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Potential of turmeric-derived compounds against RNA-dependent RNA polymerase of SARS-CoV-2: An in-silico approach

Singh et al., Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2021.104965

Oct 2021

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Curcumin for COVID-19

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In Silico study showing strong binding affinity of curcumin and diacetylcurcumin with SARS-CoV-2 RNA-dependent RNA polymerase. Comparison with remdesivir and favipiravir suggested greater potential of these compounds as an RdRp inhibitor.

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.

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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.

Singh et al., 22 Oct 2021, peer-reviewed, 3 authors.

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

This Paper Curcumin All

Potential of turmeric-derived compounds against RNA‐dependent RNA polymerase of SARS‐CoV‐2: An in-silico approach

Rahul Singh, Vijay Kumar Bhardwaj, Rituraj Purohit

Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2021.104965

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Competing interests All authors hereby declare that they have no competing interests related to this work. J o u r n a l P r e -p r o o f

References

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

Bhardwaj, Singh, Sharma, Rajendran, Purohit et al., Bioactive molecules of Tea as potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2, Front. Med, doi:10.3389/FMED.2021.684020.JournalPre-proof

Bhardwaj, Singh, Sharma, Rajendran, Purohit et al., Identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1766572

Chan, Yuan, Kok, To, Chu et al., A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster, Lancet, doi:10.1016/S0140-6736(20)30154-9

Chen, Zhou, Dong, Qu, Gong et al., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, Lancet, doi:10.1016/S0140-6736(20

Darden, York, Pedersen, Particle mesh Ewald: An N•log(N) method for Ewald sums in large systems, J. Chem. Phys, doi:10.1063/1.464397

Ebrahimi, Ansari, Hosseyni Moghaddam, Ebrahimi, Salehi et al., In silico investigation on the inhibitory effect of fungal secondary metabolites on RNA dependent RNA polymerase of SARS-CoV-II: A docking and molecular dynamic simulation study, Comput. Biol. Med, doi:10.1016/J.COMPBIOMED.2021.104613

Gao, Yan, Huang, Liu, Zhao et al., Structure of the RNAdependent RNA polymerase from COVID-19 virus, Science, doi:10.1126/science.abb7498

Gong, Peersen, Structural basis for active site closure by the poliovirus RNAdependent RNA polymerase, Proc. Natl. Acad. Sci. U. S. A, doi:10.1073/pnas.1007626107

Gordon, Tchesnokov, Woolner, Perry, Feng et al., Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency, J. Biol. Chem, doi:10.1074/jbc.RA120.013679

Hess, Bekker, Berendsen, Fraaije, LINCS: A Linear Constraint Solver for molecular simulations, J. Comput. Chem

Hillen, Kokic, Farnung, Dienemann, Tegunov et al., Structure of replicating SARS-CoV-2 polymerase, Nature, doi:10.1038/s41586-020-2368-8

Holshue, Debolt, Lindquist, Lofy, Wiesman et al., First Case of 2019 Novel Coronavirus in the United States, N. Engl. J. Med, doi:10.1056/nejmoa2001191

Hosseini, Chen, Xiao, Wang, Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs, Precis, Clin. Med, doi:10.1093/pcmedi/pbab001

Kirchdoerfer, Ward, Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors, Nat. Commun, doi:10.1038/s41467-019-10280-3.JournalPre-proof

Koulgi, Jani, Mallikarjunachari Uppuladinne, Sonavane, Joshi, Natural plant products as potential inhibitors of RNA dependent RNA polymerase of Severe Acute Respiratory Syndrome Coronavirus-2, PLoS One, doi:10.1371/journal.pone.0251801

Kumar, Bhardwaj, Singh, Purohit, Explicit-solvent molecular dynamics simulations revealed conformational regain and aggregation inhibition of I113T SOD1 by Himalayan bioactive molecules, J. Mol. Liq, doi:10.1016/j.molliq.2021.116798

Kumari, Kumar, Lynn, G-mmpbsa -A GROMACS tool for high-throughput MM-PBSA calculations, J. Chem. Inf. Model, doi:10.1021/ci500020m

Lehmann, Gulyaeva, Zevenhoven-Dobbe, Janssen, Ruben et al., Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses, Nucleic Acids Res, doi:10.1093/nar/gkv838

Mcdonald, RNA synthetic mechanisms employed by diverse families of RNA viruses, Wiley Interdiscip. Rev. RNA, doi:10.1002/wrna.1164

Moghadamtousi, Abdul Kadir, Hassandarvish, Tajik, Abubakar et al., A review on antibacterial, antiviral, and antifungal activity of curcumin, Biomed Res. Int, doi:10.1155/2014/186864

Mounce, Cesaro, Carrau, Vallet, Vignuzzi, Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding, Antiviral Res, doi:10.1016/j.antiviral.2017.03.014

Niranjan, Singh, Dhiman, Tewari, Biochemical Composition of Curcuma longa L. Accessions, Anal. Lett, doi:10.1080/00032719.2012.751541

Parrinello, Rahman, Polymorphic transitions in single crystals: A new molecular dynamics method, J. Appl. Phys, doi:10.1063/1.328693

Priyadarsini, The chemistry of curcumin: From extraction to therapeutic agent, Molecules, doi:10.3390/molecules191220091

Rajagopal, Varakumar, Baliwada, Byran, Activity of phytochemical constituents of Curcuma longa (turmeric) and Andrographis paniculata against coronavirus (COVID-19): an in silico approach, Futur. J. Pharm. Sci, doi:10.1186/s43094-020-00126-x

Rattis, Ramos, Celes, Curcumin as a Potential Treatment for COVID-19, Front. Pharmacol, doi:10.3389/fphar.2021.675287

Shannon, Le, Selisko, Eydoux, Alvarez et al., Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites, Antiviral Res, doi:10.1016/j.antiviral.2020.104793

Sharma, Bhardwaj, Singh, Rajendran, Purohit et al., An in-silico evaluation of different bioactive molecules of Tea for their inhibition potency against non structural protein-15 of SARS-CoV-2, Food Chem, doi:10.1016/j.foodchem.2020.128933

Singh, Bhardwaj, Das, Purohit, A computational approach for rational discovery of inhibitors for non-structural protein 1 of SARS-CoV-2, Comput. Biol. Med, doi:10.1016/j.compbiomed.2021.104555

Singh, Bhardwaj, Sharma, Kumar, Purohit, Identification of potential plant bioactive as SARS-CoV-2 Spike protein and human ACE2 fusion inhibitors, Comput. Biol. Med, doi:10.1016/J.COMPBIOMED.2021

Singh, Bhardwaj, Sharma, Purohit, Kumar, In-silico evaluation of bioactive compounds from tea as potential SARS-CoV-2 nonstructural protein 16 inhibitors, J. Tradit. Complement. Med, doi:10.1016/j.jtcme.2021.05.005

Skariyachan, Gopal, Muddebihalkar, Uttarkar, Niranjan, Structural insights on the interaction potential of natural leads against major protein targets of SARS-CoV-2: Molecular modelling, docking and dynamic simulation studies, Comput. Biol. Med, doi:10.1016/J.COMPBIOMED.2021.104325

Studio, Dassault Systemes BIOVIA

Subissi, Posthuma, Collet, Zevenhoven-Dobbe, Gorbalenya et al., One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities, Proc. Natl. Acad. Sci. U. S. A, doi:10.1073/pnas.1323705111

Umashankar, Deshpande, Hegde, Singh, Chattopadhyay, Phytochemical Moieties From Indian Traditional Medicine for Targeting Dual Hotspots on SARS-CoV-2

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

Vanommeslaeghe, Hatcher, Acharya, Kundu, Zhong et al., CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields, J. Comput. Chem, doi:10.1002/jcc.21367.JournalPre-proof

Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res, doi:10.1038/s41422-020-0282-0

Yin, Mao, Luan, Shen, Shen et al., Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir, Science, doi:10.1126/science.abc1560

Zheng, Frisch, Efficient Geometry Minimization and Transition Structure Optimization Using Interpolated Potential Energy Surfaces and Iteratively Updated Hessians, J. Chem. Theory Comput, doi:10.1021/acs.jctc.7b00719

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