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Bioinformatics study of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin compounds in Curcuma longa as an antiviral agent via nucleocapsid on SARS-CoV-2 inhibition

Hidayah et al., International Conference on Organic and Applied Chemistry, doi:10.1063/5.0197724
Feb 2024  
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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.
5,100+ studies for 112 treatments. c19early.org
In Silico study showing binding of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin to the SARS-CoV-2 nucleocapsid protein. Authors find curcumin has the strongest predicted binding affinity. All compounds showed suitable pharmacokinetic properties. Binding is predicted to inhibit viral genome replication and transcription by disrupting ribonucleoprotein complex formation.
51 preclinical studies support the efficacy of curcumin for COVID-19:
26 In Silico studies1-26
24 In Vitro studies1,3,7,9,13,19,23,27-43
1 In Vivo animal study7
In Silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spikeA,2,7,12,14,20,23,44 (and specifically the receptor binding domainB,10,13,16), MproC,2,7,9,11-13,15,16,18,21,23,24,26,40,44, RNA-dependent RNA polymeraseD,2,13,22,44, PLproE,2, ACE2F,14,15,17, nucleocapsidG,8,25, nsp10H,25, and helicaseI,29 proteins. In Vitro studies demonstrate inhibition of the spikeA,34 (and specifically the receptor binding domainB,43), MproC,19,34,40,42, ACE2F,43, and TMPRSS2J,43 proteins, and inhibition of spike-ACE2 interactionK,27. In Vitro studies demonstrate efficacy in Calu-3L,41, A549M,34, 293TN,3, HEK293-hACE2O,19,32, 293T/hACE2/TMPRSS2P,33, Vero E6Q,9,13,23,32,34,36,37,39,41, and SH-SY5YR,31 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 variants10, decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells39, alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress3, 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 fibroblasts45, and inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity35.
Important missing comments or errors? Let us know.
a. The trimeric spike (S) protein is a glycoprotein that mediates viral entry by binding to the host ACE2 receptor, is critical for SARS-CoV-2's ability to infect host cells, and is a target of neutralizing antibodies. Inhibition of the spike protein prevents viral attachment, halting infection at the earliest stage.
b. The receptor binding domain is a specific region of the spike protein that binds ACE2 and is a major target of neutralizing antibodies. Focusing on the precise binding site allows highly specific disruption of viral attachment with reduced potential for off-target effects.
c. The main protease or Mpro, also known as 3CLpro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting Mpro disrupts the SARS-CoV-2 lifecycle within the host cell, preventing the creation of new copies.
d. RNA-dependent RNA polymerase (RdRp), also called nsp12, is the core enzyme of the viral replicase-transcriptase complex that copies the positive-sense viral RNA genome into negative-sense templates for progeny RNA synthesis. Inhibiting RdRp blocks viral genome replication and transcription.
e. The papain-like protease (PLpro) has multiple functions including cleaving viral polyproteins and suppressing the host immune response by deubiquitination and deISGylation of host proteins. Inhibiting PLpro may block viral replication and help restore normal immune responses.
f. The angiotensin converting enzyme 2 (ACE2) protein is a host cell transmembrane protein that serves as the cellular receptor for the SARS-CoV-2 spike protein. ACE2 is expressed on many cell types, including epithelial cells in the lungs, and allows the virus to enter and infect host cells. Inhibition may affect ACE2's physiological function in blood pressure control.
g. 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. 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.
k. 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.
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.
Hidayah et al., 6 Feb 2024, peer-reviewed, 3 authors. Contact: rizkanurulh@student.ub.ac.id, dewi.santosa@ub.ac.id, roihatulmutiah@gmail.com.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Bioinformatics study of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin compounds in Curcuma longa as an antiviral agent via nucleocapsid on SARS-CoV-2 inhibition
Rizka Nurul Hidayah, Dewi Santosaningsih, Roihatul Muti’ah
doi:10.1063/5.0197724
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a higher reproduction rate (R0) than SARS-CoV-1 is assessed to be 2.5 contrasted with 2.0-3.0 for SARS-CoV, indicating a much faster spread. During the replication process, the viral ribonucleic acid (RNA) genome is bound to the nucleocapsid and packaged into a ribonucleoprotein complex (RNP) which is essential for maintaining RNA conformation for genome replication and copy. Antiviral agents are given to prevent the replication area from expanding. In silico simulation was used to predict an interaction between Curcuma longa compound as an Antiviral agent by inhibiting viral RNA transcription and replication through inhibiting the activity of the nucleocapsid during the screening of a new compound as a drug candidate. The Nucleocapsid structures were used to create the protein target from Protein Data Bank. PubChem online tool was used to determine the structure of Curcumin, Demethoxycurcumin, Bisdemethoxycurcumin, and Cyclocurcumin as ligands. With the help of software like pkCSM, Protox, and SwissADME, these structures are analyzed for pharmacokinetics and physicochemistry interactions. To predict the most probable compliance of how the ligand will tie to the macromolecule evaluated through the action of the compound in light of the Rerank Score using the Molegro Virtual Docker 6.0 software. When curcumin binds to 6VYO, it has the lowest bond energy (-73,8743 Kcal/mol) than the native ligand and comparison drug Chloroquine (-60.438 Kcal/mol and -59.062 Kcal/mol, respectively). These findings tend to inhibit the role of nucleocapsids in the binding of viral RNA genomes and the packaging process into ribonucleoprotein complexes (RNPs), leading to the prevention of viral infection, replication, and packaging processes of the virus.
References
Allen, Mervin, Mahmoud, Bender, None, J Cheminform, doi:10.1186/s13321-019-0356-5
Ashraf, Sultan, Campus, Alam, Darul Ehsan, None, International Journal of Green Pharmacy
Askarizadeh, Barreto, Henney, Majeed, Sahebkar, None, International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2020.119476
Cevik, Kuppalli, Kindrachuk, Peiris, None, The BMJ
Chen, Li, Tian, Li, Luo et al., None, Journal of Computational Biology, doi:10.1089/cmb.2019.0323
Chen, None, Research on Chemical Intermediates, doi:10.1007/s11164-016-2583-y
Cong, None, J Virol, doi:10.1128/JVI.01925-19
Dona, Frimayanti, Ikhtiarudin, Iskandar, Maulana et al., None, Jurnal Sains Farmasi & Klinis, doi:10.25077/jsfk.6.3.243-249.2019
Fu, Chen, Zhang, Yu, Yang, None, Int. J. Mol. Med
Fu, Chen, Zhang, Yu, Yang, None, Int. J. Mol. Med, doi:10.3892/ijmm.2017.2926
Guan, None, New England Journal of Medicine, doi:10.1056/NEJMoa2002032
Hamm, None, Regulatory Toxicology and Pharmacology, doi:10.1016/j.yrtph.2021.105007
Kang, None, Acta Pharm Sin B
Khan, None, Comput Struct Biotechnol J, doi:10.1016/j.csbj.2020.08.006
Kwarteng, Asiedu, Sakyi, Asiedu, None, Biomedicine and Pharmacotherapy
Lang, Chen, Li, Li, None, Life Sciences, doi:10.1016/j.lfs.2020.118754
Marazzi, Francés-Monerris, Mourer, Pasc, Monari, None, Physical Chemistry Chemical Physics, doi:10.1039/C9CP06565B
Mazhir, Ali, Kadhim, Majeed, None, Journal of Physics
Megasari, None, PLoS One, doi:10.1371/journal.pone.0251234
Mitsuwan, None, Int J Parasitol Drugs Drug Resist, doi:10.1016/j.ijpddr.2020.11.001
Oyesakin, George, Fadare R Y, Idris, Fadare, None, Am J Pharmacol Sci
Petersen, None, Lancet Infect Dis, doi:10.1016/S1473-3099(20)30484-9
Rim, None, Toxicol Environ Health Sci, doi:10.1007/s13530-020-00056-4
Rothwell, None, The Journal of Biological Databases and Curation
Ruswanto, Wulandari, Rahayu, Mardaningrum, Hidayati, None, Pharmacosricpt
Santos, Ferreira, Caffarena, None, Methods in Molecular Biology, doi:10.1007/978-1-4939-9752-7_2
Shafhan Arfi, Lestari, Damayanti, None
Suhartati, Anugrah, Raharja, None
Syarif, None, Jurnal Kedokteran Brawijaya, doi:10.21776/ub.jkb.2016.029.01.7
Tung, Nham, Hai, Thu, None
Wang, None, RSC Adv, doi:10.1039/C6RA28442F
Wolfram, Trifan, None, Computational Phytochemistry
Wu, Ta, Lung, Weng, Leong, None, Pharmaceutics
Zeng, Deng, Dang, Yu, None, Sci Rep
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