Harnessing phytoconstituents to treat COVID-19 triggered acute respiratory distress syndrome: Insights from network pharmacology, and molecular modeling

Gupta et al., Phytochemistry Letters, doi:10.1016/j.phytol.2025.104105, Jan 2026
Quercetin for COVID-19
26th treatment shown to reduce risk in July 2021, now with p = 0.002 from 12 studies.
Lower risk for ICU, hospitalization, recovery, cases, and viral clearance.
No treatment is 100% effective. Protocols combine treatments.
6,300+ studies for 210+ treatments. c19early.org
Meta Analysis
In silico study showing that phytoconstituents apigenin-7-glucoside and quercetin bind strongly to inflammatory targets EGFR, JAK2, and RELA associated with COVID-19-triggered acute respiratory distress syndrome (ARDS).
90 preclinical studies support the efficacy of quercetin for COVID-19:
54 in silico studies1-54
30 in vitro studies2,3,5,6,8-10,13,23,28,30,34,51,55-71
6 in vivo animal studies13,28,63,66,72,73
In silico studies predict inhibition of SARS-CoV-2, or minimization of side effects, with quercetin or metabolites via binding to the spikeA,10,11,17,18,31,33,34,36,39,47,48,50,51,74 (and specifically the receptor binding domainB,7), MproC,6,7,10,11,15,17,19,21,23,25,27,29,32,33,36,39,43,45-47,51-54,71, RNA-dependent RNA polymeraseD,7,9-11,17,41, PLproE,11,46,54, ACE2F,26,31,32,36,37,46,50, TMPRSS2G,31, nucleocapsidH,11, helicaseI,11,38,43, endoribonucleaseJ,48, NSP16/10K,14, cathepsin LL,35, Wnt-3M,31, FZDN,31, LRP6O,31, ezrinP,49, ADRPQ,47, NRP1R,50, EP300S,24, PTGS2T,32, HSP90AA1U,24,32, matrix metalloproteinase 9V,40, IL-6W,30,44, IL-10X,30, VEGFAY,44, and RELAZ,44 proteins, and inhibition of spike-ACE2 interactionAA,8. In vitro studies demonstrate inhibition of the MproC,23,57,62,70 protein, and inhibition of spike-ACE2 interactionAA,58. In vitro studies demonstrate efficacy in Calu-3AB,61, A549AC,30, HEK293-ACE2+AD,69, Huh-7AE,34, Caco-2AF,60, Vero E6AG,28,51,60, mTECAH,63, RAW264.7AI,63, and HLMECAJ,8 cells. Animal studies demonstrate efficacy in K18-hACE2 miceAK,66, db/db miceAL,63,73, BALB/c miceAM,72, and rats28. Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice72, inhibits LPS-induced cytokine storm by modulating key inflammatory and antioxidant pathways in macrophages13, may block ACE2-spike interaction and NLRP3 inflammasome, limiting viral entry and inflammation4, upregulates the SIRT1/AMPK axis to inhibit oxidative injury and accelerate viral clearance75, inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity65, and may alleviate COVID-19 ARDS via inhibition of EGFR and JAK2 inflammatory targets1.
Important missing comments or errors? Let us know.
a. The trimeric spike (S) protein is a glycoprotein that mediates viral entry by binding to the host ACE2 receptor, is critical for SARS-CoV-2's ability to infect host cells, and is a target of neutralizing antibodies. Inhibition of the spike protein prevents viral attachment, halting infection at the earliest stage.
b. The receptor binding domain is a specific region of the spike protein that binds ACE2 and is a major target of neutralizing antibodies. Focusing on the precise binding site allows highly specific disruption of viral attachment with reduced potential for off-target effects.
c. The main protease or Mpro, also known as 3CLpro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting Mpro disrupts the SARS-CoV-2 lifecycle within the host cell, preventing the creation of new copies.
d. RNA-dependent RNA polymerase (RdRp), also called nsp12, is the core enzyme of the viral replicase-transcriptase complex that copies the positive-sense viral RNA genome into negative-sense templates for progeny RNA synthesis. Inhibiting RdRp blocks viral genome replication and transcription.
e. The papain-like protease (PLpro) has multiple functions including cleaving viral polyproteins and suppressing the host immune response by deubiquitination and deISGylation of host proteins. Inhibiting PLpro may block viral replication and help restore normal immune responses.
f. The angiotensin converting enzyme 2 (ACE2) protein is a host cell transmembrane protein that serves as the cellular receptor for the SARS-CoV-2 spike protein. ACE2 is expressed on many cell types, including epithelial cells in the lungs, and allows the virus to enter and infect host cells. Inhibition may affect ACE2's physiological function in blood pressure control.
g. Transmembrane protease serine 2 (TMPRSS2) is a host cell protease that primes the spike protein, facilitating cellular entry. TMPRSS2 activity helps enable cleavage of the spike protein required for membrane fusion and virus entry. Inhibition may especially protect respiratory epithelial cells, buy may have physiological effects.
h. The nucleocapsid (N) protein binds and encapsulates the viral genome by coating the viral RNA. N enables formation and release of infectious virions and plays additional roles in viral replication and pathogenesis. N is also an immunodominant antigen used in diagnostic assays.
i. The helicase, or nsp13, protein unwinds the double-stranded viral RNA, a crucial step in replication and transcription. Inhibition may prevent viral genome replication and the creation of new virus components.
j. The endoribonuclease, also known as NendoU or nsp15, cleaves specific sequences in viral RNA which may help the virus evade detection by the host immune system. Inhibition may hinder the virus's ability to mask itself from the immune system, facilitating a stronger immune response.
k. The NSP16/10 complex consists of non-structural proteins 16 and 10, forming a 2'-O-methyltransferase that modifies the viral RNA cap structure. This modification helps the virus evade host immune detection by mimicking host mRNA, making NSP16/10 a promising antiviral target.
l. Cathepsin L is a host lysosomal cysteine protease that can prime the spike protein through an alternative pathway when TMPRSS2 is unavailable. Dual targeting of cathepsin L and TMPRSS2 may maximize disruption of alternative pathways for virus entry.
m. Wingless-related integration site (Wnt) ligand 3 is a host signaling molecule that activates the Wnt signaling pathway, which is important in development, cell growth, and tissue repair. Some studies suggest that SARS-CoV-2 infection may interfere with the Wnt signaling pathway, and that Wnt3a is involved in SARS-CoV-2 entry.
n. The frizzled (FZD) receptor is a host transmembrane receptor that binds Wnt ligands, initiating the Wnt signaling cascade. FZD serves as a co-receptor, along with ACE2, in some proposed mechanisms of SARS-CoV-2 infection. The virus may take advantage of this pathway as an alternative entry route.
o. Low-density lipoprotein receptor-related protein 6 is a cell surface co-receptor essential for Wnt signaling. LRP6 acts in tandem with FZD for signal transduction and has been discussed as a potential co-receptor for SARS-CoV-2 entry.
p. The ezrin protein links the cell membrane to the cytoskeleton (the cell's internal support structure) and plays a role in cell shape, movement, adhesion, and signaling. Drugs that occupy the same spot on ezrin where the viral spike protein would bind may hindering viral attachment, and drug binding could further stabilize ezrin, strengthening its potential natural capacity to impede viral fusion and entry.
q. The Adipocyte Differentiation-Related Protein (ADRP, also known as Perilipin 2 or PLIN2) is a lipid droplet protein regulating the storage and breakdown of fats in cells. SARS-CoV-2 may hijack the lipid handling machinery of host cells and ADRP may play a role in this process. Disrupting ADRP's interaction with the virus may hinder the virus's ability to use lipids for replication and assembly.
r. Neuropilin-1 (NRP1) is a cell surface receptor with roles in blood vessel development, nerve cell guidance, and immune responses. NRP1 may function as a co-receptor for SARS-CoV-2, facilitating viral entry into cells. Blocking NRP1 may disrupt an alternative route of viral entry.
s. EP300 (E1A Binding Protein P300) is a transcriptional coactivator involved in several cellular processes, including growth, differentiation, and apoptosis, through its acetyltransferase activity that modifies histones and non-histone proteins. EP300 facilitates viral entry into cells and upregulates inflammatory cytokine production.
t. Prostaglandin G/H synthase 2 (PTGS2, also known as COX-2) is an enzyme crucial for the production of inflammatory molecules called prostaglandins. PTGS2 plays a role in the inflammatory response that can become severe in COVID-19 and inhibitors (like some NSAIDs) may have benefits in dampening harmful inflammation, but note that prostaglandins have diverse physiological functions.
u. Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) is a chaperone protein that helps other proteins fold correctly and maintains their stability. HSP90AA1 plays roles in cell signaling, survival, and immune responses. HSP90AA1 may interact with numerous viral proteins, but note that it has diverse physiological functions.
v. Matrix metalloproteinase 9 (MMP9), also called gelatinase B, is a zinc-dependent enzyme that breaks down collagen and other components of the extracellular matrix. MMP9 levels increase in severe COVID-19. Overactive MMP9 can damage lung tissue and worsen inflammation. Inhibition of MMP9 may prevent excessive tissue damage and help regulate the inflammatory response.
w. The interleukin-6 (IL-6) pro-inflammatory cytokine (signaling molecule) has a complex role in the immune response and may trigger and perpetuate inflammation. Elevated IL-6 levels are associated with severe COVID-19 cases and cytokine storm. Anti-IL-6 therapies may be beneficial in reducing excessive inflammation in severe COVID-19 cases.
x. The interleukin-10 (IL-10) anti-inflammatory cytokine helps regulate and dampen immune responses, preventing excessive inflammation. IL-10 levels can also be elevated in severe COVID-19. IL-10 could either help control harmful inflammation or potentially contribute to immune suppression.
y. Vascular Endothelial Growth Factor A (VEGFA) promotes the growth of new blood vessels (angiogenesis) and has roles in inflammation and immune responses. VEGFA may contribute to blood vessel leakiness and excessive inflammation associated with severe COVID-19.
z. RELA is a transcription factor subunit of NF-kB and is a key regulator of inflammation, driving pro-inflammatory gene expression. SARS-CoV-2 may hijack and modulate NF-kB pathways.
aa. The interaction between the SARS-CoV-2 spike protein and the human ACE2 receptor is a primary method of viral entry, inhibiting this interaction can prevent the virus from attaching to and entering host cells, halting infection at an early stage.
ab. Calu-3 is a human lung adenocarcinoma cell line with moderate ACE2 and TMPRSS2 expression and SARS-CoV-2 susceptibility. It provides a model of the human respiratory epithelium, but many not be ideal for modeling early stages of infection due to the moderate expression levels of ACE2 and TMPRSS2.
ac. A549 is a human lung carcinoma cell line with low ACE2 expression and SARS-CoV-2 susceptibility. Viral entry/replication can be studied but the cells may not replicate all aspects of lung infection.
ad. HEK293-ACE2+ is a human embryonic kidney cell line engineered for high ACE2 expression and SARS-CoV-2 susceptibility.
ae. Huh-7 cells were derived from a liver tumor (hepatoma).
af. Caco-2 cells come from a colorectal adenocarcinoma (cancer). They are valued for their ability to form a polarized cell layer with properties similar to the intestinal lining.
ag. Vero E6 is an African green monkey kidney cell line with low/no ACE2 expression and high SARS-CoV-2 susceptibility. The cell line is easy to maintain and supports robust viral replication, however the monkey origin may not accurately represent human responses.
ah. mTEC is a mouse tubular epithelial cell line.
ai. RAW264.7 is a mouse macrophage cell line.
aj. HLMEC (Human Lung Microvascular Endothelial Cells) are primary endothelial cells derived from the lung microvasculature. They are used to study endothelial function, inflammation, and viral interactions, particularly in the context of lung infections such as SARS-CoV-2. HLMEC express ACE2 and are susceptible to SARS-CoV-2 infection, making them a relevant model for studying viral entry and endothelial responses in the lung.
ak. A mouse model expressing the human ACE2 receptor under the control of the K18 promoter.
al. A mouse model of obesity and severe insulin resistance leading to type 2 diabetes due to a mutation in the leptin receptor gene that impairs satiety signaling.
am. A mouse model commonly used in infectious disease and cancer research due to higher immune response and susceptibility to infection.
Gupta et al., 14 Jan 2026, India, peer-reviewed, 4 authors. Contact: gurjotkaurbains@yahoo.co.in.
In silico studies are an important part of preclinical research, however results may be very different in vivo.
Harnessing phytoconstituents to treat COVID-19 triggered acute respiratory distress syndrome: Insights from network pharmacology, and molecular modeling
Pragati Gupta, Kamal Dev, Chirag N Patel, Gurjot Kaur
Phytochemistry Letters, doi:10.1016/j.phytol.2025.104105
Developing effective therapies for COVID-19-triggered acute respiratory distress syndrome (ARDS) remains a major challenge. Inflammatory signaling molecules have emerged as promising druggable targets. This study employed an integrated network pharmacology and molecular modeling strategy to investigate the antiinflammatory phytoconstituents (PCs) against COVID-19-triggered ARDS. Putative targets of PCs and disease genes were retrieved from multiple databases, followed by PPI and enrichment analyses, along with network visualization. Network pharmacology identified key phytoconstituents: 1-dehydro-6-gingerol, apigenin-7glucoside, and quercetin, and crucial targets including EGFR, JAK2, RELA, HSP90AA1, and PIK3CA from the F-B-PCs-T-P network. Enriched inflammatory pathways included Toll-like receptor, PI3K-Akt, NOD-like receptor, and HIF-1 signaling. Molecular docking and dynamics simulations further confirmed stable, high-affinity interactions between these targets and selected PCs. Specifically, apigenin-7-glucoside showed strong binding with JAK2 and RELA, while quercetin favoured JAK2 and EGFR. Overall, the findings underscore the therapeutic potential of these PCs and validate integrated in silico approaches (in) drug discovery.
Author contribution GK and PG conceptualized the study. PG conducted network pharmacology and molecular docking and interpreted molecular dynamics results. CP performed molecular dynamics and contributed to its writing. PG collected all results and analyzed them with the help of GK. KD gave guidance through extensive comments. PG wrote the first draft and GK contributed to manuscript finalization through extensive editing of the text, figures, and tables. CRediT authorship contribution statement Supplementary data Supplementary tables and figures related to this study can be found in the Supplementary Data doc file. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Appendix A. Supporting information Supplementary data associated with this article can be found in the online version at doi:10.1016/j.phytol.2025.104105.
References
Alfaro, Díaz-García, García-Tovar, Galera, Casitas et al., Endothelial dysfunction and persistent inflammation in severe post-COVID-19 patients: implications for gas exchange, BMC Med, doi:10.1186/s12916-024-03461-5
Assenov, Ramírez, Schelhorn, Lengauer, Albrecht, Computing topological parameters of biological networks, Bioinformatics, doi:10.1093/bioinformatics/btm554
Basile, Cavalli, Mccubrey, Hernández-Bello, Muñoz-Valle et al., The PI3K/Akt/mTOR pathway: a potential pharmacological target in COVID-19, Drug Discov. Today, doi:10.1016/j.drudis.2021.11.002
Batra, Whalen, Alvarez-Mulett, Gomez-Escobar, Hoffman et al., Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS, PLoS Pathog, doi:10.1371/journal.ppat.1010819
Bombicz, Priksz, Varga, Kurucz, Kertész et al., A novel therapeutic approach in the treatment of pulmonary arterial hypertension: Allium ursinum liophylisate alleviates symptoms comparably to sildenafil, Int. J. Mol. Sci, doi:10.3390/ijms18071436
Brault, Zerbib, Kontar, Fouquet, Carpentier et al., COVID-19-versus non-COVID-19-related acute respiratory distress syndrome: differences and similarities, Am. J. Respir. Crit. Care Med, doi:10.1164/rccm.202005-2025LE
Chandran, Mehendale, Tillu, Patwardhan, Network pharmacology: an emerging technique for natural product drug discovery and scientific research on Ayurveda, Proc. Indian Natl. Sci. Acad, doi:10.16943/ptinsa/2015/v81i3/48229
Choudhary, Thrigulla, Gundeti, Mantena, Koulgi et al., Balchaturbhadra Churna as a potential medicine for SARS-CoV2 infection in pediatric setting, AYU, doi:10.4103/ayu.ayu_255_22
Das, Singh, Ameeruddin, Bindhani, Obaidullah et al., Ethnomedicinal values of Boerhaavia diffusa L. as a panacea against multiple human ailments: a state of art review, Front. Chem, doi:10.3389/fchem.2023.1297300
Divya, Reeda, Rajkumar, Ranchani, Shahidha et al., Structural insights and ADMET analysis of CAFI: hydrogen bonding, molecular docking, and drug-likeness in renal function enhancers, BMC Chem, doi:10.1186/s13065-025-01383-8
Fuchs, Milbradt, Skin anti-inflammatory activity of Apigenin-7-glucoside in rats, Arzneim. Forsch
Gao, Li, Huang, Deiuliis, Braunstein et al., Deciphering the therapeutic potential of Myeloid-Specific JAK2 inhibition in acute respiratory distress syndrome, Mucosal Immunol, doi:10.1016/j.mucimm.2024.08.008
Garvin, Alvarez, Miller, Prates, Walker et al., A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm, eLife, doi:10.7554/eLife.59177
Girija, Sivan, Ayurvedic treatment of COVID-19/SARS-CoV-2: a case report, J. Ayurveda Integr. Med, doi:10.1016/j.jaim.2020.06.001
Gupta, Kaushik, Chauhan, Ahirwar, Sharma et al., Antimycobacterial activity of some medicinal plants used traditionally by tribes from P. Gupta et al. Phytochemistry Letters, J. Ethnopharmacol, doi:10.1016/j.jep.2018.08.031
Halgren, Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94, J. Comput. Chem
Han, Kim, Park, Hwang, Park et al., Reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection by blocking the epidermal growth factor receptor (EGFR) pathway, Microbiol. Spectr, doi:10.1128/spectrum.01583-24
Hu, Li, Fu, Zhao, Wang, The JAK/STAT signaling pathway: from bench to clinic, Signal Transduct. Target. Ther, doi:10.1038/s41392-021-00791-1
Jiang, Zhao, Zhou, Xiang, Gutierrez-Castrellon et al., Inflammatory pathways in COVID-19: mechanism and therapeutic interventions, MedComm, doi:10.1002/mco2.154
Jorgensen, Chandrasekhar, Madura, Impey, Klein, Comparison of simple potential functions for simulating liquid water, J. Chem. Phys, doi:10.1063/1.445869
Jorgensen, Maxwell, Tirado-Rives, Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids, J. Am. Chem. Soc
Kaminski, Friesner, Tirado-Rives, Jorgensen, Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides, J. Phys. Chem, doi:10.1021/jp003919d
Kollman, Massova, Reyes, Kuhn, Huo et al., Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models, Acc. Chem. Res, doi:10.1021/ar000033j
Kumar, Selvaraj, Vickram, Jenifer, Karthik Raja, Experimental and theoretical investigations on antiproliferative compound nootkatone's vibrational characteristics, solvent effects of electronic properties, topological insights, Hirshfeld surface, donor-acceptor insights, ADME, and molecular docking against SMAD proteins, J. Mol. Struct, doi:10.1016/j.molstruc.2025.143156
Lai, Killingsworth, Lee, Gene of the month: PIK3CA, J. Clin. Pathol, doi:10.1136/jclinpath-2015-202885
Li, Li, Wang, Yang, Huang et al., SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K/AKT/mTOR signaling, Biochim. Et. Biophys. Acta Mol. Basis Dis, doi:10.1016/j.bbadis.2021.166260
Lipinski, Lombardo, Dominy, Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Deliv. Rev, doi:10.1016/s0169-409x(00)00129-0
Matthay, Zemans, Zimmerman, Arabi, Beitler et al., Acute respiratory distress syndrome, Nat. Rev. Dis. Prim, doi:10.1038/s41572-019-0069-0
Mcgill, Markoutsa, Mayilsamy, Green, Sivakumar et al., Acetate-encapsulated Linolenic Acid Liposomes Reduce SARS-CoV-2 and RSV Infection, Viruses, doi:10.3390/v15071429
Meyer, Gattinoni, Calfee, Acute respiratory distress syndrome, Lancet, doi:10.1016/S0140-6736(21)00439-6
Mirza, Mahmood, Hilles, Ali, Khan et al., Quercetin as a therapeutic product: evaluation of its pharmacological action and clinical applications-a review, Pharmaceuticals, doi:10.3390/ph16111631
Mohammed, Fighting cytokine storm and immunomodulatory deficiency: by using natural products therapy up to now, Front. Pharmacol, doi:10.3389/fphar.2023.1111329
Morris, Ruth, Lindstrom, Sanner, Belew et al., Software news and updates AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility, J. Comput. Chem, doi:10.1002/jcc.21256
Nilsson-Payant, Uhl, Grimont, Doane, Cohen et al., The NF-κB transcriptional footprint is essential for SARS-CoV-2 replication, J. Virol, doi:10.1128/jvi.01257-21
Palakkott, Alneyadi, Muhammad, Eid, Amiri et al., The SARS-CoV-2 spike protein activates the epidermal growth factor receptor-mediated signaling, Vaccines, doi:10.3390/vaccines11040768
Panahi, Gorabi, Talaei, Beiraghdar, Akbarzadeh et al., An overview on the treatments and prevention against COVID-19, Virol. J, doi:10.1186/s12985-023-01973-9
Panda, Doddanagali, Clinical efficacy of herbal Padmapatradi yoga in bronchial asthma (Tamaka Swasa), J. Ayurveda Integr. Med, doi:10.4103/0975-9476.82522
Patel, Acharya, Acharya, Clerodendrum serratum (L.) Moon. A review on traditional uses, phytochemistry and pharmacological activities, J. Ethnopharmacol, doi:10.1016/j.jep.2014.03.071
Ramji Husayn, Christopher, Anderson, Greer, Zoe et al., Management of the hospitalized patient with COVID-Part One, J. Okla. State Med. Assoc
Rauf, Uddin, Latif, Muhammad, Pistagremic acid, a novel antimicrobial and antioxidant isolated from pistacia integerrima, Chem. Nat. Compd, doi:10.1007/s10600-014-0875-2
Selickman, Vrettou, Mentzelopoulos, Marini, COVID-19-Related ARDS: key mechanistic features and treatments, J. Clin. Med, doi:10.3390/jcm11164896
Serdaroglu, Uludag, Colak, Rajkumar, Nitrobenzamido substitution on thiophene-3-carboxylate: electrochemical investigation, antioxidant activity, molecular docking, DFT calculations, J. Mol. Struct, doi:10.1016/j.molstruc.2022.134030
Shannon, Markiel, Ozier, Baliga, Wang et al., Cytoscape: a software Environment for integrated models of biomolecular interaction networks, Genome Res, doi:10.1101/gr.1239303
Sjoding, Admon, Saha, Kay, Brown et al., Comparing clinical features and outcomes in mechanically ventilated patients with COVID-19 and acute respiratory distress syndrome, Ann. Am. Thorac. Soc, doi:10.1513/AnnalsATS.202008-1076OC
Sriramamoorthi, Gopal, Muralidar, Eswaran, Panneerselvam et al., Molecular basis of COVID-19, ARDS and COVID-19-associated ARDS: diagnosis pathogenesis and therapeutic strategies, Biocell, doi:10.32604/biocell.2023.029379
Taheri, Herrera-Bravo, Huala, Salazar, Sharifi-Rad et al., Cyperus spp.: a review on phytochemical composition, biological activity, and healthpromoting effects, Oxid. Med. Cell. Longev, doi:10.1155/2021/4014867
Tahoun, Sadaka, Deregulated expression of autophagy genes; PIK3C3 and RAB7A in COVID-19 patients, Hum. Immunol, doi:10.1016/j.humimm.2024.110801
Tzotzos, Fischer, Fischer, Zeitlinger, Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey, Crit. Care, doi:10.1186/s13054-020-03240-7
Uludag, Serdaroglu, Sugumar, Rajkumar, Colak et al., Synthesis of thiophene derivatives: substituent effect, antioxidant activity, cyclic voltammetry, molecular docking, DFT, and TD-DFT calculations, J. Mol. Struct, doi:10.1016/j.molstruc.2022.132607
Wang, Hou, Xu, Recent advances in free energy calculations with a combination of molecular mechanics and continuum models, Curr. Comput. Aided Drug Des
Welker, Huang, Gil, Ramakrishna, 2021 acute respiratory distress syndrome update, with coronavirus disease 2019 focus, J. Cardiothorac. Vasc. Anesth, doi:10.1053/j.jvca.2021.02.053
Wyler, Mösbauer, Franke, Diag, Gottula et al., Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy, iScience, doi:10.1016/j.isci.2021.102151
Zhao, Xu, Zhang, Liang, Jiao et al., Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis, J. Biol. Chem, doi:10.1016/j.jbc.2023.104668
Zheng, Sun, Xu, Gang, Song, Mechanisms of Apigenin-7glucoside As a Hepatoprotective Agent 1, Biomed. Environ. Sci
Zhou, Zhang, Dong, Wang, Zhang et al., The role of SARS-CoV-2-mediated NF-κB activation in COVID-19 patients, Hypertens. Res, doi:10.1038/s41440-023-01460-2
DOI record: { "DOI": "10.1016/j.phytol.2025.104105", "ISSN": [ "1874-3900" ], "URL": "http://dx.doi.org/10.1016/j.phytol.2025.104105", "alternative-id": [ "S1874390025021974" ], "article-number": "104105", "assertion": [ { "label": "This article is maintained by", "name": "publisher", "value": "Elsevier" }, { "label": "Article Title", "name": "articletitle", "value": "Harnessing phytoconstituents to treat COVID-19 triggered acute respiratory distress syndrome: Insights from network pharmacology, and molecular modeling" }, { "label": "Journal Title", "name": "journaltitle", "value": "Phytochemistry Letters" }, { "label": "CrossRef DOI link to publisher maintained version", "name": "articlelink", "value": "https://doi.org/10.1016/j.phytol.2025.104105" }, { "label": "Content Type", "name": "content_type", "value": "article" }, { "label": "Copyright", "name": "copyright", "value": "© 2026 Phytochemical Society of Europe. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies." } ], "author": [ { "affiliation": [], "family": "Gupta", "given": "Pragati", "sequence": "first" }, { "affiliation": [], "family": "Dev", "given": "Kamal", "sequence": "additional" }, { "affiliation": [], "family": "Patel", "given": "Chirag N.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-2894-4009", "affiliation": [], "authenticated-orcid": false, "family": "Kaur", "given": "Gurjot", "sequence": "additional" } ], "container-title": "Phytochemistry Letters", "container-title-short": "Phytochemistry Letters", "content-domain": { "crossmark-restriction": true, "domain": [ "elsevier.com", "sciencedirect.com" ] }, "created": { "date-parts": [ [ 2026, 1, 14 ] ], "date-time": "2026-01-14T04:01:47Z", "timestamp": 1768363307000 }, "deposited": { "date-parts": [ [ 2026, 1, 14 ] ], "date-time": "2026-01-14T08:18:07Z", "timestamp": 1768378687000 }, "indexed": { "date-parts": [ [ 2026, 1, 15 ] ], "date-time": "2026-01-15T14:37:37Z", "timestamp": 1768487857873, "version": "3.49.0" }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2026, 2 ] ] }, "language": "en", "license": [ { "URL": "https://www.elsevier.com/tdm/userlicense/1.0/", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 2, 1 ] ], "date-time": "2026-02-01T00:00:00Z", "timestamp": 1769904000000 } }, { "URL": "https://www.elsevier.com/legal/tdmrep-license", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 2, 1 ] ], "date-time": "2026-02-01T00:00:00Z", "timestamp": 1769904000000 } } ], "link": [ { "URL": "https://api.elsevier.com/content/article/PII:S1874390025021974?httpAccept=text/xml", "content-type": "text/xml", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://api.elsevier.com/content/article/PII:S1874390025021974?httpAccept=text/plain", "content-type": "text/plain", "content-version": "vor", "intended-application": "text-mining" } ], "member": "78", "original-title": [], "page": "104105", "prefix": "10.1016", "published": { "date-parts": [ [ 2026, 2 ] ] }, "published-print": { "date-parts": [ [ 2026, 2 ] ] }, "publisher": "Elsevier BV", "reference": [ { "DOI": "10.1186/s12916-024-03461-5", "article-title": "Endothelial dysfunction and persistent inflammation in severe post-COVID-19 patients: implications for gas exchange", "author": "Alfaro", "doi-asserted-by": "crossref", "first-page": "242", "issue": "1", "journal-title": "BMC Med.", "key": "10.1016/j.phytol.2025.104105_bib1", "volume": "22", "year": "2024" }, { "DOI": "10.1093/bioinformatics/btm554", "article-title": "Computing topological parameters of biological networks", "author": "Assenov", "doi-asserted-by": "crossref", "first-page": "282", "issue": "2", "journal-title": "Bioinformatics", "key": "10.1016/j.phytol.2025.104105_bib2", "volume": "24", "year": "2008" }, { "DOI": "10.1016/j.drudis.2021.11.002", "article-title": "The PI3K/Akt/mTOR pathway: a potential pharmacological target in COVID-19", "author": "Basile", "doi-asserted-by": "crossref", "first-page": "848", "issue": "3", "journal-title": "Drug Discov. Today", "key": "10.1016/j.phytol.2025.104105_bib3", "volume": "27", "year": "2022" }, { "DOI": "10.1371/journal.ppat.1010819", "article-title": "Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS", "author": "Batra", "doi-asserted-by": "crossref", "issue": "9", "journal-title": "PLoS Pathog.", "key": "10.1016/j.phytol.2025.104105_bib4", "volume": "18", "year": "2022" }, { "DOI": "10.3390/ijms18071436", "article-title": "A novel therapeutic approach in the treatment of pulmonary arterial hypertension: Allium ursinum liophylisate alleviates symptoms comparably to sildenafil", "author": "Bombicz", "doi-asserted-by": "crossref", "first-page": "1436", "issue": "7", "journal-title": "Int. J. Mol. Sci.", "key": "10.1016/j.phytol.2025.104105_bib5", "volume": "18", "year": "2017" }, { "DOI": "10.1164/rccm.202005-2025LE", "article-title": "COVID-19- versus non-COVID-19-related acute respiratory distress syndrome: differences and similarities", "author": "Brault", "doi-asserted-by": "crossref", "first-page": "1301", "issue": "9", "journal-title": "Am. J. Respir. Crit. Care Med.", "key": "10.1016/j.phytol.2025.104105_bib6", "volume": "202", "year": "2020" }, { "DOI": "10.16943/ptinsa/2015/v81i3/48229", "article-title": "Network pharmacology: an emerging technique for natural product drug discovery and scientific research on Ayurveda", "author": "Chandran", "doi-asserted-by": "crossref", "first-page": "561", "issue": "3", "journal-title": "Proc. Indian Natl. Sci. Acad.", "key": "10.1016/j.phytol.2025.104105_bib7", "volume": "81", "year": "2015" }, { "DOI": "10.4103/ayu.ayu_255_22", "article-title": "Balchaturbhadra Churna as a potential medicine for SARS-CoV2 infection in pediatric setting", "author": "Choudhary", "doi-asserted-by": "crossref", "first-page": "146", "issue": "4", "journal-title": "AYU", "key": "10.1016/j.phytol.2025.104105_bib8", "volume": "43", "year": "2022" }, { "DOI": "10.3389/fchem.2023.1297300", "article-title": "Ethnomedicinal values of Boerhaavia diffusa L. as a panacea against multiple human ailments: a state of art review", "author": "Das", "doi-asserted-by": "crossref", "journal-title": "Front. Chem.", "key": "10.1016/j.phytol.2025.104105_bib9", "volume": "11", "year": "2023" }, { "DOI": "10.1186/s13065-025-01383-8", "article-title": "Structural insights and ADMET analysis of CAFI: hydrogen bonding, molecular docking, and drug-likeness in renal function enhancers", "author": "Divya", "doi-asserted-by": "crossref", "issue": "1", "journal-title": "BMC Chem.", "key": "10.1016/j.phytol.2025.104105_bib10", "volume": "19", "year": "2025" }, { "article-title": "Skin anti-inflammatory activity of Apigenin-7-glucoside in rats", "author": "Fuchs", "first-page": "370", "issue": "3", "journal-title": "Arzneim. Forsch.", "key": "10.1016/j.phytol.2025.104105_bib11", "volume": "43", "year": "1993" }, { "DOI": "10.1016/j.mucimm.2024.08.008", "article-title": "Deciphering the therapeutic potential of Myeloid-Specific JAK2 inhibition in acute respiratory distress syndrome", "author": "Gao", "doi-asserted-by": "crossref", "journal-title": "Mucosal Immunol.", "key": "10.1016/j.phytol.2025.104105_bib12", "year": "2024" }, { "DOI": "10.7554/eLife.59177", "article-title": "A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm", "author": "Garvin", "doi-asserted-by": "crossref", "first-page": "1", "journal-title": "eLife", "key": "10.1016/j.phytol.2025.104105_bib13", "volume": "9", "year": "2020" }, { "DOI": "10.1016/j.jaim.2020.06.001", "article-title": "Ayurvedic treatment of COVID-19/SARS-CoV-2: a case report", "author": "Girija", "doi-asserted-by": "crossref", "issue": "1", "journal-title": "J. Ayurveda Integr. Med.", "key": "10.1016/j.phytol.2025.104105_bib14", "volume": "13", "year": "2022" }, { "DOI": "10.1016/j.jep.2018.08.031", "article-title": "Anti-mycobacterial activity of some medicinal plants used traditionally by tribes from Madhya Pradesh, India for treating tuberculosis related symptoms", "author": "Gupta", "doi-asserted-by": "crossref", "first-page": "113", "journal-title": "J. Ethnopharmacol.", "key": "10.1016/j.phytol.2025.104105_bib15", "volume": "227", "year": "2018" }, { "DOI": "10.1002/(SICI)1096-987X(199604)17:5/6<490::AID-JCC1>3.0.CO;2-P", "article-title": "Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94", "author": "Halgren", "doi-asserted-by": "crossref", "first-page": "490", "issue": "5–6", "journal-title": "J. Comput. Chem.", "key": "10.1016/j.phytol.2025.104105_bib16", "volume": "17", "year": "1996" }, { "DOI": "10.1128/spectrum.01583-24", "article-title": "Reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection by blocking the epidermal growth factor receptor (EGFR) pathway", "author": "Han", "doi-asserted-by": "crossref", "issue": "11", "journal-title": "Microbiol. Spectr.", "key": "10.1016/j.phytol.2025.104105_bib17", "volume": "12", "year": "2024" }, { "DOI": "10.1038/s41392-021-00791-1", "article-title": "The JAK/STAT signaling pathway: from bench to clinic", "author": "Hu", "doi-asserted-by": "crossref", "first-page": "402", "issue": "1", "journal-title": "Signal Transduct. Target. Ther.", "key": "10.1016/j.phytol.2025.104105_bib18", "volume": "6", "year": "2021" }, { "DOI": "10.1002/mco2.154", "article-title": "Inflammatory pathways in COVID-19: mechanism and therapeutic interventions", "author": "Jiang", "doi-asserted-by": "crossref", "issue": "3", "journal-title": "MedComm", "key": "10.1016/j.phytol.2025.104105_bib19", "volume": "3", "year": "2022" }, { "DOI": "10.1063/1.445869", "article-title": "Comparison of simple potential functions for simulating liquid water", "author": "Jorgensen", "doi-asserted-by": "crossref", "first-page": "926", "issue": "2", "journal-title": "J. Chem. Phys.", "key": "10.1016/j.phytol.2025.104105_bib20", "volume": "79", "year": "1983" }, { "DOI": "10.1021/ja9621760", "article-title": "Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids", "author": "Jorgensen", "doi-asserted-by": "crossref", "first-page": "11225", "issue": "45", "journal-title": "J. Am. Chem. Soc.", "key": "10.1016/j.phytol.2025.104105_bib21", "volume": "118", "year": "1996" }, { "DOI": "10.1021/jp003919d", "article-title": "Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides", "author": "Kaminski", "doi-asserted-by": "crossref", "first-page": "6474", "issue": "28", "journal-title": "J. Phys. Chem.", "key": "10.1016/j.phytol.2025.104105_bib22", "volume": "105", "year": "2001" }, { "DOI": "10.1021/ar000033j", "article-title": "Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models", "author": "Kollman", "doi-asserted-by": "crossref", "first-page": "889", "issue": "12", "journal-title": "Acc. Chem. Res.", "key": "10.1016/j.phytol.2025.104105_bib23", "volume": "33", "year": "2000" }, { "DOI": "10.1136/jclinpath-2015-202885", "article-title": "Gene of the month: PIK3CA", "author": "Lai", "doi-asserted-by": "crossref", "first-page": "253", "issue": "4", "journal-title": "J. Clin. Pathol.", "key": "10.1016/j.phytol.2025.104105_bib24", "volume": "68", "year": "2015" }, { "DOI": "10.1016/j.bbadis.2021.166260", "article-title": "SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K/AKT/mTOR signaling", "author": "Li", "doi-asserted-by": "crossref", "issue": "12", "journal-title": "Biochim. Et. Biophys. Acta Mol. Basis Dis.", "key": "10.1016/j.phytol.2025.104105_bib25", "volume": "1867", "year": "2021" }, { "DOI": "10.1016/S0169-409X(00)00129-0", "article-title": "Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings", "author": "Lipinski", "doi-asserted-by": "crossref", "first-page": "3", "issue": "1-3", "journal-title": "Adv. Drug Deliv. Rev.", "key": "10.1016/j.phytol.2025.104105_bib26", "volume": "46", "year": "2001" }, { "article-title": "Acute respiratory distress syndrome", "author": "Matthay", "issue": "1", "journal-title": "Nat. Rev. Dis. Prim.", "key": "10.1016/j.phytol.2025.104105_bib27", "volume": "5", "year": "2018" }, { "DOI": "10.3390/v15071429", "article-title": "Acetate-encapsulated Linolenic Acid Liposomes Reduce SARS-CoV-2 and RSV Infection", "author": "McGill", "doi-asserted-by": "crossref", "issue": "7", "journal-title": "Viruses", "key": "10.1016/j.phytol.2025.104105_bib28", "volume": "15", "year": "2023" }, { "DOI": "10.1016/S0140-6736(21)00439-6", "article-title": "Acute respiratory distress syndrome", "author": "Meyer", "doi-asserted-by": "crossref", "first-page": "622", "issue": "10300", "journal-title": "Lancet", "key": "10.1016/j.phytol.2025.104105_bib29", "volume": "398", "year": "2021" }, { "key": "10.1016/j.phytol.2025.104105_bib30", "unstructured": "Ministry of Health and Family Welfare, Govt. of India. The Ayurvedic Formulary of India. Part 1. 2nd revised ed. New Delhi: Department of Indian Systems of Medicine and Homeopathy, Ministry of Health and Family Welfare Govt. of India. (2003). 113." }, { "DOI": "10.3390/ph16111631", "article-title": "Quercetin as a therapeutic product: evaluation of its pharmacological action and clinical applications—a review", "author": "Mirza", "doi-asserted-by": "crossref", "issue": "11", "journal-title": "Pharmaceuticals", "key": "10.1016/j.phytol.2025.104105_bib31", "volume": "16", "year": "2023" }, { "DOI": "10.3389/fphar.2023.1111329", "article-title": "Fighting cytokine storm and immunomodulatory deficiency: by using natural products therapy up to now", "author": "Mohammed", "doi-asserted-by": "crossref", "journal-title": "Front. Pharmacol.", "key": "10.1016/j.phytol.2025.104105_bib32", "volume": "14", "year": "2023" }, { "DOI": "10.1002/jcc.21256", "article-title": "Software news and updates AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility", "author": "Morris", "doi-asserted-by": "crossref", "first-page": "2785", "issue": "16", "journal-title": "J. Comput. Chem.", "key": "10.1016/j.phytol.2025.104105_bib33", "volume": "30", "year": "2009" }, { "DOI": "10.1128/JVI.01257-21", "article-title": "The NF-κB transcriptional footprint is essential for SARS-CoV-2 replication", "author": "Nilsson-Payant", "doi-asserted-by": "crossref", "issue": "23", "journal-title": "J. Virol.", "key": "10.1016/j.phytol.2025.104105_bib34", "volume": "95", "year": "2021" }, { "DOI": "10.3390/vaccines11040768", "article-title": "The SARS-CoV-2 spike protein activates the epidermal growth factor receptor-mediated signaling", "author": "Palakkott", "doi-asserted-by": "crossref", "first-page": "768", "issue": "4", "journal-title": "Vaccines", "key": "10.1016/j.phytol.2025.104105_bib35", "volume": "11", "year": "2023" }, { "DOI": "10.1186/s12985-023-01973-9", "article-title": "An overview on the treatments and prevention against COVID-19", "author": "Panahi", "doi-asserted-by": "crossref", "first-page": "23", "issue": "1", "journal-title": "Virol. J.", "key": "10.1016/j.phytol.2025.104105_bib36", "volume": "20", "year": "2023" }, { "DOI": "10.4103/0975-9476.82522", "article-title": "Clinical efficacy of herbal Padmapatradi yoga in bronchial asthma (Tamaka Swasa)", "author": "Panda", "doi-asserted-by": "crossref", "first-page": "85", "issue": "2", "journal-title": "J. Ayurveda Integr. Med.", "key": "10.1016/j.phytol.2025.104105_bib37", "volume": "2", "year": "2011" }, { "DOI": "10.1016/j.jep.2014.03.071", "article-title": "Clerodendrum serratum (L.) Moon. A review on traditional uses, phytochemistry and pharmacological activities", "author": "Patel", "doi-asserted-by": "crossref", "first-page": "268", "issue": "2", "journal-title": "J. Ethnopharmacol.", "key": "10.1016/j.phytol.2025.104105_bib38", "volume": "154", "year": "2014" }, { "DOI": "10.1016/j.molstruc.2025.143156", "author": "Ram Kumar", "doi-asserted-by": "crossref", "journal-title": "J. Mol. Struct.", "key": "10.1016/j.phytol.2025.104105_bib39", "volume": "1346", "year": "2025" }, { "article-title": "Management of the hospitalized patient with COVID-Part One", "author": "Ramji Husayn", "issue": "1", "journal-title": "J. Okla. State Med. Assoc.", "key": "10.1016/j.phytol.2025.104105_bib40", "volume": "116", "year": "2022" }, { "DOI": "10.1007/s10600-014-0875-2", "article-title": "Pistagremic acid, a novel antimicrobial and antioxidant isolated from pistacia integerrima", "author": "Rauf", "doi-asserted-by": "crossref", "first-page": "97", "issue": "1", "journal-title": "Chem. Nat. Compd.", "key": "10.1016/j.phytol.2025.104105_bib41", "volume": "50", "year": "2014" }, { "DOI": "10.3390/jcm11164896", "article-title": "COVID-19-Related ARDS: key mechanistic features and treatments", "author": "Selickman", "doi-asserted-by": "crossref", "first-page": "4896", "issue": "16", "journal-title": "J. Clin. Med.", "key": "10.1016/j.phytol.2025.104105_bib42", "volume": "11", "year": "2022" }, { "DOI": "10.1016/j.molstruc.2022.134030", "article-title": "Nitrobenzamido substitution on thiophene-3-carboxylate: electrochemical investigation, antioxidant activity, molecular docking, DFT calculations", "author": "Serdaroğlu", "doi-asserted-by": "crossref", "journal-title": "J. Mol. Struct.", "key": "10.1016/j.phytol.2025.104105_bib43", "volume": "1271", "year": "2023" }, { "DOI": "10.1101/gr.1239303", "article-title": "Cytoscape: a software Environment for integrated models of biomolecular interaction networks", "author": "Shannon", "doi-asserted-by": "crossref", "first-page": "2498", "issue": "11", "journal-title": "Genome Res.", "key": "10.1016/j.phytol.2025.104105_bib44", "volume": "13", "year": "2003" }, { "DOI": "10.1513/AnnalsATS.202008-1076OC", "article-title": "Comparing clinical features and outcomes in mechanically ventilated patients with COVID-19 and acute respiratory distress syndrome", "author": "Sjoding", "doi-asserted-by": "crossref", "first-page": "1776", "issue": "11", "journal-title": "Ann. Am. Thorac. Soc.", "key": "10.1016/j.phytol.2025.104105_bib45", "volume": "18", "year": "2021" }, { "DOI": "10.32604/biocell.2023.029379", "article-title": "Molecular basis of COVID-19, ARDS and COVID-19-associated ARDS: diagnosis pathogenesis and therapeutic strategies", "author": "Sriramamoorthi", "doi-asserted-by": "crossref", "first-page": "2335", "issue": "11", "journal-title": "Biocell", "key": "10.1016/j.phytol.2025.104105_bib46", "volume": "47", "year": "2023" }, { "DOI": "10.1155/2021/4014867", "article-title": "Cyperus spp.: a review on phytochemical composition, biological activity, and health-promoting effects", "author": "Taheri", "doi-asserted-by": "crossref", "journal-title": "Oxid. Med. Cell. Longev.", "key": "10.1016/j.phytol.2025.104105_bib47", "volume": "2021", "year": "2021" }, { "DOI": "10.1016/j.humimm.2024.110801", "article-title": "Deregulated expression of autophagy genes; PIK3C3 and RAB7A in COVID-19 patients", "author": "Tahoun", "doi-asserted-by": "crossref", "issue": "3", "journal-title": "Hum. Immunol.", "key": "10.1016/j.phytol.2025.104105_bib48", "volume": "85", "year": "2024" }, { "DOI": "10.1186/s13054-020-03240-7", "article-title": "Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey", "author": "Tzotzos", "doi-asserted-by": "crossref", "first-page": "516", "issue": "1", "journal-title": "Crit. Care", "key": "10.1016/j.phytol.2025.104105_bib49", "volume": "24", "year": "2020" }, { "DOI": "10.1016/j.molstruc.2022.132607", "article-title": "Synthesis of thiophene derivatives: substituent effect, antioxidant activity, cyclic voltammetry, molecular docking, DFT, and TD-DFT calculations", "author": "Uludag", "doi-asserted-by": "crossref", "journal-title": "J. Mol. Struct.", "key": "10.1016/j.phytol.2025.104105_bib50", "volume": "1257", "year": "2022" }, { "DOI": "10.2174/157340906778226454", "article-title": "Recent advances in free energy calculations with a combination of molecular mechanics and continuum models", "author": "Wang", "doi-asserted-by": "crossref", "first-page": "287", "issue": "3", "journal-title": "Curr. Comput. Aided Drug Des.", "key": "10.1016/j.phytol.2025.104105_bib51", "volume": "2", "year": "2006" }, { "DOI": "10.1053/j.jvca.2021.02.053", "article-title": "2021 acute respiratory distress syndrome update, with coronavirus disease 2019 focus", "author": "Welker", "doi-asserted-by": "crossref", "first-page": "1188", "issue": "4", "journal-title": "J. Cardiothorac. Vasc. Anesth.", "key": "10.1016/j.phytol.2025.104105_bib52", "volume": "36", "year": "2022" }, { "DOI": "10.1016/j.isci.2021.102151", "article-title": "Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy", "author": "Wyler", "doi-asserted-by": "crossref", "issue": "3", "journal-title": "iScience", "key": "10.1016/j.phytol.2025.104105_bib53", "volume": "24", "year": "2021" }, { "DOI": "10.1016/j.jbc.2023.104668", "article-title": "Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis", "author": "Zhao", "doi-asserted-by": "crossref", "issue": "5", "journal-title": "J. Biol. Chem.", "key": "10.1016/j.phytol.2025.104105_bib54", "volume": "299", "year": "2023" }, { "article-title": "Mechanisms of Apigenin-7-glucoside As a Hepatoprotective Agent 1", "author": "Zheng", "journal-title": "Biomed. Environ. Sci.", "key": "10.1016/j.phytol.2025.104105_bib55", "volume": "18", "year": "2005" }, { "DOI": "10.1038/s41440-023-01460-2", "article-title": "The role of SARS-CoV-2-mediated NF-κB activation in COVID-19 patients", "author": "Zhou", "doi-asserted-by": "crossref", "first-page": "375", "issue": "2", "journal-title": "Hypertens. Res.", "key": "10.1016/j.phytol.2025.104105_bib56", "volume": "47", "year": "2024" } ], "reference-count": 56, "references-count": 56, "relation": {}, "resource": { "primary": { "URL": "https://linkinghub.elsevier.com/retrieve/pii/S1874390025021974" } }, "score": 1, "short-title": [], "source": "Crossref", "special_numbering": "C", "subject": [], "subtitle": [], "title": "Harnessing phytoconstituents to treat COVID-19 triggered acute respiratory distress syndrome: Insights from network pharmacology, and molecular modeling", "type": "journal-article", "update-policy": "https://doi.org/10.1016/elsevier_cm_policy", "volume": "71" }
Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.
  or use drag and drop   
Submit    
Post
Share
@CovidAnalysis
FAQ
Public domain CC0 1.0