All Studies Meta Analysis

New findings on ligand series used as SARS-CoV-2 virus inhibitors within the frameworks of molecular docking, molecular quantum similarity and chemical reactivity indices

Morales-Bayuelo et al., F1000Research, doi:10.12688/f1000research.123550.3

Dec 2023

Post
Facebook

Source PDF All Studies Meta AnalysisMeta

Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.

Lower risk for mortality, ICU admission, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine treatments.

5,100+ studies for 109 treatments. c19early.org

In Silico analysis showing that cholecalciferol (vitamin D3) binds to the SARS-CoV-2 RNA-dependent RNA polymerase active site. Favorable stabilizing interactions were predicted, including hydrogen bonding with residues serine 759, glutamic acid 166, and tryptophan 617. The binding affinity was significant enough to generate a defined binding pocket contour matching other proven COVID-19 medication candidates.

21 preclinical studies support the efficacy of vitamin D for COVID-19:

7 In Silico studies1-7

11 In Vitro studies8-18

3 In Vivo animal studies10,14,19

Vitamin D has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function20-23. Vitamin D inhibits SARS-CoV-2 replication in vitro10,17, mitigates lung inflammation, damage, and lethality in mice with an MHV-3 model for β-CoV respiratory infections10,17, reduces SARS-CoV-2 replication in nasal epithelial cells via increased type I interferon expression13, downregulates proinflammatory cytokines IL-1β and TNF-α in SARS-CoV-2 spike protein-stimulated cells9, attenuates nucleocapsid protein-induced hyperinflammation by inactivating the NLRP3 inflammasome through the VDR-BRCC3 signaling pathway14, may be neuroprotective by protecting the blood-brain barrier, reducing neuroinflammation, and via immunomodulatory effects24, downregulates ACE2 and TMPRSS2 in human trophoblasts and minimizes spike protein-induced inflammation12, minimizes platelet aggregation mediated by SARS-CoV-2 spike protein via inhibiting integrin αIIbβ3 outside-in signaling8, and improves regulatory immune cell levels and control of proinflammatory cytokines in severe COVID-1925. Symptomatic COVID-19 is associated with a lower frequency of natural killer (NK) cells and vitamin D has been shown to improve NK cell activity26,27.

Important missing comments or errors? Let us know.

Study covers vitamin D and vitamin C.

1. Morales-Bayuelo et al., New findings on ligand series used as SARS-CoV-2 virus inhibitors within the frameworks of molecular docking, molecular quantum similarity and chemical reactivity indices, F1000Research, doi:10.12688/f1000research.123550.3.f1000research.com, doi.org.

2. Chellasamy et al., Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors, Journal of King Saud University - Science, doi:10.1016/j.jksus.2022.102277.sciencedirect.com, doi.org.

3. Pandya et al., Unravelling Vitamin B12 as a potential inhibitor against SARS-CoV-2: A computational approach, Informatics in Medicine Unlocked, doi:10.1016/j.imu.2022.100951.sciencedirect.com, doi.org.

4. Mansouri et al., The impact of calcitriol and estradiol on the SARS-CoV-2 biological activity: a molecular modeling approach, Scientific Reports, doi:10.1038/s41598-022-04778-y.nature.com, doi.org.

5. Song et al., Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1964601.tandfonline.com, doi.org.

6. Qayyum et al., Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 replication machinery enzymes, Endocrinology and Metabolism, doi:10.1152/ajpendo.00174.2021.physiology.org, doi.org.

7. Al-Mazaideh et al., Vitamin D is a New Promising Inhibitor to the Main Protease (Mpro) of COVID-19 by Molecular Docking, Journal of Pharmaceutical Research International, doi:10.9734/jpri/2021/v33i29B31603.journaljpri.com, doi.org.

8. Wang et al., 1,25‐Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS‐CoV‐2 spike protein via inhibiting integrin αIIbβ3 outside‐in signaling, Cell Biochemistry and Function, doi:10.1002/cbf.4039.wiley.com, doi.org.

9. Alcalá-Santiago et al., Disentangling the Immunomodulatory Effects of Vitamin D on the SARS-CoV-2 Virus by In Vitro Approaches, The 14th European Nutrition Conference FENS 2023, doi:10.3390/proceedings2023091415.mdpi.com, doi.org.

10. Campolina-Silva et al., Dietary Vitamin D Mitigates Coronavirus-Induced Lung Inflammation and Damage in Mice, Viruses, doi:10.3390/v15122434.mdpi.com, doi.org.

11. Moatasim et al., Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E, Microorganisms, doi:10.3390/microorganisms11112777.mdpi.com, doi.org.

12. Vargas-Castro et al., Calcitriol prevents SARS-CoV spike-induced inflammation in human trophoblasts through downregulating ACE2 and TMPRSS2 expression, The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2024.106625.sciencedirect.com, doi.org.

13. Sposito et al., Age differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - effects of vitamin D, Mucosal Immunology, doi:10.1016/j.mucimm.2023.08.002.nih.gov, doi.org.

14. Chen et al., Vitamin D3 attenuates SARS‐CoV‐2 nucleocapsid protein‐caused hyperinflammation by inactivating the NLRP3 inflammasome through the VDR‐BRCC3 signaling pathway in vitro and in vivo, MedComm, doi:10.1002/mco2.318.wiley.com, doi.org.

15. Rybakovsky et al., Calcitriol modifies tight junctions, improves barrier function, and reduces TNF‐α‐induced barrier leak in the human lung‐derived epithelial cell culture model, 16HBE 14o‐, Physiological Reports, doi:10.14814/phy2.15592.wiley.com, doi.org.

16. DiGuilio et al., The multiphasic TNF-α-induced compromise of Calu-3 airway epithelial barrier function, Experimental Lung Research, doi:10.1080/01902148.2023.2193637.tandfonline.com, doi.org.

17. Pickard et al., Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells, PLOS Pathogens, doi:10.1371/journal.ppat.1009840.plos.org, doi.org.

18. Mok et al., Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis, bioRxiv, doi:10.1101/2020.06.21.162396.biorxiv.org, doi.org.

19. Fernandes de Souza et al., Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D, Cells, doi:10.3390/cells12071092.mdpi.com, doi.org.

20. Galmés et al., Suboptimal Consumption of Relevant Immune System Micronutrients Is Associated with a Worse Impact of COVID-19 in Spanish Populations, Nutrients, doi:10.3390/nu14112254.mdpi.com, doi.org.

21. Galmés (B) et al., Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework, Nutrients, doi:10.3390/nu12092738.mdpi.com, doi.org.

22. EFSA, Scientific Opinion on the substantiation of a health claim related to vitamin D and contribution to the normal function of the immune system pursuant to Article 14 of Regulation (EC) No 1924/2006, EFSA Journal, doi:10.2903/j.efsa.2015.4096.europa.eu, doi.org.

23. EFSA (B), Scientific Opinion on the substantiation of health claims related to vitamin D and normal function of the immune system and inflammatory response (ID 154, 159), maintenance of normal muscle function (ID 155) and maintenance of normal cardiovascular function (ID 159) pursuant to Article 13(1) of Regulation (E, EFSA Journal, doi:10.2903/j.efsa.2010.1468.wiley.com, doi.org.

24. Gotelli et al., Understanding the immune-endocrine effects of vitamin D in SARS-CoV-2 infection: a role in protecting against neurodamage?, Neuroimmunomodulation, doi:10.1159/000533286.karger.com, doi.org.

25. Saheb Sharif-Askari et al., Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons, Scientific Reports, doi:10.1038/s41598-023-43675-w.nature.com, doi.org.

26. Graydon et al., High baseline frequencies of natural killer cells are associated with asymptomatic SARS-CoV-2 infection, Current Research in Immunology, doi:10.1016/j.crimmu.2023.100064.sciencedirect.com, doi.org.

27. Oh et al., Vitamin D and Exercise Are Major Determinants of Natural Killer Cell Activity, Which Is Age- and Gender-Specific, Frontiers in Immunology, doi:10.3389/fimmu.2021.594356.frontiersin.org, doi.org.

Morales-Bayuelo et al., 11 Dec 2023, peer-reviewed, 2 authors. Contact: amorales@unisinucartagena.edu.co.

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

This Paper Vitamin D All

New findings on ligand series used as SARS-CoV-2 virus inhibitors within the frameworks of molecular docking, molecular quantum similarity and chemical reactivity indices

Alejandro Morales-Bayuelo, Jesús Sánchez-Márquez

F1000Research, doi:10.12688/f1000research.123550.1

Background The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus causes an infectious illness named coronavirus disease 2019 (COVID-19). SARS-CoV is a positive-sense single-stranded RNA virus from the Betacoronavirus genus. The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has an important role in the viral life cycle and its active site is a very accessible region, thus a potential therapeutic approach may be to target this region to study the inhibition of viral replication. Various preexisting drugs have been proposed for the treatment of COVID-19 and the use of existing antiviral agents may reduce the time and cost of new drug discoveries, but the efficacy of these drugs is limited. Therefore, the aim of the present study was to evaluate a number of ligands used as SARS-CoV-2 virus inhibitors to determine the suitability of them for potential COVID-19 treatment. Methods In this study, we selected a series of ligands used as SARS-CoV-2 virus inhibitors such as: abacavir, acyclovir, amprenavir, ascorbic acid vitamin C, azithromycin, baloxavir, boceprevir, cholecalciferol vitamin D, cidofovir, edoxudine, emtricitabine, hydroxychloroquine and

Open Peer Review Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Computational chemistry; DFT; Nanotechnology; Docking simulation I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Author Response 17 Jul 2023 Alejandro Morales-Bayuelo 1. What are the novelties of the manuscript? What's new in this manuscript compared to similar papers? Answer: There is currently no effective treatment for Covid-19. Therefore, there are a series of drugs such as those listed in this article that have been used for the treatment of this disease, however they have not been associated as solutions for covid-19. That is why carrying out studies that show that the drugs used are directly related to the Covid-19 proteins is pertinent. 2. The introduction section should be written in a higher quality way, i.e. more up-to-date references. The..

References

Abdrabbo, Birch, Brandt, Vitamin D and COVID-19: A review on the role of vitamin D in preventing and reducing the severity of COVID-19 infection, Protein Sci, doi:10.1002/pro.4190

Adamsick, Gandhi, Bidell, Remdesivir in patients with acute or chronic kidney disease and COVID-19, J. Am. Soc

Amat, Carbó-Dorca, Quantum similarity measures under atomic shell approximation: First order density fitting using elementary Jacobi rotations, J. Comput. Chem, doi:10.1002/(SICI)1096-987X(199712)18:162023::AID-JCC73.0.CO;2-N

Bultinck, Gironés, Carbó-Dorca, Molecular quantum similarity using conceptual DFT descriptors, Rev. Comput. Chem, doi:10.1002/0471720895.ch2

Burley, Berman, Bhikadiya, RCSB Protein Data Bank: Biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy, Nucleic Acids Res, doi:10.1093/nar/gky1004

Carbó-Dorca, Amat, Besalú, Quantum Similarity. Advanced Molecular Similarity

Carbó-Dorca, Amat, Besalú, Quantum mechanical origin of QSAR: theory and applications, J. Mol. Struct. THEOCHEM, doi:10.1016/S0166-1280(00)00363-8

Carbó-Dorca, Gironés, Foundation of quantum similarity measures and their relationship to QSPR: density function structure, approximations, and application examples, Int. J. Quantum Chem, doi:10.1002/qua.20191

Carbó-Dorca, Leyda, Arnau, How Similar is a Molecule to Another? An Electron Density Measure of Similarity Between Two Molecular Structures, Int. J. Quantum Chem, doi:10.1002/qua.560170612

Chattaraj, Sarkar, Roy, Electrophilicity index, Chem. Rev, doi:10.1021/cr040109f

Constans, Amat, Carbó-Dorca, Tagged sets, convex sets and quantum similarity measures, J. Comput. Chem, doi:10.1002/(SICI)1096-987X(19970430)18:6826::AID-JCC83.0.CO;2-U

Constans, Carbo, Atomic shell approximation: electron density fitting algorithm restricting coefficients to positive values, J. Chem. Inf. Comput. Sci

Elfiky, SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: an in silico perspective, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1761882

Emili, Xavier, Amat, Molecular Quantum Similarity and the Fundamentals of QSAR, Acc. Chem. Res, doi:10.1021/ar010048x

Friesner, Banks, Murphy, Glide: A New Approach for Rapid, Accurate Docking and Scor-ing. 1. Method and Assessment of Docking Accuracy, J. Med. Chem, doi:10.1021/jm0306430

Frisch, Trucks, Schlegel, Gaussian Inc

Fuentealba, Pérez, Contreras, On the Condensed Fukui Function, J. Chem. Phys, doi:10.1063/1.1305879

Galván, Pérez, Contreras, A direct evaluation of regional Fukui functions in molecules, Chem. Phys. Lett

Geerlings, Proft, Langenaeker, Conceptual density functional theory, Chem. Rev, doi:10.1021/cr990029p

Hagar, Ahmed, Aljohani, Investigation of Some Antiviral N-Heterocycles as COVID 19 Drug: Molecular Docking and DFT Calculations, Int. J. Mol. Sci, doi:10.3390/ijms21113922

Halgren, Mainz, Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking Accuracy, J. Med. Chem, doi:10.1021/jm0306430

Jorgensen, Maxwell, Tirado-Rives, Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids, J. Am. Chem. Soc, doi:10.1021/ja9621760

Morales-Bayuelo, Baldiris, Vivas-Reyes, Scale Alpha and Beta of Quantitative Convergence and Chemical Reactivity Analysis in Dual Cholinesterase/Monoamine Oxidase Inhibitors for the Alzheimer Disease Treatment using Density Functional Theory (DFT), J. Theor. Chem

Morales-Bayuelo, Matute, Caballero, New Insights from the CoMSIA Analysis within the Framework of Density Functional Theory, J. Mol. Model, doi:10.1007/s00894-015-2690-5

Morales-Bayuelo, New insights in series of ligands used as SARS-CoV-2 virus inhibitors within molecular docking, molecular quantum similarity, and chemical reactivity indices frameworks, Harvard Dataverse, doi:10.7910/DVN/MSIGUS

Morales-Bayuelo, Torres, Baldiris, Theoretical Study of the Chemical Reactivity and Molecular Quantum Similarity in a Series of Derivatives of 2-Adamantyl-thiazolidine-4-one. Using Density Functional Theory and the Topo-Geometrical Superposition Approach, Int. J. Quantum Chem, doi:10.1002/qua.23288

Morales-Bayuelo, Torres, Vivas-Reyes, Hückel treatment of pyrrole and pentalene as a function of cyclopentadienyl using Local Quantum Similarity Index (LQSI) and the Topo-Geometrical Superposition Approach (TGSA), J. Theor. Comput. Chem

Morales-Bayuelo, Valdiris, Vivas-Reyes, Mathematic analysis on a series of 4-Acetylamino-2-(3,5dimethylpyrazol-1-yl)-6-pyridylpyrimidines: a simple way to relate quantum similarity with local chemical reactivity using the Gaussian orbitals localized theory, J. Theor. Chem

Morales-Bayuelo, Vivas-Reyes, Theoretical Calculations and Modeling for the Molecular Polarization of Furan and Thiophene under the Action of an Electric Field Using Quantum Similarity, J. Quantum Chem, doi:10.1155/2014/585394

Morales-Bayuelo, Vivas-Reyes, Theoretical model for the polarization molecular and Hückel treatment of Phospho-Cyclopentadiene in an external electric field: Hirschfeld study, J. Math. Chem, doi:10.1007/s10910-013-0182-3

Morales-Bayuelo, Vivas-Reyes, Topological model on the inductive effect in alkyl halides. Using local quantum similarity and reactivity descriptors in the Density Functional Theory (DFT), J. Quantum Chem, doi:10.1155/2014/850163

Morales-Bayuelo, Vivas-Reyes, Topological model to quantify the global reactivity indexes as local in Diels-Alder reactions, using Density Function Theory (DFT) and Local Quantum Similarity (LQS), J. Math. Chem, doi:10.1007/s10910-012-0069-8

Morales-Bayuelo, Vivas-Reyes, Understanding the Polar Character Trend in a Series of Diels-Alder Reactions Using Molecular Quantum Similarity and Chemical Reactivity Descriptors, J. Quantum Chem, doi:10.1155/2014/239845

Mortier, Yang, The use of global and local molecular parameters for the analysis of the gas-phase basicity of amines, J. Am. Chem. Soc, doi:10.1021/ja00279a008

Parr, Pearson, Absolute hardness: companion parameter to absolute electronegativity, J. Am. Chem. Soc, doi:10.1021/ja00364a005

Parr, Szentpaly, Liu, Electrophilicity Index, J. Am. Chem. Soc, doi:10.1021/ja983494x

Parr, Weitao, Density-Functional Theory of Atoms and Molecules, doi:10.1093/oso/9780195092769.001.0001

Perdew, Wang, Accurate and simple analytic representation of the electron-gas correlation energy, Phys. Rev. B, doi:10.1103/PhysRevB.45.13244

Pye, Ziegler, Van Lenthe, An implementation of the conductor-like screening model of solvation within the Amsterdam density functional package -Part II. COSMO for real solventes, Can. J. Chem, doi:10.1139/V09-008

Qayyum, Mohammad, Slominski, Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 replication machinery enzymes, American Journal of Physiology-Endocrinology and Metabolism, doi:10.1152/ajpendo.00174.2021

Sastry, Adzhigirey, Day, Protein and ligand preparation: parameters, protocols, and influence on virtual screen-ing enrichments, J. Comput. Aided Mol. Des, doi:10.1007/s10822-013-9644-8

Schipper, Gritsenko, Van Gisbergen, Molecular calculations of excitation energies and (hyper) polarizabilities with a statistical average of orbital model exchange-correlation potentials, J. Chem. Phys, doi:10.1063/1.480688

Valdes, Brown, Morales-Bayuelo, Adenosine Derivates as Antioxidant Agents: Synthesis, Characterization, in vitro Activity, and Theoretical Insights, Antioxidants, doi:10.3390/antiox8100468

Van Lenthe, Baerends, Snijders, Relativistic total energy using regular approximations, J. Chem. Phys, doi:10.1063/1.467943

Velde, Bickelhaupt, Baerends, Interaction of Atoms with Grain Surfaces in Steel: Periodic Dependence of Binding Energy on Atomic Number and Influence on Wear Resistance, J. Comput. Chem

Vivas-Reyes, Morales-Bayuelo, Gueto, Study of interaction energies between residues of the active site of Hsp90 and geldanamycin analogues using quantum mechanics/molecular mechanics methods [version 2; peer review: 2 approved, Res, doi:10.12688/f1000research.20844.2

Xu, Liu, Weiss, Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design, Nucleic Acids Res, doi:10.1093/nar/gkg916

Yang, Lin, Na, Homointerface covalent organic framework membranes for efficient desalination, J. Chem. Inf. Model, doi:10.1021/acs.jcim.1c00355

Yang, Wu, Ren, Novel SARS-like Betacoronaviruses in Bats, China, Emerg. Infect. Dis

Young, Ong, Kalimuddin, Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore, JAMA, doi:10.1001/jama.2020.3204

Zhao, Truhlar, The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals, Theoretical Chemical Account, doi:10.1007/s00214-007-0310-x

{ 'indexed': { 'date-parts': [[2023, 12, 12]], 'date-time': '2023-12-12T00:47:42Z', 'timestamp': 1702342062283}, 'update-to': [ { 'updated': { 'date-parts': [[2023, 12, 11]], 'date-time': '2023-12-11T00:00:00Z', 'timestamp': 1702252800000}, 'DOI': '10.12688/f1000research.123550.1', 'type': 'new_version', 'label': 'New version'}, { 'updated': { 'date-parts': [[2023, 12, 11]], 'date-time': '2023-12-11T00:00:00Z', 'timestamp': 1702252800000}, 'DOI': '10.12688/f1000research.123550.2', 'type': 'new_version', 'label': 'New version'}], 'reference-count': 49, 'publisher': 'F1000 Research Ltd', 'license': [ { 'start': { 'date-parts': [[2023, 12, 11]], 'date-time': '2023-12-11T00:00:00Z', 'timestamp': 1702252800000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'funder': [{'name': 'UNISINU-2022-2', 'award': ['BS-PD/2022-01']}], 'content-domain': {'domain': ['f1000research.com'], 'crossmark-restriction': False}, 'abstract': '<ns3:p>Background The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus causes ' 'an infectious illness named coronavirus disease 2019 (COVID-19). SARS-CoV is a positive-sense ' 'single-stranded RNA virus from the <ns3:italic>Betacoronavirus</ns3:italic> genus. The ' 'SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has an important role in the viral life cycle ' 'and its active site is a very accessible region, thus a potential therapeutic approach may be ' 'to target this region to study the inhibition of viral replication. Various preexisting drugs ' 'have been proposed for the treatment of COVID-19 and the use of existing antiviral agents may ' 'reduce the time and cost of new drug discoveries, but the efficacy of these drugs is limited. ' 'Therefore, the aim of the present study was to evaluate a number of ligands used as ' 'SARS-CoV-2 virus inhibitors to determine the suitability of them for potential COVID-19 ' 'treatment. Methods In this study, we selected a series of ligands used as SARS-CoV-2 virus ' 'inhibitors such as: abacavir, acyclovir, amprenavir, ascorbic acid vitamin C, azithromycin, ' 'baloxavir, boceprevir, cholecalciferol vitamin D, cidofovir, edoxudine, emtricitabine, ' 'hydroxychloroquine and remdesivir. These ligands were analyzed using molecular docking, ' 'molecular quantum similarity, and chemical reactivity indices defined within a conceptual ' 'density functional theory framework. Results The analysis of molecular quantum similarity ' 'indices on inhibitors showed a high number of differences from a structural point of view. ' 'However, they are quite similar in their electronic density, obtaining the highest values in ' 'the electronic similarity index. Global and local chemical reactivity indices were analyzed. ' 'Conclusions These studies allowed for the identification of the main stabilizing interactions ' 'using the crystal structure of SARS-CoV-2 RdRp. The molecular quantum similarity and chemical ' 'reactivity descriptors provide novel insights into these ligands that can be used in the ' 'design of new COVID-19 treatments.</ns3:p>', 'DOI': '10.12688/f1000research.123550.3', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 12, 11]], 'date-time': '2023-12-11T16:20:50Z', 'timestamp': 1702311650000}, 'page': '914', 'update-policy': 'http://dx.doi.org/10.12688/f1000research.crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'New findings on ligand series used as SARS-CoV-2 virus inhibitors within the frameworks of ' 'molecular docking, molecular quantum similarity and chemical reactivity indices', 'prefix': '10.12688', 'volume': '11', 'author': [ { 'ORCID': 'http://orcid.org/0000-0001-9159-5289', 'authenticated-orcid': False, 'given': 'Alejandro', 'family': 'Morales-Bayuelo', 'sequence': 'first', 'affiliation': []}, {'given': 'Jesús', 'family': 'Sánchez-Márquez', 'sequence': 'additional', 'affiliation': []}], 'member': '2560', 'published-online': {'date-parts': [[2023, 12, 11]]}, 'reference': [ { 'key': 'ref1', 'doi-asserted-by': 'crossref', 'first-page': '989', 'DOI': '10.3201/eid1906.121648', 'article-title': 'Novel SARS-like Betacoronaviruses in Bats, China, 2011.', 'volume': '19', 'author': 'L Yang', 'year': '2013', 'journal-title': 'Emerg. Infect. Dis.'}, { 'key': 'ref2', 'doi-asserted-by': 'publisher', 'first-page': '7117-7130', 'DOI': '10.1093/nar/gkg916', 'article-title': 'Molecular model of SARS coronavirus polymerase: implications for ' 'biochemical functions and drug design.', 'volume': '31', 'author': 'X Xu', 'year': '2003', 'journal-title': 'Nucleic Acids Res.'}, { 'key': 'ref3', 'first-page': '1384-1386', 'article-title': 'Remdesivir in patients with acute or chronic kidney disease and ' 'COVID-19.', 'volume': '31', 'author': 'M Adamsick', 'year': '2020', 'journal-title': 'J. Am. Soc.'}, { 'key': 'ref4', 'doi-asserted-by': 'publisher', 'first-page': '289-295', 'DOI': '10.1021/ar010048x', 'article-title': 'Molecular Quantum Similarity and the Fundamentals of QSAR.', 'volume': '35', 'author': 'B Emili', 'year': '2002', 'journal-title': 'Acc. Chem. Res.'}, { 'key': 'ref5', 'doi-asserted-by': 'publisher', 'author': 'R Parr', 'year': '1995; 12 Nov. 2020', 'journal-title': 'Density-Functional Theory of Atoms and Molecules.', 'DOI': '10.1093/oso/9780195092769.001.0001'}, { 'key': 'ref6', 'doi-asserted-by': 'publisher', 'first-page': 'D464-D474', 'DOI': '10.1093/nar/gky1004', 'article-title': 'RCSB Protein Data Bank: Biological macromolecular structures enabling ' 'research and education in fundamental biology, biomedicine, ' 'biotechnology and energy.', 'volume': '47', 'author': 'S Burley', 'year': '2019', 'journal-title': 'Nucleic Acids Res.'}, { 'key': 'ref7', 'doi-asserted-by': 'publisher', 'first-page': '1739-1749', 'DOI': '10.1021/jm0306430', 'article-title': 'Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. ' 'Method and Assessment of Docking Accuracy.', 'volume': '47', 'author': 'J Halgren', 'year': '2004', 'journal-title': 'J. Med. Chem.'}, { 'key': 'ref8', 'doi-asserted-by': 'publisher', 'first-page': '1739-1749', 'DOI': '10.1021/jm0306430', 'article-title': 'Glide: A New Approach for Rapid, Accurate Docking and Scor- ing. 1. ' 'Method and Assessment of Docking Accuracy.', 'volume': '47', 'author': 'R Friesner', 'year': '2004', 'journal-title': 'J. Med. Chem.'}, { 'key': 'ref9', 'doi-asserted-by': 'publisher', 'first-page': '221-234', 'DOI': '10.1007/s10822-013-9644-8', 'article-title': 'Protein and ligand preparation: parameters, protocols, and influence on ' 'virtual screen- ing enrichments.', 'volume': '27', 'author': 'G Madhavi Sastry', 'year': '2013', 'journal-title': 'J. Comput. Aided Mol. Des.'}, { 'key': 'ref10', 'doi-asserted-by': 'publisher', 'first-page': '11225-11236', 'DOI': '10.1021/ja9621760', 'article-title': 'Development and Testing of the OPLS All-Atom Force Field on ' 'Conformational Energetics and Properties of Organic Liquids.', 'volume': '118', 'author': 'W Jorgensen', 'year': '1996', 'journal-title': 'J. Am. Chem. Soc.'}, { 'key': 'ref12', 'doi-asserted-by': 'publisher', 'first-page': '156', 'DOI': '10.1007/s00894-015-2690-5', 'article-title': 'New Insights from the CoMSIA Analysis within the Framework of Density ' 'Functional Theory.', 'volume': '21', 'author': 'A Morales-Bayuelo', 'year': '2015', 'journal-title': 'J. Mol. Model.'}, { 'key': 'ref13', 'first-page': '931', 'article-title': 'Interaction of Atoms with Grain Surfaces in Steel: Periodic Dependence ' 'of Binding Energy on Atomic Number and Influence on Wear Resistance.', 'volume': '22', 'author': 'G Te Velde', 'year': '2001', 'journal-title': 'J. Comput. Chem.'}, { 'key': 'ref14', 'doi-asserted-by': 'publisher', 'first-page': '9783-9792', 'DOI': '10.1063/1.467943', 'article-title': 'Relativistic total energy using regular approximations.', 'volume': '101', 'author': 'E Lenthe', 'year': '1994', 'journal-title': 'J. Chem. Phys.'}, { 'key': 'ref15', 'doi-asserted-by': 'publisher', 'first-page': '13244-13249', 'DOI': '10.1103/PhysRevB.45.13244', 'article-title': 'Accurate and simple analytic representation of the electron-gas ' 'correlation energy.', 'volume': '45', 'author': 'J Perdew', 'year': '1992', 'journal-title': 'Phys. Rev. B.'}, { 'key': 'ref16', 'doi-asserted-by': 'publisher', 'first-page': '790-797', 'DOI': '10.1139/V09-008', 'article-title': 'An implementation of the conductor-like screening model of solvation ' 'within the Amsterdam density functional package — Part II. COSMO for ' 'real solventes.', 'volume': '87', 'author': 'C Pye', 'year': '2009', 'journal-title': 'Can. J. Chem.'}, { 'key': 'ref17', 'doi-asserted-by': 'publisher', 'first-page': '1344-1352', 'DOI': '10.1063/1.480688', 'article-title': 'Molecular calculations of excitation energies and (hyper) ' 'polarizabilities with a statistical average of orbital model ' 'exchange-correlation potentials.', 'volume': '112', 'author': 'P Schipper', 'year': '2000', 'journal-title': 'J. Chem. Phys.'}, { 'key': 'ref18', 'doi-asserted-by': 'publisher', 'first-page': '1185-1189', 'DOI': '10.1002/qua.560170612', 'article-title': 'How Similar is a Molecule to Another? An Electron Density Measure of ' 'Similarity Between Two Molecular Structures.', 'volume': '17', 'author': 'R Carbó-Dorca', 'year': '1980', 'journal-title': 'Int. J. Quantum Chem.'}, { 'key': 'ref19', 'doi-asserted-by': 'publisher', 'first-page': '8-20', 'DOI': '10.1002/qua.20191', 'article-title': 'Foundation of quantum similarity measures and their relationship to ' 'QSPR: density function structure, approximations, and application ' 'examples.', 'volume': '101', 'author': 'R Carbó-Dorca', 'year': '2005', 'journal-title': 'Int. J. Quantum Chem.'}, { 'key': 'ref20', 'doi-asserted-by': 'publisher', 'first-page': '127', 'DOI': '10.1002/0471720895.ch2', 'article-title': 'Molecular quantum similarity using conceptual DFT descriptors.', 'volume': '21', 'author': 'P Bultinck', 'year': '2005', 'journal-title': 'Rev. Comput. Chem.'}, { 'key': 'ref21', 'doi-asserted-by': 'publisher', 'first-page': '826-846', 'DOI': '10.1002/(SICI)1096-987X(19970430)18:6<826::AID-JCC8>3.0.CO;2-U', 'article-title': 'Tagged sets, convex sets and quantum similarity measures.', 'volume': '18', 'author': 'P Constans', 'year': '1997', 'journal-title': 'J. Comput. Chem.'}, { 'key': 'ref22', 'doi-asserted-by': 'publisher', 'first-page': '2023-2039', 'DOI': '10.1002/(SICI)1096-987X(199712)18:16<2023::AID-JCC7>3.0.CO;2-N', 'article-title': 'Quantum similarity measures under atomic shell approximation: First ' 'order density fitting using elementary Jacobi rotations.', 'volume': '18', 'author': 'L Amat', 'journal-title': 'J. Comput. Chem.'}, { 'key': 'ref23', 'first-page': '1046-1053', 'article-title': 'Atomic shell approximation: electron density fitting algorithm ' 'restricting coefficients to positive values.', 'volume': '35', 'author': 'P Constans', 'journal-title': 'J. Chem. Inf. Comput. Sci.'}, { 'key': 'ref24', 'doi-asserted-by': 'publisher', 'first-page': '181-228', 'DOI': '10.1016/S0166-1280(00)00363-8', 'article-title': 'Quantum mechanical origin of QSAR: theory and applications.', 'volume': '504', 'author': 'R Carbó-Dorca', 'journal-title': 'J. Mol. Struct. THEOCHEM.'}, { 'key': 'ref25', 'doi-asserted-by': 'publisher', 'first-page': '468', 'DOI': '10.3390/antiox8100468', 'article-title': 'Adenosine Derivates as Antioxidant Agents: Synthesis, Characterization, ' 'in vitro Activity, and Theoretical Insights.', 'volume': '8', 'author': 'F Valdes', 'year': '2019', 'journal-title': 'Antioxidants (Basel).'}, { 'key': 'ref26', 'doi-asserted-by': 'publisher', 'DOI': '10.12688/f1000research.20844.2', 'article-title': 'Study of interaction energies between residues of the active site of ' 'Hsp90 and geldanamycin analogues using quantum mechanics/molecular ' 'mechanics methods [version 2; peer review: 2 approved].', 'volume': '8', 'author': 'R Vivas-Reyes', 'year': '2020', 'journal-title': 'F1000Res.'}, { 'key': 'ref27', 'doi-asserted-by': 'publisher', 'first-page': '2681-2687', 'DOI': '10.1002/qua.23288', 'article-title': 'Theoretical Study of the Chemical Reactivity and Molecular Quantum ' 'Similarity in a Series of Derivatives of ' '2-Adamantyl-thiazolidine-4-one. Using Density Functional Theory and the ' 'Topo-Geometrical Superposition Approach.', 'volume': '112', 'author': 'A Morales-Bayuelo', 'year': '2012', 'journal-title': 'Int. J. Quantum Chem.'}, { 'key': 'ref28', 'doi-asserted-by': 'crossref', 'first-page': '223-239', 'DOI': '10.1142/S0219633612500150', 'article-title': 'Hückel treatment of pyrrole and pentalene as a function of ' 'cyclopentadienyl using Local Quantum Similarity Index (LQSI) and the ' 'Topo-Geometrical Superposition Approach (TGSA).', 'volume': '11', 'author': 'A Morales-Bayuelo', 'year': '2012', 'journal-title': 'J. Theor. Comput. Chem.'}, { 'key': 'ref29', 'doi-asserted-by': 'publisher', 'first-page': '125-143', 'DOI': '10.1007/s10910-012-0069-8', 'article-title': 'Topological model to quantify the global reactivity indexes as local in ' 'Diels–Alder reactions, using Density Function Theory (DFT) and Local ' 'Quantum Similarity (LQS).', 'volume': '51', 'author': 'A Morales-Bayuelo', 'year': '2013', 'journal-title': 'J. Math. Chem.'}, { 'key': 'ref30', 'doi-asserted-by': 'publisher', 'first-page': '1835-1852', 'DOI': '10.1007/s10910-013-0182-3', 'article-title': 'Theoretical model for the polarization molecular and Hückel treatment ' 'of Phospho-Cyclopentadiene in an external electric field: Hirschfeld ' 'study.', 'volume': '51', 'author': 'A Morales-Bayuelo', 'year': '2013', 'journal-title': 'J. Math. Chem.'}, { 'key': 'ref31', 'first-page': '1-13', 'article-title': 'Scale Alpha and Beta of Quantitative Convergence and Chemical ' 'Reactivity Analysis in Dual Cholinesterase/Monoamine Oxidase Inhibitors ' 'for the Alzheimer Disease Treatment using Density Functional Theory ' '(DFT).', 'volume': '13', 'author': 'A Morales-Bayuelo', 'year': '2013', 'journal-title': 'J. Theor. Chem.'}, { 'key': 'ref32', 'doi-asserted-by': 'publisher', 'first-page': '1-10', 'DOI': '10.1155/2014/585394', 'article-title': 'Theoretical Calculations and Modeling for the Molecular Polarization of ' 'Furan and Thiophene under the Action of an Electric Field Using Quantum ' 'Similarity.', 'volume': '2014', 'author': 'A Morales-Bayuelo', 'year': '2014', 'journal-title': 'J. Quantum Chem.'}, { 'key': 'ref33', 'doi-asserted-by': 'publisher', 'first-page': '1-12', 'DOI': '10.1155/2014/850163', 'article-title': 'Topological model on the inductive effect in alkyl halides. Using local ' 'quantum similarity and reactivity descriptors in the Density Functional ' 'Theory (DFT).', 'volume': '2014', 'author': 'A Morales-Bayuelo', 'year': '2014', 'journal-title': 'J. Quantum Chem.'}, { 'key': 'ref34', 'first-page': '1-13', 'article-title': 'Mathematic analysis on a series of ' '4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines: a ' 'simple way to relate quantum similarity with local chemical reactivity ' 'using the Gaussian orbitals localized theory.', 'volume': '14', 'author': 'A Morales-Bayuelo', 'year': '2014', 'journal-title': 'J. Theor. Chem.'}, { 'key': 'ref35', 'doi-asserted-by': 'publisher', 'first-page': '1-19', 'DOI': '10.1155/2014/239845', 'article-title': 'Understanding the Polar Character Trend in a Series of Diels-Alder ' 'Reactions Using Molecular Quantum Similarity and Chemical Reactivity ' 'Descriptors.', 'volume': '2014', 'author': 'A Morales-Bayuelo', 'year': '2014', 'journal-title': 'J. Quantum Chem.'}, { 'key': 'ref36', 'doi-asserted-by': 'publisher', 'first-page': '7512-7516', 'DOI': '10.1021/ja00364a005', 'article-title': 'Absolute hardness: companion parameter to absolute electronegativity.', 'volume': '105', 'author': 'R Parr', 'year': '1983', 'journal-title': 'J. Am. Chem. Soc.'}, { 'key': 'ref37', 'doi-asserted-by': 'publisher', 'first-page': '1793-1874', 'DOI': '10.1021/cr990029p', 'article-title': 'Conceptual density functional theory.', 'volume': '103', 'author': 'P Geerlings', 'year': '2003', 'journal-title': 'Chem. Rev.'}, { 'key': 'ref38', 'doi-asserted-by': 'publisher', 'first-page': '2065-2091', 'DOI': '10.1021/cr040109f', 'article-title': 'Electrophilicity index.', 'volume': '106', 'author': 'P Chattaraj', 'year': '2006', 'journal-title': 'Chem. Rev.'}, { 'key': 'ref39', 'doi-asserted-by': 'publisher', 'first-page': '1922-1924', 'DOI': '10.1021/ja983494x', 'article-title': 'Electrophilicity Index.', 'volume': '121', 'author': 'R Parr', 'year': '1999', 'journal-title': 'J. Am. Chem. Soc.'}, { 'key': 'ref40', 'first-page': '405', 'article-title': 'A direct evaluation of regional Fukui functions in molecules.', 'volume': '30', 'author': 'M Galván', 'year': '1999', 'journal-title': 'Chem. Phys. Lett.'}, { 'key': 'ref41', 'doi-asserted-by': 'publisher', 'first-page': '5708-5711', 'DOI': '10.1021/ja00279a008', 'article-title': 'The use of global and local molecular parameters for the analysis of ' 'the gas-phase basicity of amines.', 'volume': '108', 'author': 'W Mortier', 'year': '1986', 'journal-title': 'J. Am. Chem. Soc.'}, { 'key': 'ref42', 'doi-asserted-by': 'publisher', 'first-page': '2544-2551', 'DOI': '10.1063/1.1305879', 'article-title': 'On the Condensed Fukui Function.', 'volume': '113', 'author': 'P Fuentealba', 'year': '2000', 'journal-title': 'J. Chem. Phys.'}, { 'key': 'ref43', 'doi-asserted-by': 'publisher', 'first-page': '215-241', 'DOI': '10.1007/s00214-007-0310-x', 'article-title': 'The M06 suite of density functionals for main group thermochemistry, ' 'thermochemical kinetics, non-covalent interactions, excited states, and ' 'transition elements: two new functionals and systematic testing of four ' 'M06-class functionals and 12 other functionals.', 'volume': '120', 'author': 'Y Zhao', 'year': '2008', 'journal-title': 'Theoretical Chemical Account.'}, { 'key': 'ref45', 'doi-asserted-by': 'publisher', 'first-page': '3917-3926', 'DOI': '10.1021/acs.jcim.1c00355', 'article-title': 'Homointerface covalent organic framework membranes for efficient ' 'desalination.', 'volume': '61', 'author': 'J Yang', 'year': '2021, 23', 'journal-title': 'J. Chem. Inf. Model.'}, { 'key': 'ref46', 'doi-asserted-by': 'publisher', 'first-page': 'E246-E251', 'DOI': '10.1152/ajpendo.00174.2021', 'article-title': 'Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 ' 'replication machinery enzymes.', 'volume': '321', 'author': 'S Qayyum', 'year': '2021', 'journal-title': 'American Journal of Physiology-Endocrinology and Metabolism.'}, { 'key': 'ref47', 'doi-asserted-by': 'publisher', 'first-page': '3204-3212', 'DOI': '10.1080/07391102.2020.1761882', 'article-title': 'SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: an in silico ' 'perspective.', 'volume': '39', 'author': 'A Elfiky', 'year': '2021', 'journal-title': 'J. Biomol. Struct. Dyn.'}, { 'key': 'ref48', 'doi-asserted-by': 'publisher', 'first-page': '3922', 'DOI': '10.3390/ijms21113922', 'article-title': 'Investigation of Some Antiviral N-Heterocycles as COVID 19 Drug: ' 'Molecular Docking and DFT Calculations.', 'volume': '21', 'author': 'M Hagar', 'year': '2020', 'journal-title': 'Int. J. Mol. Sci.'}, { 'key': 'ref49', 'doi-asserted-by': 'publisher', 'first-page': '2206-2220', 'DOI': '10.1002/pro.4190', 'article-title': 'Vitamin D and COVID-19: A review on the role of vitamin D in preventing ' 'and reducing the severity of COVID-19 infection.', 'volume': '30', 'author': 'M Abdrabbo', 'year': '2021', 'journal-title': 'Protein Sci.'}, { 'key': 'ref50', 'doi-asserted-by': 'publisher', 'first-page': '1488-1494', 'DOI': '10.1001/jama.2020.3204', 'article-title': 'Epidemiologic Features and Clinical Course of Patients Infected With ' 'SARS-CoV-2 in Singapore.', 'volume': '323', 'author': 'B Young', 'year': '2020', 'journal-title': 'JAMA.'}, { 'key': 'ref51', 'doi-asserted-by': 'publisher', 'article-title': 'New insights in series of ligands used as SARS-CoV-2 virus inhibitors ' 'within molecular docking, molecular quantum similarity, and chemical ' 'reactivity indices frameworks. [Dataset].', 'author': 'A Morales-Bayuelo', 'year': '2022', 'DOI': '10.7910/DVN/MSIGUS'}], 'container-title': 'F1000Research', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://f1000research.com/articles/11-914/v3/xml', 'content-type': 'application/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://f1000research.com/articles/11-914/v3/pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://f1000research.com/articles/11-914/v3/iparadigms', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 12, 11]], 'date-time': '2023-12-11T16:21:05Z', 'timestamp': 1702311665000}, 'score': 1, 'resource': {'primary': {'URL': 'https://f1000research.com/articles/11-914/v3'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 12, 11]]}, 'references-count': 49, 'URL': 'http://dx.doi.org/10.12688/f1000research.123550.3', 'relation': {}, 'ISSN': ['2046-1402'], 'subject': [ 'General Pharmacology, Toxicology and Pharmaceutics', 'General Immunology and Microbiology', 'General Biochemistry, Genetics and Molecular Biology', 'General Medicine'], 'container-title-short': 'F1000Res', 'published': {'date-parts': [[2023, 12, 11]]}, 'assertion': [ { 'value': 'Approved', 'URL': 'https://f1000research.com/articles/11-914/v3#article-reports', 'order': 0, 'name': 'referee-status', 'label': 'Referee status', 'group': {'name': 'current-referee-status', 'label': 'Current Referee Status'}}, { 'value': '10.5256/f1000research.153172.r195605, Truong Tan Trung, Dong Nai Technology ' 'University, Vietnam, 22 Aug 2023, version 2, 1 approved', 'URL': 'https://f1000research.com/articles/11-914/v2#referee-response-195605', 'order': 0, 'name': 'referee-response-195605', 'label': 'Referee Report', 'group': {'name': 'article-reports', 'label': 'Article Reports'}}, { 'value': 'This work was supported by UNISINU-2022-I (BS-PD/2022-01; assigned to AMB). The ' 'funders had no role in study design, data collection and analysis, decision to ' 'publish, or preparation of the manuscript.', 'order': 1, 'name': 'grant-information', 'label': 'Grant Information'}, { 'value': 'This is an open access article distributed under the terms of the Creative ' 'Commons Attribution Licence, which permits unrestricted use, distribution, and ' 'reproduction in any medium, provided the original work is properly cited.', 'order': 0, 'name': 'copyright-info', 'label': 'Copyright'}]}

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