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In silico studies of anti-oxidative and hot temperament-based phytochemicals as natural inhibitors of SARS-CoV-2 Mpro

Naderi Beni et al., PLOS ONE, doi:10.1371/journal.pone.0295014

Nov 2023

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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 potential benefits of the phytochemicals curcumin, savinin, and betulinic acid as an inhibitor of the SARS-CoV-2 main protease (M^pro). Molecular docking analysis revealed these hot temperament, antioxidant compounds bind strongly to both monomeric and dimeric forms of M^pro, with the higest predicted binding affinity for betulinic acid. MD simulations confirmed curcumin forms multiple hydrogen bonds with active site residues. MM-PBSA calculations also showed favorable binding free energy for the curcumin-M^pro complex. Additionally, ADMET analysis revealed curcumin satisfies criteria for drug-likeness. By targeting the viral protease, curcumin may inhibit SARS-CoV-2 replication.

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), M^proC,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), M^proC,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.

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1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

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

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

43. 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.

44. Al balawi (B) 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.

45. Van Tin (B) 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.

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. 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.

Naderi Beni et al., 30 Nov 2023, peer-reviewed, 4 authors. Contact: a.seyedarabi@ut.ac.ir, s.gharaghani@ut.ac.ir.

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

This Paper Curcumin All

In silico studies of anti-oxidative and hot temperament-based phytochemicals as natural inhibitors of SARS-CoV-2 Mpro

Ramin Naderi Beni, Parisa Elyasi-Ebli, Sajjad Gharaghani, Arefeh Seyedarabi

PLOS ONE, doi:10.1371/journal.pone.0295014

Main protease (M pro ) of SARS-CoV-2 is considered one of the key targets due to its role in viral replication. The use of traditional phytochemicals is an important part of complementary/alternative medicine, which also accompany the concept of temperament, where it has been shown that hot medicines cure cold and cold medicines cure hot, with cold and hot pattern being associated with oxidative and anti-oxidative properties in medicine, respectively. Molecular docking in this study has demonstrated that a number of anti-oxidative and hot temperament-based phytochemicals have high binding affinities to SARS-CoV-2 M pro , both in the monomeric and dimeric deposited states of the protein. The highest ranking phytochemicals identified in this study included savinin, betulinic acid and curcumin. Complexes of savinin, betulinic acid, curcumin as well as Nirmatrelvir (the only approved inhibitor, used for comparison) bound to SARS-CoV-2 M pro were further subjected to molecular dynamics simulations. Subsequently, RMSD, RMSF, Rg, number of hydrogen bonds, binding free energies and residue contributions (using MM-PBSA) and buried surface area (BSA), were analysed. The computational results suggested high binding affinities of savinin, betulinic acid and curcumin to both the monomeric and dimeric deposited states of M pro , while highlighting the lower binding energy of betulinic acid in comparison with savinin and curcumin and even Nirmatrelvir, leading to a greater stability of the betulinic acid-SARS-CoV-2 M pro complex. Overall, based on the increasing mutation rate in the spike protein and the fact that the SARS-CoV-2 M pro remains highly conserved, this study provides an insight into the use of phytochemicals against COVID-19 and other coronavirus diseases.

Richards and Lee method with a water probe size of 1.4 Å [63] . Subsequently, the BSA was calculated using the formula BSA = 0.5*(SASA ligand + SASA protein-SASA complex). Supporting information S1

References

Abraham, GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX

Afzali, The Relationship between the Severity of the COVID-19 Disease, Temperament and Psychological Factors, Iranian Journal of Psychiatry

Al-Khafaji, Al-Duhaidahawi, Tok, Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2020.1764392

Alhadrami, Olive-derived triterpenes suppress SARS COV-2 main protease: a promising scaffold for future therapeutics, Molecules, doi:10.3390/molecules26092654

Anand, Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs, Science, doi:10.1126/science.1085658

Baker, Electrostatics of nanosystems: Application to microtubules and the ribosome, Proceedings of the National Academy of Sciences, doi:10.1073/pnas.181342398

Bazzano, Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, The American journal of clinical nutrition, doi:10.1093/ajcn/76.1.93

Berendsen, Molecular dynamics with coupling to an external bath, The Journal of chemical physics

Callaway, The mutation that helps Delta spread like wildfire, Nature, doi:10.1038/d41586-021-02275-2

Cascella, Rajnik, Cuomo, Features, Evaluation, and Treatment of Coronavirus (COVID-19)

Chao, Effects of hot and cold foods on signals of heart rate variability and nail fold microcirculation of healthy young humans: a pilot study, Chinese Journal of Physiology

Dai, Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease, Science, doi:10.1126/science.abb4489

De Magalhães, A dynamic niching genetic algorithm strategy for docking highly flexible ligands, Information Sciences

Ebenezer, Shapi, Promising inhibitors against main protease of SARS CoV-2 from medicinal plants: In silico identification, Acta Pharmaceutica, doi:10.2478/acph-2022-0020

Farsani, Is the Iranian Traditional Medicine warm and cold temperament related to Basal Metabolic Rate and activity of the sympathetic-parasympathetic system? Study protocol, Journal of Diabetes & Metabolic Disorders

Guedes, New machine learning and physics-based scoring functions for drug discovery, Scientific reports

Hall, Jr, A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease, Travel medicine and infectious disease, doi:10.1016/j.tmaid.2020.101646

Haug, Arora, Matsui, A steepest-descent method for optimization of mechanical systems, Journal of Optimization Theory and Applications

Huang, Mackerell, CHARMM36 all-atom additive protein force field: Validation based on comparison to NMR data, Journal of computational chemistry, doi:10.1002/jcc.23354

Humphrey, Dalke, Schulten, VMD-Visual Molecular Dynamics, J. Molec. Graphics, doi:10.1016/0263-7855%2896%2900018-5

Jorgensen, Comparison of simple potential functions for simulating liquid water, The Journal of chemical physics

Kandeel, Al-Nazawi, Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease, Life sciences, doi:10.1016/j.lfs.2020.117627

Kao, Effects of Ding-Chuan-Tang on bronchoconstriction and airway leucocyte infiltration in sensitized guinea pigs, Immunopharmacology and immunotoxicology, doi:10.1081/iph-120029949

Khailany, Safdar, Ozaslan, Genomic characterization of a novel SARS-CoV-2, Gene reports, doi:10.1016/j.genrep.2020.100682

Kumari, g_mmpbsa-A GROMACS tool for high-throughput MM-PBSA calculations, Journal of chemical information and modeling, doi:10.1021/ci500020m

Lee, Richards, The interpretation of protein structures: estimation of static accessibility, J Mol Biol, doi:10.1016/0022-2836%2871%2990324-x

Li, Anti-virus effect of traditional Chinese medicine Yi-Fu-Qing granule on acute respiratory tract infections, Bioscience trends

Lin, Differentiation of cold and heat patterns: ambiguities in diagnosis, Clinical Acupuncture and Oriental Medicine

Liu, The relationship between cold-hot nature and nutrient contents of foods, Nutrition & Dietetics

Lockbaum, Crystal Structure of SARS-CoV-2 Main Protease in Complex with the Non-Covalent Inhibitor ML188, Viruses, doi:10.3390/v13020174

Ma, Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease, Cell research, doi:10.1038/s41422-020-0356-z

Ma, Bridging the gap between traditional Chinese medicine and systems biology: the connection of Cold Syndrome and NEI network, Molecular BioSystems, doi:10.1039/b914024g

Mojahedi, Reliability and validity assessment of Mizaj questionnaire: a novel self-report scale in Iranian traditional medicine

Monica, Targeting SARS-CoV-2 main protease for treatment of COVID-19: covalent inhibitors structure-activity relationship insights and evolution perspectives, Journal of medicinal chemistry, doi:10.1021/acs.jmedchem.2c01005

Pant, Peptide-like and small-molecule inhibitors against Covid-19, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2020.1757510

Park, The roles of phytochemicals in bronchial asthma, Molecules, doi:10.3390/molecules15106810

Parrinello, Rahman, Polymorphic transitions in single crystals: A new molecular dynamics method, Journal of Applied physics

Parvinroo, The effects of seeds with hot and cold temperaments on serum thyroid hormones, corticosterone and urine vanillylmandelic acid concentrations of healthy rats, Journal of Ethnopharmacology, doi:10.1016/j.jep.2014.08.026

Pettersen, UCSF Chimera-a visualization system for exploratory research and analysis, Journal of computational chemistry, doi:10.1002/jcc.20084

Ramphul, Mejias, Coronavirus disease: a review of a new threat to public health, Cureus, doi:10.7759/cureus.7276

Ren, The newly emerged SARS-like coronavirus HCoV-EMC also has an" Achilles' heel": current effective inhibitor targeting a 3C-like protease, Protein & cell, doi:10.1007/s13238-013-2841-3

Roodaki, Hot and cold: An old theory with modern applications, Trends in Pharmaceutical Sciences

Ryckaert, Ciccotti, Berendsen, Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes, Journal of computational physics

Ryu, Reliability and validity of a cold-heat pattern questionnaire for traditional Chinese medicine, The Journal of Alternative and Complementary Medicine, doi:10.1089/acm.2009.0331

Santos, Highly flexible ligand docking: Benchmarking of the DockThor program on the LEADS-PEP protein-peptide data set, Journal of Chemical Information and Modeling, doi:10.1021/acs.jcim.9b00905

Silvestrini, The dimer-monomer equilibrium of SARS-CoV-2 main protease is affected by small molecule inhibitors, Scientific Reports, doi:10.1038/s41598-021-88630-9

Ullrich, Nitsche, The SARS-CoV-2 main protease as drug target, Bioorganic & medicinal chemistry letters, doi:10.1016/j.bmcl.2020.127377

Vaidyanathan, News in focus, Nature

Vanommeslaeghe, Mackerell, Automation of the CHARMM General Force Field (CGenFF) I: bond perception and atom typing, Journal of chemical information and modeling

Vanommeslaeghe, Raman, Mackerell, Automation of the CHARMM General Force Field (CGenFF) II: assignment of bonded parameters and partial atomic charges, Journal of chemical information and modeling, doi:10.1021/ci3003649

Wallace, Laskowski, LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions, Protein engineering, design and selection, doi:10.1093/protein/8.2.127

Wang, Fast identification of possible drug treatment of coronavirus disease-19 (COVID-19) through computational drug repurposing study, Journal of chemical information and modeling, doi:10.1021/acs.jcim.0c00179

Wang, Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence, International journal of antimicrobial agents, doi:10.1016/j.ijantimicag.2020.105948

Wang, Structure of main protease from human coronavirus NL63: insights for wide spectrum anti-coronavirus drug design, Scientific reports, doi:10.1038/srep22677

Xiong, ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties, Nucleic Acids Res, doi:10.1093/nar/gkab255

Xue, Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design, Journal of virology, doi:10.1128/JVI.02114-07

Yang, Design of wide-spectrum inhibitors targeting coronavirus main proteases, PLoS biology, doi:10.1371/journal.pbio.0030324

Yang, Evolutionary and Structural Insights about Potential SARS-CoV-2 Evasion of Nirmatrelvir, J. Med. Chem, doi:10.1021/acs.jmedchem.2c00404

Zhang, Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors, Science

Zhang, HBD-2 binds SARS-CoV-2 RBD and blocks viral entry: Strategy to combat COVID-19, iScience, doi:10.1016/j.isci.2022.103856

Zhao, Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332, Protein & cell, doi:10.1007/s13238-021-00883-2

{ 'indexed': {'date-parts': [[2023, 12, 1]], 'date-time': '2023-12-01T00:32:49Z', 'timestamp': 1701390769979}, 'reference-count': 63, 'publisher': 'Public Library of Science (PLoS)', 'issue': '11', 'license': [ { 'start': { 'date-parts': [[2023, 11, 30]], 'date-time': '2023-11-30T00:00:00Z', 'timestamp': 1701302400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['www.plosone.org'], 'crossmark-restriction': False}, 'abstract': 'Main protease (Mpro) of SARS-CoV-2 is considered one of the key ' 'targets due to its role in viral replication. The use of traditional phytochemicals is an ' 'important part of complementary/alternative medicine, which also accompany the concept of ' 'temperament, where it has been shown that hot medicines cure cold and cold medicines cure ' 'hot, with cold and hot pattern being associated with oxidative and anti-oxidative properties ' 'in medicine, respectively. Molecular docking in this study has demonstrated that a number of ' 'anti-oxidative and hot temperament-based phytochemicals have high binding affinities to ' 'SARS-CoV-2 Mpro, both in the monomeric and dimeric deposited states of ' 'the protein. The highest ranking phytochemicals identified in this study included savinin, ' 'betulinic acid and curcumin. Complexes of savinin, betulinic acid, curcumin as well as ' 'Nirmatrelvir (the only approved inhibitor, used for comparison) bound to SARS-CoV-2 ' 'Mpro were further subjected to molecular dynamics simulations. ' 'Subsequently, RMSD, RMSF, Rg, number of hydrogen bonds, binding free energies and residue ' 'contributions (using MM-PBSA) and buried surface area (BSA), were analysed. The computational ' 'results suggested high binding affinities of savinin, betulinic acid and curcumin to both the ' 'monomeric and dimeric deposited states of Mpro, while highlighting the ' 'lower binding energy of betulinic acid in comparison with savinin and curcumin and even ' 'Nirmatrelvir, leading to a greater stability of the betulinic acid-SARS-CoV-2 ' 'Mpro complex. Overall, based on the increasing mutation rate in the ' 'spike protein and the fact that the SARS-CoV-2 Mpro remains highly ' 'conserved, this study provides an insight into the use of phytochemicals against COVID-19 and ' 'other coronavirus diseases.', 'DOI': '10.1371/journal.pone.0295014', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 11, 30]], 'date-time': '2023-11-30T18:54:48Z', 'timestamp': 1701370488000}, 'page': 'e0295014', 'update-policy': 'http://dx.doi.org/10.1371/journal.pone.corrections_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'In silico studies of anti-oxidative and hot temperament-based phytochemicals as natural ' 'inhibitors of SARS-CoV-2 Mpro', 'prefix': '10.1371', 'volume': '18', 'author': [ {'given': 'Ramin', 'family': 'Naderi Beni', 'sequence': 'first', 'affiliation': []}, {'given': 'Parisa', 'family': 'Elyasi-Ebli', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sajjad', 'family': 'Gharaghani', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-4234-9799', 'authenticated-orcid': True, 'given': 'Arefeh', 'family': 'Seyedarabi', 'sequence': 'additional', 'affiliation': []}], 'member': '340', 'published-online': {'date-parts': [[2023, 11, 30]]}, 'reference': [ { 'key': 'pone.0295014.ref001', 'volume-title': 'StatPearls', 'author': 'M Cascella', 'year': '2021'}, { 'issue': '3', 'key': 'pone.0295014.ref002', 'article-title': 'Coronavirus disease: a review of a new threat to public health', 'volume': '12', 'author': 'K. Ramphul', 'year': '2020', 'journal-title': 'Cureus'}, { 'issue': '6', 'key': 'pone.0295014.ref003', 'doi-asserted-by': 'crossref', 'first-page': '105948', 'DOI': '10.1016/j.ijantimicag.2020.105948', 'article-title': 'Review of the 2019 novel coronavirus (SARS-CoV-2) based on current ' 'evidence', 'volume': '55', 'author': 'L. Wang', 'year': '2020', 'journal-title': 'International journal of antimicrobial agents'}, { 'key': 'pone.0295014.ref004', 'unstructured': 'Available from: https://www.worldometers.info/coronavirus/.'}, { 'key': 'pone.0295014.ref005', 'doi-asserted-by': 'crossref', 'first-page': '100682', 'DOI': '10.1016/j.genrep.2020.100682', 'article-title': 'Genomic characterization of a novel SARS-CoV-2', 'volume': '19', 'author': 'R.A. Khailany', 'year': '2020', 'journal-title': 'Gene reports'}, { 'issue': '9', 'key': 'pone.0295014.ref006', 'doi-asserted-by': 'crossref', 'first-page': '689', 'DOI': '10.1007/s13238-021-00883-2', 'article-title': 'Crystal structure of SARS-CoV-2 main protease in complex with protease ' 'inhibitor PF-07321332', 'volume': '13', 'author': 'Y. Zhao', 'year': '2022', 'journal-title': 'Protein & cell'}, { 'issue': '17', 'key': 'pone.0295014.ref007', 'doi-asserted-by': 'crossref', 'first-page': '127377', 'DOI': '10.1016/j.bmcl.2020.127377', 'article-title': 'The SARS-CoV-2 main protease as drug target', 'volume': '30', 'author': 'S. Ullrich', 'year': '2020', 'journal-title': 'Bioorganic & medicinal chemistry letters'}, { 'issue': '5626', 'key': 'pone.0295014.ref008', 'doi-asserted-by': 'crossref', 'first-page': '1763', 'DOI': '10.1126/science.1085658', 'article-title': 'Coronavirus main proteinase (3CLpro) structure: basis for design of ' 'anti-SARS drugs', 'volume': '300', 'author': 'K. Anand', 'year': '2003', 'journal-title': 'Science'}, { 'issue': '19', 'key': 'pone.0295014.ref009', 'doi-asserted-by': 'crossref', 'first-page': '12500', 'DOI': '10.1021/acs.jmedchem.2c01005', 'article-title': 'Targeting SARS-CoV-2 main protease for treatment of COVID-19: covalent ' 'inhibitors structure–activity relationship insights and evolution ' 'perspectives', 'volume': '65', 'author': 'G. La Monica', 'year': '2022', 'journal-title': 'Journal of medicinal chemistry'}, { 'issue': '7811', 'key': 'pone.0295014.ref010', 'doi-asserted-by': 'crossref', 'first-page': '289', 'DOI': '10.1038/s41586-020-2223-y', 'article-title': 'Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors', 'volume': '582', 'author': 'Z. Jin', 'year': '2020', 'journal-title': 'Nature'}, { 'issue': '6489', 'key': 'pone.0295014.ref011', 'doi-asserted-by': 'crossref', 'first-page': '409', 'DOI': '10.1126/science.abb3405', 'article-title': 'Crystal structure of SARS-CoV-2 main protease provides a basis for ' 'design of improved α-ketoamide inhibitors', 'volume': '368', 'author': 'L. Zhang', 'year': '2020', 'journal-title': 'Science'}, { 'issue': '1', 'key': 'pone.0295014.ref012', 'doi-asserted-by': 'crossref', 'first-page': '9283', 'DOI': '10.1038/s41598-021-88630-9', 'article-title': 'The dimer-monomer equilibrium of SARS-CoV-2 main protease is affected ' 'by small molecule inhibitors', 'volume': '11', 'author': 'L. Silvestrini', 'year': '2021', 'journal-title': 'Scientific Reports'}, { 'issue': '1', 'key': 'pone.0295014.ref013', 'doi-asserted-by': 'crossref', 'first-page': '113', 'DOI': '10.1081/IPH-120029949', 'article-title': 'Effects of Ding‐Chuan‐Tang on bronchoconstriction and airway leucocyte ' 'infiltration in sensitized guinea pigs', 'volume': '26', 'author': 'S.T. Kao', 'year': '2004', 'journal-title': 'Immunopharmacology and immunotoxicology'}, { 'issue': '4', 'key': 'pone.0295014.ref014', 'first-page': '119', 'article-title': 'Anti-virus effect of traditional Chinese medicine Yi-Fu-Qing granule on ' 'acute respiratory tract infections', 'volume': '3', 'author': 'A. Li', 'year': '2009', 'journal-title': 'Bioscience trends'}, { 'issue': '10', 'key': 'pone.0295014.ref015', 'doi-asserted-by': 'crossref', 'first-page': '6810', 'DOI': '10.3390/molecules15106810', 'article-title': 'The roles of phytochemicals in bronchial asthma', 'volume': '15', 'author': 'H.S. Park', 'year': '2010', 'journal-title': 'Molecules'}, { 'issue': '1', 'key': 'pone.0295014.ref016', 'doi-asserted-by': 'crossref', 'first-page': '93', 'DOI': '10.1093/ajcn/76.1.93', 'article-title': 'Fruit and vegetable intake and risk of cardiovascular disease in US ' 'adults: the first National Health and Nutrition Examination Survey ' 'Epidemiologic Follow-up Study', 'volume': '76', 'author': 'L.A. Bazzano', 'year': '2002', 'journal-title': 'The American journal of clinical nutrition'}, { 'issue': '1', 'key': 'pone.0295014.ref017', 'article-title': 'Hot and cold: An old theory with modern applications', 'volume': '4', 'author': 'M. Roodaki', 'year': '2018', 'journal-title': 'Trends in Pharmaceutical Sciences'}, { 'key': 'pone.0295014.ref018', 'author': 'M. Mojahedi', 'year': '2014', 'journal-title': 'Reliability and validity assessment of Mizaj questionnaire: a novel ' 'self-report scale in Iranian traditional medicine'}, { 'key': 'pone.0295014.ref019', 'doi-asserted-by': 'crossref', 'first-page': '216', 'DOI': '10.1016/j.jep.2014.08.026', 'article-title': 'The effects of seeds with hot and cold temperaments on serum thyroid ' 'hormones, corticosterone and urine vanillylmandelic acid concentrations ' 'of healthy rats', 'volume': '156', 'author': 'S. Parvinroo', 'year': '2014', 'journal-title': 'Journal of Ethnopharmacology'}, { 'issue': '3', 'key': 'pone.0295014.ref020', 'doi-asserted-by': 'crossref', 'first-page': '145', 'DOI': '10.4077/CJP.2011.AMM045', 'article-title': 'Effects of hot and cold foods on signals of heart rate variability and ' 'nail fold microcirculation of healthy young humans: a pilot study', 'volume': '54', 'author': 'D.-P. Chao', 'year': '2011', 'journal-title': 'Chinese Journal of Physiology'}, { 'issue': '2', 'key': 'pone.0295014.ref021', 'doi-asserted-by': 'crossref', 'first-page': '102', 'DOI': '10.1054/caom.2001.0082', 'article-title': 'Differentiation of cold and heat patterns: ambiguities in diagnosis', 'volume': '2', 'author': 'Y.S. Lin', 'year': '2001', 'journal-title': 'Clinical Acupuncture and Oriental Medicine'}, { 'issue': '4', 'key': 'pone.0295014.ref022', 'doi-asserted-by': 'crossref', 'first-page': '613', 'DOI': '10.1039/b914024g', 'article-title': 'Bridging the gap between traditional Chinese medicine and systems ' 'biology: the connection of Cold Syndrome and NEI network', 'volume': '6', 'author': 'T. Ma', 'year': '2010', 'journal-title': 'Molecular BioSystems'}, { 'issue': '6', 'key': 'pone.0295014.ref023', 'doi-asserted-by': 'crossref', 'first-page': '663', 'DOI': '10.1089/acm.2009.0331', 'article-title': 'Reliability and validity of a cold–heat pattern questionnaire for ' 'traditional Chinese medicine', 'volume': '16', 'author': 'H. Ryu', 'year': '2010', 'journal-title': 'The Journal of Alternative and Complementary Medicine'}, { 'key': 'pone.0295014.ref024', 'first-page': '1', 'article-title': 'Is the Iranian Traditional Medicine warm and cold temperament related ' 'to Basal Metabolic Rate and activity of the sympathetic-parasympathetic ' 'system?', 'volume': '13', 'author': 'G.M. Farsani', 'year': '2014', 'journal-title': 'Study protocol. Journal of Diabetes & Metabolic Disorders'}, { 'issue': '1', 'key': 'pone.0295014.ref025', 'doi-asserted-by': 'crossref', 'first-page': '64', 'DOI': '10.1111/j.1747-0080.2011.01565.x', 'article-title': 'The relationship between cold‐hot nature and nutrient contents of ' 'foods.', 'volume': '69', 'author': 'C. Liu', 'year': '2012', 'journal-title': 'Nutrition & Dietetics'}, { 'issue': '4', 'key': 'pone.0295014.ref026', 'first-page': '462', 'article-title': 'The Relationship between the Severity of the COVID-19 ' 'DiseaseTemperament and Psychological Factors.', 'volume': '17', 'author': 'A. Afzali', 'year': '2022', 'journal-title': 'Iranian Journal of Psychiatry'}, { 'issue': '13', 'key': 'pone.0295014.ref027', 'doi-asserted-by': 'crossref', 'first-page': '8686', 'DOI': '10.1021/acs.jmedchem.2c00404', 'article-title': 'Evolutionary and Structural Insights about Potential SARS-CoV-2 Evasion ' 'of Nirmatrelvir', 'volume': '65', 'author': 'K.S. Yang', 'year': '2022', 'journal-title': 'J. Med. Chem.'}, { 'key': 'pone.0295014.ref028', 'doi-asserted-by': 'crossref', 'first-page': '101646', 'DOI': '10.1016/j.tmaid.2020.101646', 'article-title': 'A search for medications to treat COVID-19 via in silico molecular ' 'docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease', 'volume': '35', 'author': 'D.C. Hall', 'year': '2020', 'journal-title': 'Travel medicine and infectious disease'}, { 'issue': '9', 'key': 'pone.0295014.ref029', 'first-page': '3387', 'article-title': 'Using integrated computational approaches to identify safe and rapid ' 'treatment for SARS-CoV-2', 'volume': '39', 'author': 'K. Al-Khafaji', 'year': '2021', 'journal-title': 'Journal of Biomolecular Structure and Dynamics'}, { 'issue': '8', 'key': 'pone.0295014.ref030', 'doi-asserted-by': 'crossref', 'first-page': '2904', 'DOI': '10.1080/07391102.2020.1757510', 'article-title': 'Peptide-like and small-molecule inhibitors against Covid-19', 'volume': '39', 'author': 'S. Pant', 'year': '2021', 'journal-title': 'Journal of Biomolecular Structure and Dynamics'}, { 'issue': '6', 'key': 'pone.0295014.ref031', 'doi-asserted-by': 'crossref', 'first-page': '3277', 'DOI': '10.1021/acs.jcim.0c00179', 'article-title': 'Fast identification of possible drug treatment of coronavirus ' 'disease-19 (COVID-19) through computational drug repurposing study', 'volume': '60', 'author': 'J. Wang', 'year': '2020', 'journal-title': 'Journal of chemical information and modeling'}, { 'key': 'pone.0295014.ref032', 'doi-asserted-by': 'crossref', 'first-page': '117627', 'DOI': '10.1016/j.lfs.2020.117627', 'article-title': 'Virtual screening and repurposing of FDA approved drugs against ' 'COVID-19 main protease', 'volume': '251', 'author': 'M. Kandeel', 'year': '2020', 'journal-title': 'Life sciences'}, { 'issue': '2', 'key': 'pone.0295014.ref033', 'doi-asserted-by': 'crossref', 'first-page': '159', 'DOI': '10.2478/acph-2022-0020', 'article-title': 'Promising inhibitors against main protease of SARS CoV-2 from medicinal ' 'plants: In silico identification', 'volume': '72', 'author': 'O. Ebenezer', 'year': '2022', 'journal-title': 'Acta Pharmaceutica'}, { 'issue': '9', 'key': 'pone.0295014.ref034', 'doi-asserted-by': 'crossref', 'first-page': '2654', 'DOI': '10.3390/molecules26092654', 'article-title': 'Olive-derived triterpenes suppress SARS COV-2 main protease: a ' 'promising scaffold for future therapeutics', 'volume': '26', 'author': 'H.A. Alhadrami', 'year': '2021', 'journal-title': 'Molecules'}, { 'issue': '2', 'key': 'pone.0295014.ref035', 'doi-asserted-by': 'crossref', 'first-page': '174', 'DOI': '10.3390/v13020174', 'article-title': 'Crystal Structure of SARS-CoV-2 Main Protease in Complex with the ' 'Non-Covalent Inhibitor ML188', 'volume': '13', 'author': 'G.J. Lockbaum', 'year': '2021', 'journal-title': 'Viruses'}, { 'issue': 'W1', 'key': 'pone.0295014.ref036', 'doi-asserted-by': 'crossref', 'first-page': 'W5', 'DOI': '10.1093/nar/gkab255', 'article-title': 'ADMETlab 2.0: an integrated online platform for accurate and ' 'comprehensive predictions of ADMET properties', 'volume': '49', 'author': 'G. Xiong', 'year': '2021', 'journal-title': 'Nucleic Acids Res.'}, { 'issue': '18', 'key': 'pone.0295014.ref037', 'doi-asserted-by': 'crossref', 'first-page': '10037', 'DOI': '10.1073/pnas.181342398', 'article-title': 'Electrostatics of nanosystems: Application to microtubules and the ' 'ribosome.', 'volume': '98', 'author': 'N. Baker', 'year': '2001', 'journal-title': 'Proceedings of the National Academy of Sciences'}, { 'issue': '7', 'key': 'pone.0295014.ref038', 'doi-asserted-by': 'crossref', 'first-page': '1951', 'DOI': '10.1021/ci500020m', 'article-title': 'g_mmpbsa—A GROMACS tool for high-throughput MM-PBSA calculations', 'volume': '54', 'author': 'R. Kumari', 'year': '2014', 'journal-title': 'Journal of chemical information and modeling'}, { 'issue': '3', 'key': 'pone.0295014.ref039', 'doi-asserted-by': 'crossref', 'first-page': '103856', 'DOI': '10.1016/j.isci.2022.103856', 'article-title': 'HBD-2 binds SARS-CoV-2 RBD and blocks viral entry: Strategy to combat ' 'COVID-19', 'volume': '25', 'author': 'L. Zhang', 'year': '2022', 'journal-title': 'iScience'}, { 'issue': '7873', 'key': 'pone.0295014.ref040', 'doi-asserted-by': 'crossref', 'first-page': '472', 'DOI': '10.1038/d41586-021-02275-2', 'article-title': 'The mutation that helps Delta spread like wildfire', 'volume': '596', 'author': 'E. Callaway', 'year': '2021', 'journal-title': 'Nature'}, { 'key': 'pone.0295014.ref041', 'first-page': '321', 'article-title': 'News in focus', 'volume': '593', 'author': 'G. Vaidyanathan', 'year': '2021', 'journal-title': '. Nature'}, { 'issue': '2', 'key': 'pone.0295014.ref042', 'doi-asserted-by': 'crossref', 'first-page': '127', 'DOI': '10.1093/protein/8.2.127', 'article-title': 'LIGPLOT: a program to generate schematic diagrams of protein-ligand ' 'interactions', 'volume': '8', 'author': 'A.C. Wallace', 'year': '1995', 'journal-title': 'Protein engineering, design and selection'}, { 'issue': '1', 'key': 'pone.0295014.ref043', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1038/s41598-021-82410-1', 'article-title': 'New machine learning and physics-based scoring functions for drug ' 'discovery', 'volume': '11', 'author': 'I.A. Guedes', 'year': '2021', 'journal-title': 'Scientific reports'}, { 'issue': '2', 'key': 'pone.0295014.ref044', 'doi-asserted-by': 'crossref', 'first-page': '667', 'DOI': '10.1021/acs.jcim.9b00905', 'article-title': 'Highly flexible ligand docking: Benchmarking of the DockThor program on ' 'the LEADS-PEP protein–peptide data set', 'volume': '60', 'author': 'K.B. Santos', 'year': '2020', 'journal-title': 'Journal of Chemical Information and Modeling'}, { 'key': 'pone.0295014.ref045', 'doi-asserted-by': 'crossref', 'first-page': '206', 'DOI': '10.1016/j.ins.2014.08.002', 'article-title': 'A dynamic niching genetic algorithm strategy for docking highly ' 'flexible ligands', 'volume': '289', 'author': 'C.S. de Magalhães', 'year': '2014', 'journal-title': 'Information Sciences'}, { 'issue': '10', 'key': 'pone.0295014.ref046', 'doi-asserted-by': 'crossref', 'first-page': 'e324', 'DOI': '10.1371/journal.pbio.0030324', 'article-title': 'Design of wide-spectrum inhibitors targeting coronavirus main proteases', 'volume': '3', 'author': 'H. Yang', 'year': '2005', 'journal-title': 'PLoS biology'}, { 'issue': '5', 'key': 'pone.0295014.ref047', 'doi-asserted-by': 'crossref', 'first-page': '2515', 'DOI': '10.1128/JVI.02114-07', 'article-title': 'Structures of two coronavirus main proteases: implications for ' 'substrate binding and antiviral drug design', 'volume': '82', 'author': 'X. Xue', 'year': '2008', 'journal-title': 'Journal of virology'}, { 'issue': '4', 'key': 'pone.0295014.ref048', 'doi-asserted-by': 'crossref', 'first-page': '248', 'DOI': '10.1007/s13238-013-2841-3', 'article-title': 'The newly emerged SARS-like coronavirus HCoV-EMC also has an" Achilles’ ' 'heel": current effective inhibitor targeting a 3C-like protease', 'volume': '4', 'author': 'Z. Ren', 'year': '2013', 'journal-title': '. Protein & cell'}, { 'issue': '1', 'key': 'pone.0295014.ref049', 'doi-asserted-by': 'crossref', 'first-page': '22677', 'DOI': '10.1038/srep22677', 'article-title': 'Structure of main protease from human coronavirus NL63: insights for ' 'wide spectrum anti-coronavirus drug design', 'volume': '6', 'author': 'F. Wang', 'year': '2016', 'journal-title': 'Scientific reports'}, { 'issue': '8', 'key': 'pone.0295014.ref050', 'doi-asserted-by': 'crossref', 'first-page': '678', 'DOI': '10.1038/s41422-020-0356-z', 'article-title': 'Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 ' 'viral replication by targeting the viral main protease', 'volume': '30', 'author': 'C. Ma', 'year': '2020', 'journal-title': 'Cell research'}, { 'issue': '6497', 'key': 'pone.0295014.ref051', 'doi-asserted-by': 'crossref', 'first-page': '1331', 'DOI': '10.1126/science.abb4489', 'article-title': 'Structure-based design of antiviral drug candidates targeting the ' 'SARS-CoV-2 main protease', 'volume': '368', 'author': 'W. Dai', 'year': '2020', 'journal-title': 'Science'}, { 'issue': '13', 'key': 'pone.0295014.ref052', 'doi-asserted-by': 'crossref', 'first-page': '1605', 'DOI': '10.1002/jcc.20084', 'article-title': 'UCSF Chimera—a visualization system for exploratory research and ' 'analysis', 'volume': '25', 'author': 'E.F. Pettersen', 'year': '2004', 'journal-title': 'Journal of computational chemistry'}, { 'key': 'pone.0295014.ref053', 'doi-asserted-by': 'crossref', 'first-page': '19', 'DOI': '10.1016/j.softx.2015.06.001', 'article-title': 'GROMACS: High performance molecular simulations through multi-level ' 'parallelism from laptops to supercomputers', 'volume': '1', 'author': 'M.J. Abraham', 'year': '2015', 'journal-title': 'SoftwareX'}, { 'issue': '25', 'key': 'pone.0295014.ref054', 'doi-asserted-by': 'crossref', 'first-page': '2135', 'DOI': '10.1002/jcc.23354', 'article-title': 'CHARMM36 all‐atom additive protein force field: Validation based on ' 'comparison to NMR data', 'volume': '34', 'author': 'J. Huang', 'year': '2013', 'journal-title': 'Journal of computational chemistry'}, { 'issue': '12', 'key': 'pone.0295014.ref055', 'first-page': '3144', 'volume': '52', 'author': 'K. Vanommeslaeghe', 'year': '2012', 'journal-title': 'Automation of the CHARMM General Force Field (CGenFF) I: bond ' 'perception and atom typing. Journal of chemical information and ' 'modeling'}, { 'issue': '12', 'key': 'pone.0295014.ref056', 'doi-asserted-by': 'crossref', 'first-page': '3155', 'DOI': '10.1021/ci3003649', 'article-title': 'Automation of the CHARMM General Force Field (CGenFF) II: assignment of ' 'bonded parameters and partial atomic charges', 'volume': '52', 'author': 'K. Vanommeslaeghe', 'year': '2012', 'journal-title': 'Journal of chemical information and modeling'}, { 'issue': '2', 'key': 'pone.0295014.ref057', 'doi-asserted-by': 'crossref', 'first-page': '926', 'DOI': '10.1063/1.445869', 'article-title': 'Comparison of simple potential functions for simulating liquid water', 'volume': '79', 'author': 'W.L. Jorgensen', 'year': '1983', 'journal-title': 'The Journal of chemical physics'}, { 'key': 'pone.0295014.ref058', 'doi-asserted-by': 'crossref', 'first-page': '401', 'DOI': '10.1007/BF00941484', 'article-title': 'A steepest-descent method for optimization of mechanical systems', 'volume': '19', 'author': 'E. Haug', 'year': '1976', 'journal-title': 'Journal of Optimization Theory and Applications'}, { 'issue': '8', 'key': 'pone.0295014.ref059', 'doi-asserted-by': 'crossref', 'first-page': '3684', 'DOI': '10.1063/1.448118', 'article-title': 'Molecular dynamics with coupling to an external bath', 'volume': '81', 'author': 'H.J. Berendsen', 'year': '1984', 'journal-title': 'The Journal of chemical physics'}, { 'issue': '12', 'key': 'pone.0295014.ref060', 'doi-asserted-by': 'crossref', 'first-page': '7182', 'DOI': '10.1063/1.328693', 'article-title': 'Polymorphic transitions in single crystals: A new molecular dynamics ' 'method', 'volume': '52', 'author': 'M. Parrinello', 'year': '1981', 'journal-title': 'Journal of Applied physics'}, { 'issue': '3', 'key': 'pone.0295014.ref061', 'doi-asserted-by': 'crossref', 'first-page': '327', 'DOI': '10.1016/0021-9991(77)90098-5', 'article-title': 'Numerical integration of the cartesian equations of motion of a system ' 'with constraints: molecular dynamics of n-alkanes', 'volume': '23', 'author': 'J.-P. Ryckaert', 'year': '1977', 'journal-title': 'Journal of computational physics'}, { 'key': 'pone.0295014.ref062', 'doi-asserted-by': 'crossref', 'first-page': '33', 'DOI': '10.1016/0263-7855(96)00018-5', 'article-title': 'VMD—Visual Molecular Dynamics', 'volume': '14', 'author': 'W. Humphrey', 'year': '1996', 'journal-title': 'J. Molec. Graphics'}, { 'issue': '3', 'key': 'pone.0295014.ref063', 'doi-asserted-by': 'crossref', 'first-page': '379', 'DOI': '10.1016/0022-2836(71)90324-X', 'article-title': 'The interpretation of protein structures: estimation of static ' 'accessibility', 'volume': '55', 'author': 'B. Lee', 'year': '1971', 'journal-title': 'J Mol Biol.'}], 'container-title': 'PLOS ONE', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://dx.plos.org/10.1371/journal.pone.0295014', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 11, 30]], 'date-time': '2023-11-30T18:55:24Z', 'timestamp': 1701370524000}, 'score': 1, 'resource': {'primary': {'URL': 'https://dx.plos.org/10.1371/journal.pone.0295014'}}, 'subtitle': [], 'editor': [{'given': 'Ahmed A.', 'family': 'Al-Karmalawy', 'sequence': 'first', 'affiliation': []}], 'short-title': [], 'issued': {'date-parts': [[2023, 11, 30]]}, 'references-count': 63, 'journal-issue': {'issue': '11', 'published-online': {'date-parts': [[2023, 11, 30]]}}, 'URL': 'http://dx.doi.org/10.1371/journal.pone.0295014', 'relation': {}, 'ISSN': ['1932-6203'], 'subject': ['Multidisciplinary'], 'container-title-short': 'PLoS ONE', 'published': {'date-parts': [[2023, 11, 30]]}}

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