Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Anti-Infective Agents
  4. Fast Track Articles
  5. Fast Track Article
image of Sesquiterpene Coumarins as Promising Antiviral Agents: An In-silico Study

Abstract

Background

Sesquiterpene coumarins are a unique class of natural compounds with a wide range of biological activities. These C15 terpenes are connected by ether or carbon-carbon bonds to coumarin derivatives. Sesquiterpene coumarins that include a 7-hydroxylcoumarin (umbelliferone) moiety have significant antiviral properties. The natural flexibility of these compounds reduces the likelihood of developing resistance, which is often seen in viruses due to high mutation rates.

Objective

The lessons learned from the coronavirus pandemic experience emphasize the importance of preparedness for future viral outbreaks in the medical community. Consequently, fast and reliable assessment methods, such as techniques, are crucial in drug discovery.

Methods

In this study, we used studies to evaluate the potential antiviral effects of various sesquiterpene coumarins.

Results

The binding free energy to the spike protein of SARS-CoV-2 suggested that 5′-hydroxyumbelliprenin (), conferol (), 8′-acetoxy-5′-hydroxyumbelliprenin (), and Sanandajine () could be promising antiviral candidates.

Conclusion

These compounds have unique physicochemical characteristics and occupy distinct chemical spaces compared to synthetic libraries; therefore, the criteria for drug-likeness need to be adjusted for this series of compounds.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/aia/10.2174/0122113525360098241219094701
2025-01-29
2025-04-10

  • From This Site

    /content/journals/aia/10.2174/0122113525360098241219094701
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Zumla A. Chan J.F.W. Azhar E.I. Hui D.S.C. Yuen K.Y. Coronaviruses — drug discovery and therapeutic options. Nat. Rev. Drug Discov. 2016 15 5 327 347 10.1038/nrd.2015.37 26868298
    [Google Scholar]
  2. Zaki A.M. Boheemen V.S. Bestebroer T.M. Osterhaus A.D.M.E. Fouchier R.A.M. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 2012 367 19 1814 1820 10.1056/NEJMoa1211721 23075143
    [Google Scholar]
  3. Zhu N Zhang D Wang W Li X Yang B Song J Zhao X Huang B Shi W Lu R A novel coronavirus from patients with Pneumonia in China, 2019. N Engl J Med 2020 382 8 727 733 10.1056/NEJMoa2001017
    [Google Scholar]
  4. World Health Organization Coronavirus disease 2019 (COVID-19): Situation report, 73. Available from: https://iris.who.int/handle/10665/331686 2020 13
  5. Peiris J.S.M. Lai S.T. Poon L.L.M. Guan Y. Yam L.Y.C. Lim W. Nicholls J. Yee W.K.S. Yan W.W. Cheung M.T. Cheng V.C.C. Chan K.H. Tsang D.N.C. Yung R.W.H. Ng T.K. Yuen K.Y. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 2003 361 9366 1319 1325 10.1016/S0140‑6736(03)13077‑2 12711465
    [Google Scholar]
  6. Groot D.R.J. Baker S.C. Baric R.S. Brown C.S. Drosten C. Enjuanes L. Fouchier R.A.M. Galiano M. Gorbalenya A.E. Memish Z.A. Perlman S. Poon L.L.M. Snijder E.J. Stephens G.M. Woo P.C.Y. Zaki A.M. Zambon M. Ziebuhr J. Middle East respiratory syndrome coronavirus (MERS-CoV): Announcement of the coronavirus study group. J. Virol. 2013 87 14 7790 7792 10.1128/JVI.01244‑13 23678167
    [Google Scholar]
  7. Chen Y. Li L. SARS-CoV-2: Virus dynamics and host response. Lancet Infect. Dis. 2020 20 5 515 516 10.1016/S1473‑3099(20)30235‑8 32213336
    [Google Scholar]
  8. Wu G. Yan S. Reasoning of spike glycoproteins being more vulnerable to mutations among 158 coronavirus proteins from different species. J. Mol. Model. 2005 11 1 8 16 10.1007/s00894‑004‑0210‑0 15592899
    [Google Scholar]
  9. Xia S. Zhu Y. Liu M. Lan Q. Xu W. Wu Y. Ying T. Liu S. Shi Z. Jiang S. Lu L. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell. Mol. Immunol. 2020 17 7 765 767 10.1038/s41423‑020‑0374‑2 32047258
    [Google Scholar]
  10. Oany A. Pervin T. Emran A. Design of an epitope-based peptide vaccine against spike protein of human coronavirus: An in silico approach. Drug Des. Devel. Ther. 2014 8 1139 1149 10.2147/DDDT.S67861 25187696
    [Google Scholar]
  11. Sheikhpour M. The current recommended drugs and strategies for the treatment of coronavirus disease (COVID-19). Ther. Clin. Risk Manag. 2020 16 933 946 10.2147/TCRM.S262936 33116543
    [Google Scholar]
  12. Mótyán J.A. Mahdi M. Hoffka G. Tőzsér J. Potential resistance of SARS-CoV-2 main protease (Mpro) against protease inhibitors: Lessons learned from HIV-1 protease. Int. J. Mol. Sci. 2022 23 7 3507 10.3390/ijms23073507 35408866
    [Google Scholar]
  13. Sungkanuparph S. Sukasem C. Manosuthi W. Wiboonchutikul S. Piyavong B. Chantratita W. Tipranavir resistance associated mutations in protease inhibitor-naïve patients with HIV-1 subtype A/E infection. J. Clin. Virol. 2008 43 3 284 286 10.1016/j.jcv.2008.07.002 18701346
    [Google Scholar]
  14. Brogi S. Ramalho T.C. Kuca K. Franco M.J.L. Valko M. In silico methods for drug design and discovery. Front Chem. 2020 8 612 10.3389/fchem.2020.00612 32850641
    [Google Scholar]
  15. Cai Y Zhang J Xiao T Peng H Sterling S M Walsh R M Jr Rawson S Volloch R.S Chen B Distinct conformational states of SARS-CoV-2 spike protein. Science 2020 369 6511 1586 1592
    [Google Scholar]
  16. Bojadzic D. Alcazar O. Chen J. Chuang S.T. Capcha C.J.M. Shehadeh L.A. Buchwald P. Small-molecule inhibitors of the coronavirus spike: ACE2 protein–protein interaction as blockers of viral attachment and entry for SARS-CoV-2. ACS Infect. Dis. 2021 7 6 1519 1534 10.1021/acsinfecdis.1c00070 33979123
    [Google Scholar]
  17. Matheson NJ Lehner PJ How does SARS-CoV-2 cause COVID-19?. Science 2020 369 6503 510 511
    [Google Scholar]
  18. Butler M.S. The role of natural product chemistry in drug discovery. J. Nat. Prod. 2004 67 12 2141 2153 10.1021/np040106y 15620274
    [Google Scholar]
  19. Elfiky A.A. Natural products may interfere with SARS-CoV-2 attachment to the host cell. J. Biomol. Struct. Dyn. 2021 39 9 3194 3203 32340551
    [Google Scholar]
  20. Kao R.Y. Tsui W.H.W. Lee T.S.W. Tanner J.A. Watt R.M. Huang J.D. Hu L. Chen G. Chen Z. Zhang L. He T. Chan K.H. Tse H. To A.P.C. Ng L.W.Y. Wong B.C.W. Tsoi H.W. Yang D. Ho D.D. Yuen K.Y. Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics. Chem. Biol. 2004 11 9 1293 1299 10.1016/j.chembiol.2004.07.013 15380189
    [Google Scholar]
  21. Maldonado G.P. Alvarenga N. Edwards B.A. Giubi F.M.E. Barúa J.E. Rodríguez R.M.C. Rifo S.R. Echeverría V.F. Langjahr P. González C.G. Sotelo P.H. Screening of natural products inhibitors of SARS-CoV-2 entry. Molecules 2022 27 5 1743 10.3390/molecules27051743 35268843
    [Google Scholar]
  22. Cheke R.S. Narkhede R.R. Shinde S.D. Ambhore J.P. Jain P.G. Natural product emerging as potential SARS spike glycoproteins-ACE2 inhibitors to combat COVID-19 attributed by in-silico investigations. Biointerface Res. Appl. Chem. 2021 11 10628 10639
    [Google Scholar]
  23. Oany A.R. Mia M. Pervin T. Junaid M. Hosen S.M.Z. Moni M.A. Design of novel viral attachment inhibitors of the spike glycoprotein (S) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) through virtual screening and dynamics. Int. J. Antimicrob. Agents 2020 56 6 106177 10.1016/j.ijantimicag.2020.106177 32987103
    [Google Scholar]
  24. Yang J. Petitjean S.J.L. Koehler M. Zhang Q. Dumitru A.C. Chen W. Derclaye S. Vincent S.P. Soumillion P. Alsteens D. Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Nat. Commun. 2020 11 1 4541 10.1038/s41467‑020‑18319‑6 32917884
    [Google Scholar]
  25. Gliszczyńska A. Brodelius P.E. Sesquiterpene coumarins. Phytochem. Rev. 2012 11 1 77 96 10.1007/s11101‑011‑9220‑6
    [Google Scholar]
  26. Neese F. Wennmohs F. Becker U. Riplinger C. The ORCA quantum chemistry program package. J. Chem. Phys. 2020 152 22 224108 10.1063/5.0004608 32534543
    [Google Scholar]
  27. O’Boyle N.M. Banck M. James C.A. Morley C. Vandermeersch T. Hutchison G.R. Open Babel: An open chemical toolbox. J. Cheminform. 2011 3 1 33 10.1186/1758‑2946‑3‑33 21982300
    [Google Scholar]
  28. Morris G.M. Huey R. Lindstrom W. Sanner M.F. Belew R.K. Goodsell D.S. Olson A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 2009 30 16 2785 2791 10.1002/jcc.21256 19399780
    [Google Scholar]
  29. Wang Q. Zhang Y. Wu L. Niu S. Song C. Zhang Z. Lu G. Qiao C. Hu Y. Yuen K.Y. Wang Q. Zhou H. Yan J. Qi J. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 2020 181 4 894 904.e9 10.1016/j.cell.2020.03.045 32275855
    [Google Scholar]
  30. Asl R.N. Karimi A. Ebadi A. The potential of natural product vs neurodegenerative disorders: In silico study of artoflavanocoumarin as BACE-1 inhibitor. Comput. Biol. Chem. 2018 77 307 317 10.1016/j.compbiolchem.2018.10.015 30445338
    [Google Scholar]
  31. Asl R.N. Sepehri S. Ebadi A. Miri R. Shahabipour S. Molecular docking and quantum mechanical studies on biflavonoid structures as BACE-1 inhibitors. Struct. Chem. 2015 26 2 607 621 10.1007/s11224‑014‑0523‑2
    [Google Scholar]
  32. Jakalian A. Bush B.L. Jack D.B. Bayly C.I. Fast, efficient generation of high-quality atomic charges. AM1-BCC model: I. Method. J. Comput. Chem. 2000 21 2 132 146 10.1002/(SICI)1096‑987X(20000130)21:2<132::AID‑JCC5>3.0.CO;2‑P
    [Google Scholar]
  33. Essmann U. Perera L. Berkowitz M.L. Darden T. Lee H. Pedersen L.G. A smooth particle mesh Ewald method. J. Chem. Phys. 1995 103 19 8577 8593 10.1063/1.470117
    [Google Scholar]
  34. Berendsen HJC Postma JPM van Gunsteren V.WF Molecular dynamics with coupling to an external bath. J. Chem. Phys. 1984 81 8 3684 3690
    [Google Scholar]
  35. Parrinello M. Rahman A. Polymorphic transitions in single crystals: A new molecular dynamics method. J. Appl. Phys. 1981 52 12 7182 7190 10.1063/1.328693
    [Google Scholar]
  36. Bemis G.W. Murcko M.A. The properties of known drugs. 1. Molecular frameworks. J. Med. Chem. 1996 39 15 2887 2893 10.1021/jm9602928 8709122
    [Google Scholar]
  37. Lovering F. Bikker J. Humblet C. Escape from flatland: Increasing saturation as an approach to improving clinical success. J. Med. Chem. 2009 52 21 6752 6756 10.1021/jm901241e 19827778
    [Google Scholar]
  38. Daina A. Michielin O. Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 2017 7 1 42717 10.1038/srep42717 28256516
    [Google Scholar]
  39. Veber D.F. Johnson S.R. Cheng H.Y. Smith B.R. Ward K.W. Kopple K.D. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 2002 45 12 2615 2623 10.1021/jm020017n 12036371
    [Google Scholar]
  40. Kortemme T. Kim D.E. Baker D. Computational alanine scanning of protein-protein interfaces. Sci. STKE 2004 2004 219 pl2 pl2 10.1126/stke.2192004pl2 14872095
    [Google Scholar]
  41. Williamson G. Kerimi A. Testing of natural products in clinical trials targeting the SARS-CoV-2 (Covid-19) viral spike protein-angiotensin converting enzyme-2 (ACE2) interaction. Biochem. Pharmacol. 2020 178 114123 10.1016/j.bcp.2020.114123 32593613
    [Google Scholar]
  42. Wu C. Liu Y. Yang Y. Zhang P. Zhong W. Wang Y. Wang Q. Xu Y. Li M. Li X. Zheng M. Chen L. Li H. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm. Sin. B 2020 10 5 766 788 10.1016/j.apsb.2020.02.008 32292689
    [Google Scholar]
  43. Smith M Smith J C Repurposing therapeutics for COVID-19: Supercomputer-based docking to the SARS-CoV-2 viral spike protein and viral spike protein-human ACE2 interface. ChemRxiv 2020 10.26434/chemrxiv.11871402.v4
    [Google Scholar]
  44. Senathilake K Samarakoon S Tennekoon K Virtual screening of inhibitors against spike glycoprotein of 2019 novel corona virus: A drug repurposing approach. Preprints 2020 2020030042 10.20944/preprints202003.0042.v1
    [Google Scholar]
  45. Moorthy V. Restrepo H.A.M. Preziosi M.P. Swaminathan S. Data sharing for novel coronavirus (COVID-19). Bull. World Health Organ. 2020 98 3 150 10.2471/BLT.20.251561 32132744
    [Google Scholar]
  46. Calligari P. Bobone S. Ricci G. Bocedi A. Molecular investigation of SARS–CoV-2 proteins and their interactions with antiviral drugs. Viruses 2020 12 4 445 10.3390/v12040445 32295237
    [Google Scholar]
  47. Cao B. Wang Y. Wen D. Liu W. Wang J. Fan G. Ruan L. Song B. Cai Y. Wei M. Li X. Xia J. Chen N. Xiang J. Yu T. Bai T. Xie X. Zhang L. Li C. Yuan Y. Chen H. Li H. Huang H. Tu S. Gong F. Liu Y. Wei Y. Dong C. Zhou F. Gu X. Xu J. Liu Z. Zhang Y. Li H. Shang L. Wang K. Li K. Zhou X. Dong X. Qu Z. Lu S. Hu X. Ruan S. Luo S. Wu J. Peng L. Cheng F. Pan L. Zou J. Jia C. Wang J. Liu X. Wang S. Wu X. Ge Q. He J. Zhan H. Qiu F. Guo L. Huang C. Jaki T. Hayden F.G. Horby P.W. Zhang D. Wang C. A trial of lopinavir–ritonavir in adults hospitalized with severe COVID-19. N. Engl. J. Med. 2020 382 19 1787 1799 10.1056/NEJMoa2001282 32187464
    [Google Scholar]
  48. Trezza A. Iovinelli D. Santucci A. Prischi F. Spiga O. An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors. Sci. Rep. 2020 10 1 13866 10.1038/s41598‑020‑70863‑9 32807895
    [Google Scholar]
  49. Hilgenfeld R. From SARS to MERS : Crystallographic studies on coronaviral proteases enable antiviral drug design. FEBS J. 2014 281 18 4085 4096 10.1111/febs.12936 25039866
    [Google Scholar]
  50. Blackadar C.B. Historical review of the causes of cancer. World J. Clin. Oncol. 2016 7 1 54 86 10.5306/wjco.v7.i1.54 26862491
    [Google Scholar]
/content/journals/aia/10.2174/0122113525360098241219094701
Loading
Sesquiterpene Coumarins as Promising Antiviral Agents: An In-silico Study
Bentham Science Publishers ; https://doi.org/10.2174/0122113525360098241219094701
/content/journals/aia/10.2174/0122113525360098241219094701
/content/journals/aia/10.2174/0122113525360098241219094701
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: spike protein ; molecular docking ; molecular dynamics simulation ; Antivirus ; sesquiterpene coumarins ; COVID-19

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test