All Studies Meta Analysis Recent:

Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2

Rampogu et al., International Journal of Molecular Sciences, doi:10.3390/ijms23031771

Feb 2022

Post
Facebook

Source PDF All Studies Meta AnalysisMeta

Curcumin for COVID-19

14th treatment shown to reduce risk in February 2021

^*, now known with p = 0.000000046 from 26 studies.

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

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,100+ studies for 60+ treatments. c19early.org

In Silico molecular dynamics simulation study finding a curcumin analogue (curA) as a promising dual inhibitor for SARS-CoV-2.

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

17 In Vitro studies Bahun, Bormann, Boseila, Eleraky, Goc, Goc (B), Guijarro-Real, Kandeil, Leka, Marín-Palma, Mohd Abd Razak, Nittayananta, Septisetyani, Singh, Teshima, Wu, Zhang

1 In Vivo animal study Boseila

In Silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spike Note A, Nag, Moschovou, Kandeil, Singh (B), Boseila (and specifically the receptor binding domain Note B, Kant, Srivastava, Eleraky), M^pro Note C, Moschovou, Kandeil, Srivastava, Naderi Beni, Rajagopal, Rampogu, Sekiou, Singh, Winih Kinasih, Thapa, Bahun, Eleraky, Boseila, RNA-dependent RNA polymerase Note D, Singh (C), Eleraky, ACE2 Note E, Singh (B), Thapa, Alkafaas, nucleocapsid Note F, Hidayah, Suravajhala, and nsp10 Note G, Suravajhala proteins. In Vitro studies demonstrate inhibition of the spike Note A, Mohd Abd Razak (and specifically the receptor binding domain Note B, Goc (B)), M^pro Note C, Bahun, Guijarro-Real, Mohd Abd Razak, Wu, ACE2 Note E, Goc (B), and TMPRSS2 Note H, Goc (B) proteins. In Vitro studies demonstrate efficacy in Calu-3 Note I, Bormann, A549 Note J, Mohd Abd Razak, 293T Note K, Zhang, HEK293-hACE2 Note L, Nittayananta, Wu, 293T/hACE2/TMPRSS2 Note M, Septisetyani, and Vero E6 Note N, Bormann, Eleraky, Kandeil, Leka, Mohd Abd Razak, Nittayananta, Singh, Teshima, Marín-Palma 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 variants Kant, decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells Marín-Palma, and alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress Zhang.

Important missing comments or errors? Let us know.

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

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

28. 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.

29. 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.

30. 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.

31. 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.

32. Zhang et al., Computational Discovery of Mitochondrial Dysfunction Biomarkers in Severe SARS-CoV-2 Infection: Unveiling Their Functions and Facilitating Drug Screening, Elsevier BV, doi:10.2139/ssrn.4677176.ssrn.com, 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 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.

f. 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.

g. 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.

h. 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.

i. 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.

j. 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.

k. 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.

l. 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.

m. 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.

n. 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.

Rampogu et al., 4 Feb 2022, peer-reviewed, 5 authors.

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

This Paper Curcumin All

Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2

Shailima Rampogu, Gihwan Lee, Jun Sung Park, Keun Woo Lee, Myeong Ok Kim

International Journal of Molecular Sciences, doi:10.3390/ijms23031771

Recently, the world has been witnessing a global pandemic with no effective therapeutics yet, while cancer continues to be a major disease claiming many lives. The natural compound curcumin is bestowed with multiple medicinal applications in addition to demonstrating antiviral and anticancer activities. In order to elucidate the impact of curcumin on COVID-19 and cancer, the current investigation has adapted several computational techniques to unfold its possible inhibitory activity. Accordingly, curcumin and similar compounds and analogues were retrieved and assessed for their binding affinities at the binding pocket of SARS-CoV-2 main protease and DDX3. The best binding pose was escalated to molecular dynamics simulation (MDS) studies to assess the time dependent stability. Our findings have rendered one compound that has demonstrated good molecular dock score complemented by key residue interactions and have shown stable MDS results inferred by root mean square deviation (RMSD), radius of gyration (Rg), binding mode, hydrogen bond interactions, and interaction energy. Essential dynamics results have shown that the systemadapts minimum energy conformation to attain a stable state. The discovered compound (curA) could act as plausible inhibitor against SARS-CoV-2 and DDX3. Furthermore, curA could serve as a chemical scaffold for designing and developing new compounds.

Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/ijms23031771/s1. Conflicts of Interest: The authors declare no conflict of interest.

References

Aier, Varadwaj, Raj, Structural insights into conformational stability of both wild-type and mutant EZH2 receptor, Sci. Rep, doi:10.1038/srep34984

Alexpandi, De Mesquita, Pandian, Ravi, Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: An in silico Analysis, Front. Microbiol, doi:10.3389/fmicb.2020.01796

Atanasov, Zotchev, Dirsch, Orhan, Banach et al., Natural products in drug discovery: Advances and opportunities, Nat. Rev. Drug Discov, doi:10.1038/s41573-020-00114-z

Bhardwaj, Singh, Das, Purohit, Evaluation of acridinedione analogs as potential SARS-CoV-2 main protease inhibitors and their comparison with repurposed anti-viral drugs, Comput. Biol. Med, doi:10.1016/j.compbiomed.2020.104117

Bimonte, Barbieri, Palma, Rea, Luciano et al., Dissecting the Role of Curcumin in Tumour Growth and Angiogenesis in Mouse Model of Human Breast Cancer, Biomed Res. Int, doi:10.1155/2015/878134

Bol, Xie, Raman, DDX3, a potential target for cancer treatment, Mol. Cancer, doi:10.1186/s12943-015-0461-7

Botlagunta, Kollapalli, Kakarla, Gajarla, Gade et al., In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3, Bioinformation, doi:10.6026/97320630012347

Ciccosanti, Di Rienzo, Romagnoli, Colavita, Refolo et al., Proteomic analysis identifies the RNA helicase DDX3X as a host target against SARS-CoV-2 infection, Antivir. Res, doi:10.1016/j.antiviral.2021.105064

Fakhar, Khan, Alomar, Alkhuriji, Ahmad, ABBV-744 as a potential inhibitor of SARS-CoV-2 main protease enzyme against COVID-19, Sci. Rep, doi:10.1038/s41598-020-79918-3

Frecer, Miertus, Antiviral agents against COVID-19: Structure-based design of specific peptidomimetic inhibitors of SARS-CoV-2 main protease, RSC Adv, doi:10.1039/D0RA08304F

Gahlawat, Kumar, Kumar, Sandhu, Singh et al., Structure-Based Virtual Screening to Discover Potential Lead Molecules for the SARS-CoV-2 Main Protease, J. Chem. Inf. Model, doi:10.1021/acs.jcim.0c00546

Ghahremanpour, Tirado-Rives, Deshmukh, Ippolito, Zhang et al., Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2, ACS Med. Chem. Lett, doi:10.1021/acsmedchemlett.0c00521

Giordano, Tommonaro, Curcumin and Cancer, Nutrients, doi:10.3390/nu11102376

Guo, Xie, Lei, Liu, Zhang et al., Discovery of novel inhibitors against main protease (Mpro) of SARS-CoV-2 via virtual screening and biochemical evaluation, Bioorg. Chem, doi:10.1016/j.bioorg.2021.104767

He, Zhang, Yang, Wang, Zhao et al., A double-edged function of DDX3, as an oncogene or tumor suppressor, in cancer progression (Review), Oncol. Rep, doi:10.3892/or.2018.6203

Hospital, Goñi, Orozco, Gelpí, Molecular dynamics simulations: Advances and applications, Adv. Appl. Bioinform. Chem, doi:10.2147/AABC.S70333

Hu, Xu, Meng, Huang, Sun, Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells, Exp. Ther. Med, doi:10.3892/etm.2018.6345

Humphrey, Dalke, Schulten, Vmd, Visual molecular dynamics, J. Mol. Graph, doi:10.1016/0263-7855(96)00018-5

Högbom, Collins, Van Den Berg, Jenvert, Karlberg et al., Crystal Structure of Conserved Domains 1 and 2 of the Human DEAD-box Helicase DDX3X in Complex with the Mononucleotide AMP, J. Mol. Biol, doi:10.1016/j.jmb.2007.06.050

Jena, Kanungo, Nayak, Chainy, Dandapat, Catechin and curcumin interact with S protein of SARS-CoV2 and ACE2 of human cell membrane: Insights from computational studies, Sci. Rep, doi:10.1038/s41598-021-81462-7

Jin, Du, Xu, Deng, Liu et al., Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors, Nature, doi:10.1038/s41586-020-2223-y

Kim, Chen, Cheng, Gindulyte, He et al., PubChem in 2021: New data content and improved web interfaces, Nucleic Acids Res, doi:10.1093/nar/gkaa971

Kumar, Bhardwaj, Kumar, Gehi, Kapuganti et al., Reprofiling of approved drugs against SARS-CoV-2 main protease: An in-silico study, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1845976

Kumar, Nyodu, Maurya, Saxena, Morphology, Genome Organization, Replication, and Pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Epidemiol. Pathog. Diagn. Ther

Kumar, Sodhi, Singh, Addressing the potential role of curcumin in the prevention of COVID-19 by targeting the Nsp9 replicase protein through molecular docking, Arch. Microbiol, doi:10.1007/s00203-020-02163-9

Kumar, Swetha, Anbarasu, Ramaiah, Computational analysis reveals the association of threonine 118 methionine mutation in PMP22 resulting in CMT-1A, Adv. Bioinform, doi:10.1155/2014/502618

Li, Li, Huang, Wu, Liu et al., Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs, BioRxiv, doi:10.1073/pnas.2010470117

Lin, Hsu, Lin, Antiviral natural products and herbal medicines, J. Tradit. Complement. Med

Liu, Ying, The Inhibitory Effect of Curcumin on Virus-Induced Cytokine Storm and Its Potential Use in the Associated Severe Pneumonia, Front. Cell Dev. Biol, doi:10.3389/fcell.2020.00479

Manoharan, Haridas, Vasanthakumar, Muthu, Thavoorullah et al., Curcumin: A Wonder Drug as a Preventive Measure for COVID19 Management, Indian J. Clin. Biochem, doi:10.1007/s12291-020-00902-9

Mansouri, Rasoulpoor, Daneshkhah, Abolfathi, Salari et al., Clinical effects of curcumin in enhancing cancer therapy: A systematic review, BMC Cancer, doi:10.1186/s12885-020-07256-8

Marín-Palma, Tabares-Guevara, Zapata-Cardona, Flórez-Álvarez, Yepes et al., Curcumin Inhibits in Vitro SARS-CoV-2 Infection in Vero E6 Cells through Multiple Antiviral Mechanisms, Molecules, doi:10.3390/molecules26226900

Mathew, Hsu, Antiviral potential of curcumin, J. Funct. Foods, doi:10.1016/j.jff.2017.12.017

Mishra, Pandey, Sharma, Malik, Mongre et al., Identifying the natural polyphenol catechin as a multi-targeted agent against SARS-CoV-2 for the plausible therapy of COVID-19: An integrated computational approach, Brief. Bioinform, doi:10.1093/bib/bbaa378

Mo, Liang, Su, Li, Chen et al., DDX3X: Structure, physiologic functions and cancer, Mol. Cancer, doi:10.1186/s12943-021-01325-7

Mohammed, Rashid-Doubell, Taha, Cassidy, Fredericks, Effects of curcumin complexes on MDA-MB-231 breast cancer cell proliferation, Int. J. Oncol, doi:10.3892/ijo.2020.5065

Naqvi, Fatima, Mohammad, Fatima, Singh et al., Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach, Biochim. Biophys. Acta Mol. Basis Dis, doi:10.1016/j.bbadis.2020.165878

Nguyen, Gao, Chen, Wang, Wei, Unveiling the molecular mechanism of SARS-CoV-2 main protease inhibition from 137 crystal structures using algebraic topology and deep learning, Chem. Sci, doi:10.1039/D0SC04641H

Noureddin, El-Shishtawy, Al-Footy, Curcumin analogues and their hybrid molecules as multifunctional drugs, Eur. J. Med. Chem, doi:10.1016/j.ejmech.2019.111631

Patel, Rajendran, Shah, Patel, Pakala et al., Virtual screening of curcumin and its analogs against the spike surface glycoprotein of SARS-CoV-2 and SARS-CoV, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1868338

Quaranta, Lottini, Chesi, Contrafatto, Russotto et al., DDX3 inhibitors show antiviral activity against positive-sense single-stranded RNA viruses but not against negative-sense single-stranded RNA viruses: The coxsackie B model, Antivir. Res, doi:10.1016/j.antiviral.2020.104750

Rampogu, Kim, Son, Baek, Park et al., A computational approach with biological evaluation: Combinatorial treatment of curcumin and exemestane synergistically regulates ddx3 expression in cancer cell lines, Biomolecules, doi:10.3390/biom10060857

Rampogu, Lee, Old Drugs for New Purpose-Fast Pace Therapeutic Identification for SARS-CoV-2 Infections by Pharmacophore Guided Drug Repositioning Approach, Bull. Korean Chem. Soc, doi:10.1002/bkcs.12171

Rampogu, Lemuel, Lee, Virtual screening, molecular docking, molecular dynamics simulations and free energy calculations to discover potential DDX3 inhibitors, Adv. Cancer Biol.-Metastasis, doi:10.1016/j.adcanc.2021.100022

Rampogu, Parameswaran, Lemuel, Lee, Exploring the Therapeutic Ability of Fenugreek against Type 2 Diabetes and Breast Cancer Employing Molecular Docking and Molecular Dynamics Simulations, Evid.-Based Complement. Altern. Med, doi:10.1155/2018/1943203

Sacco, Ma, Lagarias, Gao, Townsend et al., Structure and inhibition of the SARS-CoV-2 main protease reveal strategy for developing dual inhibitors against Mpro and Cathepsin L, Sci. Adv, doi:10.1126/sciadv.abe0751

Samal, Routray, Veeramachaneni, Dash, Botlagunta, Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer, Sci. Rep, doi:10.1038/srep09982

Shanmugarajan, Prabitha, Kumar, Suresh, Curcumin to inhibit binding of spike glycoprotein to ACE2 receptors: Computational modelling, simulations, and ADMET studies to explore curcuminoids against novel SARS-CoV-2 targets, RSC Adv, doi:10.1039/D0RA03167D

Soni, Mehta, Ratre, Tiwari, Amit et al., Curcumin, a traditional spice component, can hold the promise against COVID-19?, Eur. J. Pharmacol, doi:10.1016/j.ejphar.2020.173551

Thimmulappa, Mudnakudu-Nagaraju, Shivamallu, Subramaniam, Radhakrishnan et al., Antiviral and immunomodulatory activity of curcumin: A case for prophylactic therapy for COVID-19, Heliyon, doi:10.1016/j.heliyon.2021.e06350

Thulasi Raman, Liu, Pyo, Cui, Xu et al., DDX3 Interacts with Influenza A Virus NS1 and NP Proteins and Exerts Antiviral Function through Regulation of Stress Granule Formation, J. Virol, doi:10.1128/JVI.03010-15

Valiente-Echeverría, Hermoso, Soto-Rifo, RNA helicase DDX3: At the crossroad of viral replication and antiviral immunity, Rev. Med. Virol, doi:10.1002/rmv.1845

Van Der Spoel, Lindahl, Hess, Groenhof, Mark et al., GROMACS: Fast, flexible, and free, J. Comput. Chem, doi:10.1002/jcc.20291

Van Voss, Vesuna, Trumpi, Brilliant, Berlinicke et al., Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer, Oncotarget, doi:10.18632/oncotarget.4873

Vyas, Dandawate, Padhye, Ahmad, Sarkar, Perspectives on new synthetic curcumin analogs and their potential anticancer properties, Curr. Pharm. Des

Wu, Robertson, Brooks, Vieth, Detailed analysis of grid-based molecular docking: A case study of CDOCKER-A CHARMm-based MD docking algorithm, J. Comput. Chem, doi:10.1002/jcc.10306

Wu, Wu, Liu, Yang, The SARS-CoV-2 outbreak: What we know, Int. J. Infect. Dis, doi:10.1016/j.ijid.2020.03.004

Yang, Xiao, Ye, He, Sun et al., SARS-CoV-2: Characteristics and current advances in research, Virol. J, doi:10.1186/s12985-020-01369-z

Zoete, Cuendet, Grosdidier, Michielin, SwissParam: A fast force field generation tool for smallorganic molecules, J. Comput. Chem, doi:10.1002/jcc.21816

Download Image

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ 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. FLCCC and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0