Exploring the Potential of Siddha Formulation MilagaiKudineer-Derived Phytotherapeutics Against SARS-CoV-2: An In-Silico Investigation for Antiviral Intervention

Rajamanickam et al., Journal of Pharmacy and Pharmacology Research, doi:10.26502/fjppr.0105, Feb 2025

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https://c19early.org/rajamanickamt.html

Curcumin for COVID-19

15th treatment shown to reduce risk in February 2021, now with p = 0.0000000096 from 27 studies.

Lower risk for mortality, ventilation, hospitalization, progression, recovery, and viral clearance.

No treatment is 100% effective. Protocols combine treatments.

5,700+ studies for 169 treatments. c19early.org

In-Silico computational docking study of phytochemicals from MilagaiKudineer, showing potential inhibitory activity against SARS-CoV-2 targets. Authors evaluated binding affinities for the spike glycoprotein receptor-binding domain, RNA-dependent RNA polymerase, and the main protease (3CL^pro). Compounds including curcumin, quercetin, capsaicin, and dihydrocapsaicin demonstrated significant binding affinities, suggesting potential antiviral mechanisms through disruption of viral entry and replication. Vitamin C showed moderate affinity that may contribute synergistically in combination therapies.

55 preclinical studies support the efficacy of curcumin for COVID-19:

28 In Silico studies1-28

26 In Vitro studies1,3,5,9,11,15,21,25,29-46

1 In Vivo animal study9

In Silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spikeA,3,4,9,14,16,22,25 (and specifically the receptor binding domainB,2,12,15,18), M^proC,2-4,9,11,13-15,17,18,20,23,25,26,28,43, RNA-dependent RNA polymeraseD,2-4,15,24, PLproE,4, ACE2F,16,17,19, nucleocapsidG,10,27, nsp10H,27, and helicaseI,32 proteins, and inhibition of spike-ACE2 interactionJ,1. In Vitro studies demonstrate inhibition of the spikeA,37 (and specifically the receptor binding domainB,46), M^proC,21,37,43,45, ACE2F,46, and TMPRSS2K,46 proteins, and inhibition of spike-ACE2 interactionJ,1,30. In Vitro studies demonstrate efficacy in Calu-3L,44, A549M,37, 293TN,5, HEK293-hACE2O,21,35, 293T/hACE2/TMPRSS2P,36, Vero E6Q,11,15,25,35,37,39,40,42,44, and SH-SY5YR,34 cells. Curcumin is predicted to inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain and the human ACE2 receptor for the delta and omicron variants12, decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells42, alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress5, may limit COVID-19 induced cardiac damage by inhibiting the NF-κB signaling pathway which mediates the profibrotic effects of the SARS-CoV-2 spike protein on cardiac fibroblasts31, and inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity38.

Important missing comments or errors? Let us know.

Study covers quercetin, curcumin, and vitamin C.

1. Najimi et al., Phytochemical Inhibitors of SARS‐CoV‐2 Entry: Targeting the ACE2‐RBD Interaction with l‐Tartaric Acid, l‐Ascorbic Acid, and Curcuma longa Extract, ChemistrySelect, doi:10.1002/slct.202406035.wiley.com, doi.org.

2. Rajamanickam et al., Exploring the Potential of Siddha Formulation MilagaiKudineer-Derived Phytotherapeutics Against SARS-CoV-2: An In-Silico Investigation for Antiviral Intervention, Journal of Pharmacy and Pharmacology Research, doi:10.26502/fjppr.0105.fortunejournals.com, doi.org.

3. Al balawi et al., Assessing multi-target antiviral and antioxidant activities of natural compounds against SARS-CoV-2: an integrated in vitro and in silico study, Bioresources and Bioprocessing, doi:10.1186/s40643-024-00822-z.springeropen.com, doi.org.

4. Haque et al., Exploring potential therapeutic candidates against COVID-19: a molecular docking study, Discover Molecules, doi:10.1007/s44345-024-00005-5.springer.com, doi.org.

5. Zhang et al., Computational Discovery of Mitochondrial Dysfunction Biomarkers in Severe SARS-CoV-2 Infection: Facilitating Pytomedicine Screening, Phytomedicine, doi:10.1016/j.phymed.2024.155784.sciencedirect.com, doi.org.

6. Öztürkkan et al., In Silico investigation of the effects of curcuminoids on the spike protein of the omicron variant of SARS-CoV-2, Baku State University Journal of Chemistry and Material Sciences, 1:2, bsuj.bsu.edu.az/uploads/pdf/ec4204d62f7802de54e6092bf7860029.pdf.edu.az.

7. Yunze et al., Therapeutic effect and potential mechanism of curcumin, an active ingredient in Tongnao Decoction, on COVID-19 combined with stroke: a network pharmacology study and GEO database mining, Research Square, doi:10.21203/rs.3.rs-4329762/v1.researchsquare.com, doi.org.

8. Agamah et al., Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases, ScienceOpen, doi:10.58647/DRUGARXIV.PR000010.v1.scienceopen.com, doi.org.

9. Boseila et al., Throat spray formulated with virucidal Pharmaceutical excipients as an effective early prophylactic or treatment strategy against pharyngitis post-exposure to SARS CoV-2, European Journal of Pharmaceutics and Biopharmaceutics, doi:10.1016/j.ejpb.2024.114279.sciencedirect.com, doi.org.

10. Hidayah et al., Bioinformatics study of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin compounds in Curcuma longa as an antiviral agent via nucleocapsid on SARS-CoV-2 inhibition, International Conference on Organic and Applied Chemistry, doi:10.1063/5.0197724.aip.org, doi.org.

11. Singh et al., Unlocking the potential of phytochemicals in inhibiting SARS-CoV-2 M Pro protein - An in-silico and cell-based approach, Research Square, doi:10.21203/rs.3.rs-3888947/v1.researchsquare.com, doi.org.

12. Kant et al., Structure-based drug discovery to identify SARS-CoV2 spike protein–ACE2 interaction inhibitors, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2023.2300060.tandfonline.com, doi.org.

13. Naderi Beni et al., In silico studies of anti-oxidative and hot temperament-based phytochemicals as natural inhibitors of SARS-CoV-2 Mpro, PLOS ONE, doi:10.1371/journal.pone.0295014.plos.org, doi.org.

14. Moschovou et al., Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein, International Journal of Molecular Sciences, doi:10.3390/ijms242115894.mdpi.com, doi.org.

15. Eleraky et al., Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2, International Journal of Nanomedicine, doi:10.2147/IJN.S423251.dovepress.com, doi.org.

16. Singh (B) et al., Computational studies to analyze effect of curcumin inhibition on coronavirus D614G mutated spike protein, The Seybold Report, doi:10.17605/OSF.IO/TKEXJ.ac.in, doi.org.

17. Thapa et al., In-silico Approach for Predicting the Inhibitory Effect of Home Remedies on Severe Acute Respiratory Syndrome Coronavirus-2, Makara Journal of Science, doi:10.7454/mss.v27i3.1609.ac.id, doi.org.

18. Srivastava et al., Paradigm of Well-Orchestrated Pharmacokinetic Properties of Curcuminoids Relative to Conventional Drugs for the Inactivation of SARS-CoV-2 Receptors: An In Silico Approach, Stresses, doi:10.3390/stresses3030043.mdpi.com, doi.org.

19. Alkafaas et al., A study on the effect of natural products against the transmission of B.1.1.529 Omicron, Virology Journal, doi:10.1186/s12985-023-02160-6.biomedcentral.com, doi.org.

20. Winih Kinasih et al., Analisis in silico interaksi senyawa kurkuminoid terhadap enzim main protease 6LU7 dari SARS-CoV-2, Duta Pharma Journal, doi:10.47701/djp.v3i1.2904.ac.id, doi.org.

21. Wu et al., Potential Mechanism of Curcumin and Resveratrol against SARS-CoV-2, Research Square, doi:10.21203/rs.3.rs-2780614/v1.researchsquare.com, doi.org.

22. Nag et al., Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study, Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2022.105552.sciencedirect.com, doi.org.

23. Rampogu et al., Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2, International Journal of Molecular Sciences, doi:10.3390/ijms23031771.mdpi.com, doi.org.

24. Singh (C) et al., Potential of turmeric-derived compounds against RNA-dependent RNA polymerase of SARS-CoV-2: An in-silico approach, Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2021.104965.sciencedirect.com, doi.org.

25. Kandeil et al., Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2, Pathogens, doi:10.3390/pathogens10060758.mdpi.com, doi.org.

26. Rajagopal et al., Activity of phytochemical constituents of Curcuma longa (turmeric) and Andrographis paniculata against coronavirus (COVID-19): an in silico approach, Future Journal of Pharmaceutical Sciences, doi:10.1186/s43094-020-00126-x.springeropen.com, doi.org.

27. Suravajhala et al., Comparative Docking Studies on Curcumin with COVID-19 Proteins, Preprints, doi:10.20944/preprints202005.0439.v3.preprints.org, doi.org.

28. Sekiou et al., In-Silico Identification of Potent Inhibitors of COVID-19 Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from Natural Products: Quercetin, Hispidulin, and Cirsimaritin Exhibited Better Potential Inhibition than Hydroxy-Chloroquine Against COVID-19 Main Protease Active Site and ACE2, ChemRxiv, doi:10.26434/chemrxiv.12181404.v1.chemrxiv.org, doi.org.

29. Olubiyi et al., Novel dietary herbal preparations with inhibitory activities against multiple SARS-CoV-2 targets: A multidisciplinary investigation into antiviral activities, Food Chemistry Advances, doi:10.1016/j.focha.2025.100969.sciencedirect.com, doi.org.

30. Emam et al., Establishment of in-house assay for screening of anti-SARS-CoV-2 protein inhibitors, AMB Express, doi:10.1186/s13568-024-01739-8.springeropen.com, doi.org.

31. Van Tin et al., Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3 Inflammasomes and NF-κB Signaling, Cells, doi:10.3390/cells13161331.mdpi.com, doi.org.

32. Li et al., Thermal shift assay (TSA)-based drug screening strategy for rapid discovery of inhibitors against the Nsp13 helicase of SARS-CoV-2, Animals and Zoonoses, doi:10.1016/j.azn.2024.06.001.sciencedirect.com, doi.org.

33. Kamble et al., Nanoparticulate curcumin spray imparts prophylactic and therapeutic properties against SARS-CoV-2, Emergent Materials, doi:10.1007/s42247-024-00754-6.springer.com, doi.org.

34. Nicoliche et al., Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2, Scientific Reports, doi:10.1038/s41598-024-61662-7.nature.com, doi.org.

35. Nittayananta et al., A novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity, Virology Journal, doi:10.1186/s12985-023-02282-x.biomedcentral.com, doi.org.

36. Septisetyani et al., Curcumin and turmeric extract inhibited SARS-CoV-2 pseudovirus cell entry and Spike mediated cell fusion, bioRxiv, doi:10.1101/2023.09.28.560070.biorxiv.org, doi.org.

37. Mohd Abd Razak et al., In Vitro Anti-SARS-CoV-2 Activities of Curcumin and Selected Phenolic Compounds, Natural Product Communications, doi:10.1177/1934578X231188861.sagepub.com, doi.org.

38. Fam et al., Channel activity of SARS-CoV-2 viroporin ORF3a inhibited by adamantanes and phenolic plant metabolites, Scientific Reports, doi:10.1038/s41598-023-31764-9.nature.com, doi.org.

39. Teshima et al., Antiviral activity of curcumin and its analogs selected by an artificial intelligence-supported activity prediction system in SARS-CoV-2-infected VeroE6 cells, Natural Product Research, doi:10.1080/14786419.2023.2194647.tandfonline.com, doi.org.

40. Leka et al., In vitro antiviral activity against SARS-CoV-2 of common herbal medicinal extracts and their bioactive compounds, Phytotherapy Research, doi:10.1002/ptr.7463.wiley.com, doi.org.

41. Goc et al., Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants, European Journal of Microbiology and Immunology, doi:10.1556/1886.2021.00022.akjournals.com, doi.org.

42. Marín-Palma et al., Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms, Molecules, doi:10.3390/molecules26226900.mdpi.com, doi.org.

43. Bahun et al., Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols, Food Chemistry, doi:10.1016/j.foodchem.2021.131594.sciencedirect.com, doi.org.

44. Bormann et al., Turmeric Root and Its Bioactive Ingredient Curcumin Effectively Neutralize SARS-CoV-2 In Vitro, Viruses, doi:10.3390/v13101914.mdpi.com, doi.org.

45. Guijarro-Real et al., Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CLPro) Activity, Foods, doi:10.3390/foods10071503.mdpi.com, doi.org.

46. Goc (B) et al., Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions, PLOS ONE, doi:10.1371/journal.pone.0253489.plos.org, doi.org.

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 M^pro, also known as 3CL^pro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting M^pro 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. 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.

h. Non-structural protein 10 (nsp10) serves as an RNA chaperone and stabilizes conformations of nsp12 and nsp14 in the replicase-transcriptase complex, which synthesizes new viral RNAs. Nsp10 disruption may destabilize replicase-transcriptase complex activity.

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 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.

k. 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.

l. 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.

m. 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.

n. 293T is a human embryonic kidney cell line that can be engineered for high ACE2 expression and SARS-CoV-2 susceptibility. 293T cells are easily transfected and support high protein expression.

o. HEK293-hACE2 is a human embryonic kidney cell line with high ACE2 expression and SARS-CoV-2 susceptibility. Cells have been transfected with a plasmid to express the human ACE2 (hACE2) protein.

p. 293T/hACE2/TMPRSS2 is a human embryonic kidney cell line engineered for high ACE2 and TMPRSS2 expression, which mimics key aspects of human infection. 293T/hACE2/TMPRSS2 cells are very susceptible to SARS-CoV-2 infection.

q. 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.

r. SH-SY5Y is a human neuroblastoma cell line that exhibits neuronal phenotypes. It is commonly used as an in vitro model for studying neurotoxicity, neurodegenerative diseases, and neuronal differentiation.

Rajamanickam et al., 20 Feb 2025, India, peer-reviewed, 7 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Curcumin All

Exploring the Potential of Siddha Formulation MilagaiKudineer-Derived Phytotherapeutics Against SARS-CoV-2: An In-Silico Investigation for Antiviral Intervention

Lecturer II Baskar Rajamanickam, Ramesh Balasubramanian, Manekshah Yovas Rajammal, Bharathkumar Govindaraju, Selvapriya Sikkal Selvaraaju, Hemadevi Thangarasu, Kanakavalli Kadarkarai

Journal of Pharmacy and Pharmacology Research, doi:10.26502/fjppr.0105

The search for effective therapeutics against COVID-19 remains imperative, and natural compounds have emerged as promising candidates. Our study explores the potential of bioactive phytochemicals from the traditional Siddha formulation MilagaiKudineer as inhibitors against key target proteins of the SARS-CoV-2 virus. Through in-silico docking analyses, the interactions of phytochemicals from Cuminum cyminum, Curcuma longa, and Capsicum annuum with the receptor-binding domain of the SARS-CoV-2 spike glycoprotein (PDB ID: 6VSB), the SARS-CoV2 RNA-dependent RNA polymerase (PDB ID: 6NUR), and the main protease, 3CL pro (PDB ID: 6LU7) were examined. Notable compounds such as Curcumin, Quercetin, Capsaicin, and Ascorbic acid demonstrated significant binding affinities towards these viral targets, suggesting mechanisms by which these phytochemicals may disrupt viral entry and replication. Our findings also highlight the potential of compounds like Carvacrol, Cuminaldehyde, Linalool, and Dihydrocapsaicin in mediating antiviral effects by interfacing with key amino acid residues of the spike glycoprotein. These interactions are indicative of their capacity to hinder the virus-host cellbinding process. Moreover, the interaction of select phytochemicals with the SARS-CoV2 RNA-dependent RNA polymerase and the 3CLpro enzyme suggests a possible inhibitory effect on viral replication. Given the promising interactions observed, these phytochemicals warrant further investigation through in vitro and in vivo studies to validate their antiviral efficacy against COVID-19. This research underscores the importance of exploring traditional medicinal formulations for potential therapeutic agents in the fight against emerging infectious diseases.

Compounds Conclusion MilagaiKudineer exhibits promising antiviral properties attributed to its constituents. Capsicumannuum Linn (Green chilly) contains capsaicin, which possesses antiviral effects. Cuminum cyminum Linn (Cumin) and Curcuma longa Linn (Turmeric) are known for theirimmunomodulatory and anti-inflammatory properties, which can help combat viral infections. Computational analysis revealed the potential of bioactive compounds from MilagaiKudineer to bind effectively to the receptor-binding domain of the SARS-CoV-2 spike glycoprotein, the SARS-CoV-2 RNA-dependent RNA polymerase and the SARS-CoV-2 Main protease. Compounds such as Carvacrol, Cuminaldehyde, Linalool, Curcumin, Quercetin, Cineol, Dihydrocapsaicin, Capsaicin, and Ascorbic acid hold promise as inhibitors of viral entry and replication, highlighting their potential as therapeutic agents against COVID-19. Furtherexperimental studies are warranted to validate these findings and explore their clinical applications.

References

Aartjan, The RNA polymerase activity of SARScoronavirus nsp12 is primer-dependent, Nucleic Acids Research

Arumugam, Swamy, Sinniah, Plectranthusamboinicus (lour, Spreng: Botanical, phytochemical, pharmacological, and nutritional significance, Molecules, doi:10.3390/molecules21040369

Asan, Palpandian, Nature Mimics, Earth India Siddha Private Limited

Banegas-Luna, Ceron-Carrasco, Perez-Sanchez, A review of ligand-based virtual screening web tools and screening algorithms in large molecular databases in the age of big data, Future Med Chem

Bauer, Mackey, Borgio, Alsuwat, Otaibi et al., Electrostatic complementarity as a fast and effective tool to optimizebindingand selectivityof protein-ligand complexes, Arch Med Sci, doi:10.5114/aoms.2020.94567

Bikadi, Hazai, Application of the PM6 semiempirical method to modeling proteins enhances docking accuracy of AutoDock, J. Cheminf

Cheeseright, Mackey, Rose, Vinter, Molecular field extrema as descriptors of biological activity: definition and validation, J Chem Inf Model

Daina, Michielin, Zoete, SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci Rep

Denyer, Loakes, Young, Isolation ofantirhinoviralsesquiterpenes fromginger(Zingiberofficinale), J Nat Prod

Ei-Sharkawy, Ahmad, Antiviral and Cytotoxic Activities of Som. e Plants Used in Malaysian Indigenous Medicine Pertanika, J Trop Agric Sci

Esmail, The pharmacological activities of Cuminum cyminum -A review, IOSR Journal of Pharmacy

Eweas, Maghrabi, Namarneh, Advances in molecular modeling and docking as a tool for modern drug discovery, Sch Res Lib Der Pharma Chem

Flare, Cresset®, None

Goodsell, Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function, Journal of Computational Chemistry

Goodsell, Zardecki, Di Costanzo, Duarte, Hudson et al., RCSB Protein Data Bank: Enabling biomedical research and drug discovery, Protein Science, doi:10.1002/pro.3730

Guo, Zheng, Hu, Yang, Wang, A comparison of various optimization algorithms of protein-ligand docking programs by fitness accuracy, J Mol Model

Halgren, Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94, Journal of Computational Chemistry

Hamed, Kalita, Bartolo, Jayanty, Capsaicinoids, Polyphenols and Antioxidant Activities of Capsicum annuum: Comparative Study of the Effect of Ripening Stage and Cooking Methods, Antioxidants, doi:10.3390/antiox8090364

Hewlings, Kalman, Curcumin: A Review of Its Effects on Human Health, Foods

Jain, Kumar, Narayanan, Ramaswamy, Sathiyarajeswaran, Exploring the Potential of Siddha Formulation MilagaiKudineer-Derived Phytotherapeutics Against SARS-CoV-2: An In-Silico Investigation for Antiviral Intervention, Journal of Pharmacy and Pharmacology Research, doi:10.1016/j.jaim.2018.05

Jain, Narayanan, Chaturvedi, Pai, Sunil, In vivo evaluation of withaniasomnifera-based Indian traditional formulation (Amukkarachoornam), against chikungunya virus-induced morbidity and arthralgia, J Evid Based Integr Med

Jain, Pai, Sunil, Standardization of in vitro assays to evaluate the activity of polyherbal siddha formulations against Chikungunya virus infection, Virus Dis

Jiang, Liu, Zhang, Luo, Chen, Anti-HBV active constituents from Piper longum, Bioorg Med Chem Lett

Kalikar, Thawani, Varadpande, Singh, Khiyani, Immunomodulatory effect of Tinospora cordifolia extract in human immunodeficiency virus positive patients, Indian J Pharmacol

Koch, Reichling, Schneele, Schnitzler, Inhibitory effect of essential oils against Herpes Simplex virus type 2, Phytomedicine

Kumar, Kumari, Meenakumari, Exploring the Potential of Siddha Formulation MilagaiKudineer-Derived Phytotherapeutics Against COVID-19 Spike Glycoprotein with Receptor-Binding Domain: An In-Silico Investigation for Antiviral Intervention, Frontiers in Pharmacology, doi:10.3389/fphar.2021.757823

Murugesamudaliyar, Directorate of Indian Medicine & Homeopathy

Pereira, Aires-De-Sousa, Computational methodologies in the exploration of the marine natural product leads, Mar Drugs

Rajamanickam, Balasubramanian, Yovas Rajammal, Govindaraju, Sikkal Selvaraaju et al., Exploring the Potential of Siddha Formulation MilagaiKudineer-Derived Phytotherapeutics Against SARS-CoV-2: An In-Silico Investigation for Antiviral Intervention, Journal of Pharmacy and Pharmacology Research

Ramalingam, Annamalai, Sekar, In-silico Identification of Potential Phytochemicals from Siddha Formulation "KabasuraKudineer" against SARS-CoV-2 Spike Protein. Evidence-based Complementary and Alternative Medicine

Ramaswamy, Sathiyarajeswaran, Devi, Srinivasan, Devi, Simple and low-cost process for the preparation of synergistic bio active compound JACOM for the management of H1N1 influenza virus infection

Saravanan, Devasia, Gopalasatheeskumar, Devan, Kokila et al., Antiinflammatory, antipyretic and antibacterial study of Kabasurakudineerchoornam, Int J Curr Adv Res

Selvaraj, Jayaprakash, Arunachalam, Molecular docking analysis of Siddha drug ThirikaduguChooranam on SARS-CoV-2 spike protein, Journal of Traditional and Complementary Medicine

Shahid, Dar, Ismaeel, Al-Mahmeed, Sindi et al., Plant natural products as a potential source of antimicrobial agents: an overview and a glimpse on recent developments

Shaikh, Jain, Sandhu, Latha, Jayaram, From drug target to leads-sketching a physico-chemical pathway for lead molecule design in silico, Curr Pharmaceut Des

Shanmugavelu, Directorate of Indian Medicine & Homeopathy

Shanmugvelu, Noi, Noi, Nadal, None, Chennai: Department of Indian Medicine and Homoeopathy

Singh, Awasthi, Tiwari, Pandey, Dwivedi, Computational approaches for therapeutic application of natural products in Alzheimer's disease, Neuromethods

Sivaraman, Pradeep, AI Vital Finding New Targets for Existing Drugs. Artificial intelligence is harnessed to accelerate drug repurposing in the search for COVID-19 solutions, COVID-19 Engineering Solutions Special Issue

Sivaraman, Pradeep, Revealing Anti-viral Potential of Bio-active Therapeutics Targeting SARS-CoV2-polymerase (RdRp) in Combating COVID-19: Molecular Investigation on Indian Traditional Medicines, Preprints, doi:10.20944/preprints202003.0450.v1

Sivaraman, Pradeep, Scope of phytotherapeutics in targeting ACE2 mediated Host-Viral Interface of SARS-CoV2 that causes COVID-19, ChemRxi, doi:.org/10.26434/chemrxiv.12089730.v1

Sivaraman, Pradeep, Sundar Manoharan, Ramachandra, Bhat et al., Revealing potential binding affinity of FDA approved therapeutics targeting Main protease (3CLpro) in impairing novel coronavirus (SARS-CoV-2) replication that causes COVID-19, Coronaviruses, doi:10.2174/2666796701999200701122817

Solis, Wets, Baskar Rajamanickam, Balasubramanian, Yovas Rajammal et al., Exploring the Potential of Siddha Formulation MilagaiKudineer-Derived Phytotherapeutics Against SARS-CoV-2: An In-Silico Investigation for Antiviral Intervention, Journal of Pharmacy and Pharmacology Research

Sood, Raut, Tyagi, Pareek, Barman et al., Cissampelos pareira Linn: natural source of potent antiviral activity against all four dengue virus serotypes, PLoS Neglected Trop Dis

Srinivasan, Perumal, Nadimuthu, Siddha treatment for COVID-19: A review of recent advances and future prospects, Journal of Traditional and Complementary Medicine

Venkatasubramanian, Priya, Gnanamani, Identification of Potential Anti-SARS-CoV-2 Molecules from Siddha Formulations -An in Silico Approach, European Journal of Molecular & Clinical Medicine

Wadhwa, Mahajan, Barik, Malik, Nargotra, Combining ligand-and structure-based in silico methods for the identification of natural product-based inhibitors of Akt1, Mol Divers

Wang, Liu, Italiani, Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response, Acta Pharmacol Sin

Worachartcheewan, Prachayasittikul, Shoombuatong, Songtawee, Simeon et al., Computer aided drug design of bioactive natural products, Curr Top Med Chem

Wrapp, Wang, Corbett, Goldsmith, Hsieh et al., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation, Science

Zhang, Kitts, Turmeric and its bioactive constituents trigger cell signaling mechanisms that protect against diabetes and cardiovascular diseases, Molecular and cellular biochemistry, doi:10.1007/s11010-021-04201-6

DOI record: { "DOI": "10.26502/fjppr.0105", "ISSN": [ "2578-1553" ], "URL": "http://dx.doi.org/10.26502/fjppr.0105", "abstract": "The search for effective therapeutics against COVID-19 remains imperative, and natural compounds have emerged as promising candidates. Our study explores the potential of bioactive phytochemicals from the traditional Siddha formulation MilagaiKudineer as inhibitors against key target proteins of the SARS-CoV-2 virus. Through in-silico docking analyses, the interactions of phytochemicals from Cuminum cyminum, Curcuma longa, and Capsicum annuum with the receptor-binding domain of the SARS-CoV-2 spike glycoprotein (PDB ID: 6VSB), the SARS-CoV2 RNA-dependent RNA polymerase (PDB ID: 6NUR), and the main protease, 3CL pro (PDB ID: 6LU7) were examined. Notable compounds such as Curcumin, Quercetin, Capsaicin, and Ascorbic acid demonstrated significant binding affinities towards these viral targets, suggesting mechanisms by which these phytochemicals may disrupt viral entry and replication. Our findings also highlight the potential of compounds like Carvacrol, Cuminaldehyde, Linalool, and Dihydrocapsaicin in mediating antiviral effects by interfacing with key amino acid residues of the spike glycoprotein. These interactions are indicative of their capacity to hinder the virus-host cellbinding process. Moreover, the interaction of select phytochemicals with the SARS-CoV2 RNA-dependent RNA polymerase and the 3CLpro enzyme suggests a possible inhibitory effect on viral replication. Given the promising interactions observed, these phytochemicals warrant further investigation through in vitro and in vivo studies to validate their antiviral efficacy against COVID-19. This research underscores the importance of exploring traditional medicinal formulations for potential therapeutic agents in the fight against emerging infectious diseases.", "author": [ { "affiliation": [], "family": "Rajamanickam", "given": "Baskar", "sequence": "first" }, { "affiliation": [], "family": "Balasubramanian", "given": "Ramesh", "sequence": "additional" }, { "affiliation": [], "family": "Yovas Rajammal", "given": "Manekshah", "sequence": "additional" }, { "affiliation": [], "family": "Govindaraju", "given": "Bharathkumar", "sequence": "additional" }, { "affiliation": [], "family": "Sikkal Selvaraaju", "given": "Selvapriya", "sequence": "additional" }, { "affiliation": [], "family": "Thangarasu", "given": "Hemadevi", "sequence": "additional" }, { "affiliation": [], "family": "Kadarkarai", "given": "Kanakavalli", "sequence": "additional" } ], "container-title": "Journal of Pharmacy and Pharmacology Research", "container-title-short": "J Pharm Pharmacol Res", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 4, 11 ] ], "date-time": "2025-04-11T08:04:19Z", "timestamp": 1744358659000 }, "deposited": { "date-parts": [ [ 2025, 4, 11 ] ], "date-time": "2025-04-11T08:04:20Z", "timestamp": 1744358660000 }, "indexed": { "date-parts": [ [ 2025, 4, 12 ] ], "date-time": "2025-04-12T04:05:40Z", "timestamp": 1744430740935, "version": "3.40.4" }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2025, 2, 20 ] ] }, "member": "11040", "original-title": [], "page": "17-27", "prefix": "10.26502", "published": { "date-parts": [ [ 2025, 2, 20 ] ] }, "published-online": { "date-parts": [ [ 2025, 2, 20 ] ] }, "published-print": { "date-parts": [ [ 2025, 2, 20 ] ] }, "publisher": "Fortune Journals", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "https://www.fortunejournals.com/articles/exploring-the-potential-of-siddha-formulation-milagaikudineerderived-phytotherapeutics-against-sarscov2-an-insilico-investigation-.html" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Exploring the Potential of Siddha Formulation MilagaiKudineer-Derived Phytotherapeutics Against SARS-CoV-2: An In-Silico Investigation for Antiviral Intervention", "type": "journal-article" }

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