size and color are illustrated from dark orange to yellow to green in descending order of degree values.