ABSTRACT
Aim To explore the active compound of Maxingganshi decoction in treatment of novel coronavirus pneumonia(COVID-19). Methods With the help of TCMSP database, the chemical components and action targets of ephedra, almond, licorice, and gypsum in Maxingganshi decoction were searched, and then a C-T network, protein interaction analysis, GO functional enrichment analysis, and KEGG pathway enrichment were constructed. Analysis was performed to predict its mechanism of action. Results A total of 120 compounds in Maxingganshi decoction corresponded to 222 targets. PTGS2, ESR1, PPARG, AR, NOS2, NCOA2 acted on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, T cell receptor signaling pathways, etc. The results of molecular docking showed that the affinity of quercetin, kaempferol, glabridin and other core compounds was similar to recommended drugs in treatment of COVID-19. Conclusions The active compounds of Maxingganshi decoction can target multiple pathways to achieve the therapeutic effect of COVID-19.Copyright © 2020 Publication Centre of Anhui Medical University. All rights reserved.
ABSTRACT
CASE: Patient is a 63 y/o F with PMH of relapsed AML on treatment with Gilteritinib, Meniere's Disease, asthma, GERD, PRA positive, CKD Stage 3. She was on cycle 1 day + 20 of Gilteritinib when she presented with a neutropenic fever of 101.9. She reported congestion and headache. She was pan cultured and started on empiric Cefepime. Her blood cultures, COVID test and CXR were all negative for sources of infection. Eventually, Cefepime was stopped, and she was transited to PO Cefdinir and Cipro but redeveloped fevers and a maculopapular rash. Repeat pan-cultures were negative. Antibiotics were broadened to Merrem, Linezolid and Cresemba and her fevers improved. However, the rash continued to worsen. There was concern that nodular rash was secondary to infection or possible drug reaction from her antibiotics. Her rash showed no improvement with Benadryl or withholding drugs. She underwent skin punch biopsy before discharge. Biopsy showed florid superficial inflammation with benign ulcer that was highly suggestive of Sweet Syndrome given history of AML. IMPACT/DISCUSSION: Sweet syndrome (SS), or acute febrile neutrophilic dermatosis is a rare inflammatory condition characterized by painful cutaneous nodules and neutrophilic infiltrate in the dermis, in the absence of vasculitis. This syndrome is associated with malignancies with AML and MDS being the most reported. Malignancy associated Sweet Syndrome accounts for 15-20% of cases of SS. The atypical production of both pro-inflammatory cytokines (IL - 6, TNF - alpha) and signaling molecules demonstrated in AML is suspected to affect neutrophil function leasing to dermal clumping of the mature neutrophils. In our patient the fever presented prior to the rash with sudden onset of nodular as it has been commonly reported in literature review. Glucocorticoids, either topical or systemic, together with antibiotics and wound care, represent the mainstays of SS therapy. The rash heals without scarring if no ulcerations are present. The signs and symptoms of Sweet syndrome can mimic infection and be treated inaccurately, thus, it is important to make a correct diagnosis. Our patient's tissue cultures were negative for microorganisms. She was started on glucocorticoid with good response in regards to her rash but did have some scars and hyperpigmentation. Unfortunately due to her aggressive AML and complications patient elected to go to Hospice. CONCLUSION: When SS is established, the physician should keep a high index of suspicion to search underlying malignancies. Sweet Syndrome generally responds promptly to treatment with glucocorticoid.
ABSTRACT
Aim To explore the active compound of Maxingganshi decoction in treatment of novel coronavirus pneumonia(COVID-19). Methods With the help of TCMSP database, the chemical components and action targets of ephedra, almond, licorice, and gypsum in Maxingganshi decoction were searched, and then a C-T network, protein interaction analysis, GO functional enrichment analysis, and KEGG pathway enrichment were constructed. Analysis was performed to predict its mechanism of action. Results A total of 120 compounds in Maxingganshi decoction corresponded to 222 targets. PTGS2, ESR1, PPARG, AR, NOS2, NCOA2 acted on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, T cell receptor signaling pathways, etc. The results of molecular docking showed that the affinity of quercetin, kaempferol, glabridin and other core compounds was similar to recommended drugs in treatment of COVID-19. Conclusions The active compounds of Maxingganshi decoction can target multiple pathways to achieve the therapeutic effect of COVID-19.
ABSTRACT
BACKGROUND: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the coronavirus disease of 2019 (COVID-19) that killed more than 3.5 million people till now. The cytokine storm induced in severe COVID-19 patients causes hyper-inflammation, is the primary reason for respiratory and multi-organ failure and fatality. This work uses a rational computational strategy to identify the existing drug molecules to target host pathways to reduce the cytokine storm. RESULTS: We used a "host response signature network" consist of 36 genes induced by SARS-CoV-2 infection and associated with cytokine storm. In order to attenuate the cytokine storm, potential drug molecules were searched against "host response signature network". Our study identified that drug molecule andrographolide, naturally present in a medicinal plant Andrographis paniculata, has the potential to bind with crucial proteins to block the TNF-induced NFkB1 signaling pathway responsible for cytokine storm in COVID-19 patients. The molecular docking method showed the binding of andrographolide with TNF and covalent binding with NFkB1 proteins of the TNF signaling pathway. CONCLUSION: We used a rational computational approach to repurpose existing drugs targeting host immunomodulating pathways. Our study suggests that andrographolide could bind with TNF and NFkB1 proteins, block TNF-induced cytokine storm in COVID-19 patients, and warrant further experimental validation.