Research & References

Dr. Daniel Weber,
DSc, PhD

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In recent studies, andrographolide [1], neoandrographolide [2], glycosides 5,4′-dihydroxy-7-O-β-D-pyran-glycuronate butyl ester and glycoside 3-O-β-D-glucopyranosyl-andrographolide [3] have been reported to have a potential role in inhibiting the main protease of SARS-CoV-2, including NSP9, RNA-dependent RNA polymerase, and 6LU7. Andrographolide was docked successfully in the binding site of SARS-CoV-2 Mpro. These findings revealed that the andrographolide molecule has good solubility, pharmacodynamics property and target accuracy [4]. In another very recent report also stated that andrographolide and its derivative-14-deoxy-11,12-didehydroandrographolide have strong binding affinities with targets. They can modulate the immune system by regulating chemokine signaling, Rap1 signaling, cytokine–cytokine receptor interaction, MAPK signaling, NF-kappa B signaling, RAS signaling, p53 signaling, HIF-1 signaling, and natural killer cell-mediated cytotoxicity [5]. A couple of in silico studies suggest strong interaction of andrographolide and its derivatives against COVID-19 associated target proteins and exhibited different immunoregulatory pathways. 

Another study demonstrated anti-SARS-CoV-2 activity of A. paniculata and andrographolide using a Calu-3- based anti-SARS-CoV-2 assay. Potent anti-SAR-CoV-2 activities, together with the favorable cytotoxicity profiles, and andrographolide exerted a stronger anti-SARS-CoV-2 effect than the whole extract [6]. Andrographis and andrographolide provides immune-protection and anti-viral response via involving different pathways, like toll-like receptor pathway, PI3/AKT pathway and MAP kinase pathways against COVID-19 infection. Andrographolide binds with TNF and NFkB1 proteins, to block TNF-induced cytokine storm in COVID-19 patients [8].

Conclusion: Andrographis paniculata extract and andrographolide have a potent anti-SARS-CoV-2 activity. Andrographolide possesses drug-like properties and could be a promising drug for further biochemical and cell-based experimental validation for combating severe COVID-19.

Figure. Potential SARS-CoV-2 antiviral target sites and mechanisms of actions predicted for andrographolide and its derivatives as indicated by the red boxes: (1) spike protein-ACE-2 complex, (2) spike protein, (3) host cell ACE-2 receptor, (4) PLpro, (5) 3CLpro, (6) RdRp, and (7) nucleotide protein binding domain. The diagram illustrates the overall suggested life cycle of SARS-CoV-2 infecting a human lung cell, including (A) attachment of viral spike protein to ACE-2 receptor, (B) viral membrane fusion via interaction with transmembrane serine protease 2 (TMPRSS2) receptor, (C) viral entry via internalization by host cell, (D) viral replication and transcription complex involving important proteins and enzymes such as RdRp, 3CLpro, PLpro, and nucleocapsid protein, (E) translocation of newly formed non-structural proteins, and (F) viral assembly and release to infect other cells [9].


NF- κ B and PI3K/AKT signaling. Andrographolide (Andro) inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF-κB and PI3K/AKT signaling in vitro and in vivo. Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice. The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo [10].

1. Screening of Kabasura Kudineer Chooranam against COVID-19 through Targeting of Main Protease and RNA-Dependent RNA Polymerase of SARS-Cov-2 by Molecular Docking Studies; SSRN: Rochester, NY, USA, 2020; 38p. 
2. Polypharmacology of Some Medicinal Plant Metabolites Against SARS-CoV-2 and Host Targets: Molecular Dynamics Evaluation of NSP9 RNA Binding Protein. ChemRxiv 2020. 
3. The corona virus disease 2019 main protease inhibitor from Andrographis paniculata (Burm. f) Ness. J. Adv. Pharm. Technol. Res. 2020, 11, 157–162.
4. Andrographolide as a potential inhibitor of SARS-CoV-2mainprotease:Anin silico approach. J. Biomol. Struct. Dyn. 2020, 1–7. 
5. Combination of system biology to probe the anti-viral activity of andrographolide and its derivative against COVID-19. RSC Adv. 2021, 11, 5065–5079. 
6. Anti-SARS-CoV-2 Activity of Andrographis paniculata Extract and Its Major Component Andrographolide in Human Lung Epithelial Cells and Cytotoxicity Evaluation in Major Organ Cell Representatives. J Nat Prod. 2021 Apr 23;84(4):1261-1270. doi: 10.1021/acs.jnatprod.0c01324.
7. Immunoprotective potential of Ayurvedic herb Kalmegh (Andrographis paniculata) against respiratory viral infections – LC-MS/MS and network pharmacology analysis. Phytochem Anal. 2021 Jul;32(4):629-639. doi: 10.1002/pca.3011.
8. A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm. Front. Immunol. 12:648250. doi: 10.3389/fimmu.2021.6482509. 
9. Andrographis paniculata (Burm. F.) Wall. Ex Nees, Andrographolide, and Andrographolide Analogues as SARS-CoV-2 Antivirals? A Rapid Review. Natural Product Communications. May 2021. doi:10.1177/1934578X211016610
10. Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF- κ B and PI3K/AKT Signaling In Vitro and In Vivo. Chin. J. Integr. Med. 28, 349–356 (2022).


The structural family of pentacyclic triterpenes, with high affinity values for viral protease, could be suggested as possible candidates for the treatment of COVID-19. Taraxasterol is a pentacyclic triterpene only found in a few plants like arnica, chicory, and dandelion, but with remarkably interesting biological activity [1].

In this workflow, we first short-listed 1672 plant-based phytochemicals through deep literature mining. The compounds were screened against the SARS-CoV-2 Mpro to identify potent inhibitors that might be able to interfere with the catalytic function of Mpro. The virtual screening and molecular docking studies identified three potent inhibitors: epicatechin-3-O-gallate, psi-taraxasterol, and catechin gallate from several large, compound data sets [2].

We found effective inhibition of protein-protein interaction between the human virus cell entry receptor ACE2 and SARS-CoV-2 spike, including five relevant mutations, by water-based common dandelion (Taraxacum officinale) extracts [3].

Antiviral activity. A study showed that aqueous Taraxacum officinale extract has antiviral activity in vitro, inhibiting human immunodeficiency virus type 1 (HIV-1) reverse transcription and replication. Another study found that this plant extract is able to prevent influenza infections by inhibiting virus replication. A recent study showed that Taraxacum officinale extract has antiviral activity in vitro against hepatitis B virus (HBV) and the bioactive compound which exerts this action is taraxasterol. Other studies found that this plant extract has antiviral activity against the dengue virus serotype 2 (DENV2) and the hepatitis C virus (HCV).

Effects on the immune system. Previous studies found that Taraxacum officinale extract improves immunity, increasing nitric oxide (NO) and cytokines production in mice. Another study showed that taraxasterol can activate the Bax/Bc1-2 anti-apoptotic signaling pathway, which is downregulated in autoimmune disorders. Lastly, a study found that Taraxacum officinale extracts ameliorate the immune response in vivo [4].

Conclusion: Taraxacum, containing Taraxasterol has shown biological activity against COVID-19, through its antiviral and immune system effects.


1. Virtual screening of plant-derived compounds against SARS-CoV-2 viral proteins using computational tools. Science of the Total Environment 781 (2021) 146400

2. Plant-Based Phytochemical Screening by Targeting Main Protease of SARS-CoV-2 to Design Effective Potent Inhibitors. Biology (Basel). 2021 Jun 26;10(7):589. doi: 10.3390/biology10070589.

3. Common dandelion (Taraxacum officinale) efficiently blocks the interaction between ACE2 cell surface receptor and SARS-CoV-2 spike protein D614, mutants D614G, N501Y, K417N and E484K in vitro. bioRxiv 2021.03.19.435959; doi:

4. A comprehensive review of the benefits of Taraxacum officinale on human health. Bull Natl Res Cent (2021) 45:110



Phenolic acids have recently gained substantial attention due to their various practical, biological and pharmacological effects. Chlorogenic Acid (CGA, 3-CQA) is a most abundant isomer among caffeoylquinic acid isomers (3-, 4-, and 5-CQA). CGA is an important and biologically active dietary polyphenol, playing several important and therapeutic roles such as antioxidant activity, antibacterial, hepatoprotective, cardioprotective, anti-inflammatory, antipyretic, neuroprotective, anti-obesity, antiviral, anti-microbial, anti-hypertension, free radicals scavenger and a central nervous system (CNS) stimulator [1].
CGA is a potential inhibitor of Coronavirus Disease 2019 (COVID-19). ACE2 and its co-expressed proteins are SARS-CoV-2 receptors, which have been linked to SARS-CoV-2 infection and considered as the key target of SARS-CoV-2 in entering target cells. CGA is an inhibitor of COVID-19: virtual screening experiment based on network pharmacology and molecular docking [2].
Conclusion: CGA had potential anti-SARS-CoV-2 activity via integrating three common receptors in clinical practice compared with clinical trial drugs registered for the treatment of COVID-19, as shown by molecular docking [3].

1. Chlorogenic acid (CGA): A pharmacological review and call for further research. Biomed Pharmacother. 2018 Jan;97:67-74. doi: 10.1016/j.biopha.2017.10.064.
2. Nat Prod Res. 2021 Mar 26:1-6. doi: 10.1080/14786419.2021.1904923.
3. Natural products may interfere with SARS-CoV-2 attachment to the host cell. Journal of Biomolecular Structure and Dynamics. Volume 39, 2021 – Issue 9


Andrographolide (Andro), the main active component of the herb Andrographis paniculata, has been used for many years to treat a variety of diseases including bacterial and viral infections. Andrographolide is an anti-pyretic, anti-inflammatory and immune enhancing compound. Its anti-inflammatory properties are due to the stimulation of adrenocortical hormone release and ACTH secretion.