Structural analyses of vanillin derivative compounds and their molecular docking with mpro and rdrp enzymes of covid-19

Harismah K., Fazeli F., Zandi H.

Department of Chemical Engineering, Faculty of Engineering, Universitas Muhammadiyah Surakarta, Surakarta, Indonesia; Department of Biology, Payame Noor University, Tehran, Iran; Department of Chemistry, Faculty of Science, University of Qom, Qom, Iran


In this work, structural analyses of vanillin (Vanl) and eleven of its derivatives based on the modification of the aldehyde group were investigated using density functional theory (DFT) calculations. In this regard, molecular orbital features and atomic-scale quadrupole coupling constants were evaluated for geometrically optimized structures to see the impact of structural modification on the whole structure. The results indicated that the main impact of such modification was significant only for the modification region, whereas the impact on the rest of the structure was almost negligible. However, electronic features indicated a different tendency for Vanl derivatives for involving in interaction with enzymatic targets. Because of the importance of innovating medication for COVID-19, main protease (MPro) and RNA-dependent RNA polymerase (RdRp) were chosen for the enzymatic target of Vanl ligands for the formation of ligand-target complexes through performing molecular docking (MD) simulations. The results indicated that among the complexes, Vanl 9 (–NHNH2) and 11 (–CH2Cl) could work as the best ligands for interacting with each of RdRp and MPro, respectively. Consequently, optimization of Vanl derivatives could help innovate new compounds for the possible medication of the COVID-19 pandemic. © 2021 by the authors.

COVID-19; DFT; Molecular docking; Structural analysis; Vanillin


Biointerface Research in Applied Chemistry

Publisher: AMG Transcend Association

Volume 12, Issue 2, Art No , Page 1660 – 1669, Page Count

Journal Link:

doi: 10.33263/BRIAC122.16601669

Issn: 20695837



Ozkendir, O.M., Askar, M., Kocer, N.E., Influence of the epidemic COVID-19: an outlook on health, business and scientific studies (2020) Lab-in-Silico, 1, pp. 26-30. ,; MaassenVanDenBrink, A., De Vries, T., Danser, A.J., Headache medication and the COVID-19 pandemic (2020) The Journal of Headache and Pain, 21, pp. 1-4. ,; Alexander, M., Jupp, J., Chazan, G., O’Connor, S., Chan, A., Global oncology pharmacy response to COVID-19 pandemic: medication access and safety (2020) Journal of Oncology Pharmacy Practice, 26, pp. 1225-1229. ,; Harismah, K., Mirzaei, M., Da’I, M., Roshandel, Z., Salarrezaei, E., In silico investigation of nanocarbon biosensors for diagnosis of COVID-19 (2021) Eurasian Chemical Communications, 3, pp. 95-102. ,; Choo, E.K., Rajkumar, S.V., Medication shortages during the COVID-19 crisis: what we must do (2020) Mayo Clinic Proceedings, 95, pp. 1112-1115. ,; Wang, X., Guan, Y., COVID‐19 drug repurposing: a review of computational screening methods, clinical trials, and protein interaction assays (2021) Medicinal Research Reviews, 41, pp. 5-28. ,; Mirzaei, M., Harismah, K., Da’I, M., Salarrezaei, E., Roshandel, Z., Screening efficacy of available HIV protease inhibitors on COVID-19 protease (2020) Journal Military Medicine, 22, pp. 100-107. ,; Zandi, H., Harismah, K., Computer-based tools for structural characterizations and activity specifications of natural products: a quick review (2021) Lab-in-Silico, 2, pp. 50-54. ,; Arya, S.S., Rookes, J.E., Cahill, D.M., Lenka, S.K., Vanillin: a review on the therapeutic prospects of a popular flavouring molecule (2021) Advances in Traditional Medicine, pp. 1-7. ,; Al-Douh, M.H., Selim, E.A., Abdallah, H.H., Abdullah, H.Y., Al-Bakri, A.K., Al-Nohey, D.S., Mahram, S.M., Hawiel, F.A., Molecular docking study of some nitro diazo dye derivatives as antiviral candidates of COVID-19 (2021) Asian Journal of Applied Chemistry Research, pp. 8-15. ,; Law, W.Y., Asaruddin, M.R., Bhawani, S.A., Mohamad, S., Pharmacophore modelling of vanillin derivatives, favipiravir, chloroquine, hydroxychloroquine, monolaurin and tetrodotoxin as MPro inhibitors of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (2020) BMC Research Notes, 13, pp. 1-8. ,; Fu, L., Xie, K., Wu, D., Wang, A., Zhang, H., Ji, Z., Electrochemical determination of vanillin in food samples by using pyrolyzed graphitic carbon nitride (2020) Materials Chemistry and Physics, 242, p. 122462. ,; de Souza Neto, L.R., Moreira-Filho, J.T., Neves, B.J., Maidana, R.L., Guimarães, A.C., Furnham, N., Andrade, C.H., Silva, F.P., In silico strategies to support fragment-to-lead optimization in drug discovery (2020) Frontiers in Chemistry, 8, p. 93. ,; Kandeel, M., Al-Nazawi, M., Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease (2020) Life Sciences, 251, p. 117627. ,; Harismah, K., Mirzaei, M., Favipiravir: structural analysis and activity against COVID-19 (2020) Advanced Journal of Chemistry B, 2, pp. 55-60. ,; Tian, L., Qiang, T., Liang, C., Ren, X., Jia, M., Zhang, J., Li, J., Liu, H., RNA-dependent RNA polymerase (RdRp) inhibitors: the current landscape and repurposing for the COVID-19 pandemic (2021) European Journal of Medicinal Chemistry, 213, p. 113201. ,; Alexpandi, R., De Mesquita, J.F., Pandian, S.K., Ravi, A.V., Quinolines-based SARS-CoV-2 3CLpro and RdRp inhibitors and Spike-RBD-ACE2 inhibitor for drug-repurposing against COVID-19: an in silico analysis (2020) Frontiers in Microbiology, 11, p. 1796. ,; Harismah, K., Mirzaei, M., COVID-19: a serious warning for emergency health innovation (2020) Advanced Journal of Science and Engineering, 1, pp. 32-33. ,; Udwadia, Z.F., Singh, P., Barkate, H., Patil, S., Rangwala, S., Pendse, A., Kadam, J., Tandon, M., Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: a randomized, comparative, open-label, multicenter, phase 3 clinical trial (2021) International Journal of Infectious Diseases, 103, pp. 62-71. ,; Narkhede, R.R., Pise, A.V., Cheke, R.S., Shinde, S.D., Recognition of natural products as potential inhibitors of COVID-19 main protease (Mpro): In-silico evidences (2020) Natural products and Bioprospecting, 10, pp. 297-306. ,; Pence, H.E., Williams, A., ChemSpider: an online chemical information resource (2010) Journal of Chemical Education, 87, pp. 1123-1124. ,; Frisch, M., Trucks, G., Schlegel, H., Scuseria, G., Robb, M., Cheeseman, J., Montgomery, J., Burant, J., (2009) Gaussian 09 D.01 Program, , Gaussian. Inc.: Wallingford, CT, USA; Seif, A., Mirzaei, M., Aghaie, M., Boshra, A., AlN nanotubes: a DFT study of Al-27 and N-14 electric field gradient tensors (2007) Zeitschrift für Naturforschung A, 62, pp. 711-715. ,; Goodsell, D.S., Zardecki, C., Di Costanzo, L., Duarte, J.M., Hudson, B.P., Persikova, I., Segura, J., Burley, S.K., RCSB protein data bank: enabling biomedical research and drug discovery (2020) Protein Science, 29, pp. 52-65. ,; Jin, Z., Du, X., Xu, Y., Deng, Y., Liu, M., Zhao, Y., Zhang, B., Yang, H., Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors (2020) Nature, 582, pp. 289-293. ,; Kirchdoerfer, R.N., Ward, A.B., Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors (2019) Nature Communications, 10, pp. 1-9. ,; Patil, N.S., Rohane, S.H., Organization of swiss dock: in study of computational and molecular docking study (2021) Asian Journal of Research in Chemistry, 14, pp. 145-148. ,; Rad, A.S., Mirabi, A., Peyravi, M., Mirzaei, M., Nickel-decorated B12P12 nanoclusters as a strong adsorbent for SO2 adsorption: quantum chemical calculations (2017) Canadian Journal of Physics, 95, pp. 958-962. ,; Sherafati, M., Rad, A.S., Ardjmand, M., Heydarinasab, A., Peyravi, M., Mirzaei, M., Beryllium oxide (BeO) nanotube provides excellent surface towards adenine adsorption: a dispersion-corrected DFT study in gas and water phases (2018) Current Applied Physics, 18, pp. 1059-1065. ,; Mirzaei, M., Elmi, F., Hadipour, N.L., A systematic investigation of hydrogen-bonding effects on the 17O, 14N, and 2H nuclear quadrupole resonance parameters of anhydrous and monohydrated cytosine crystalline structures: a density functional theory study (2006) The Journal of Physical Chemistry B, 110, pp. 10991-10996. ,; Khalid, H., Hussain, R., Hafeez, A., Virtual screening of piperidine based small molecules against COVID-19 (2020) Lab-in-Silico, 1, pp. 50-55. ,; Idris, M.O., Adeniji, S.E., Habib, K., Adeiza, A.A., Molecular docking of some novel quinoline derivatives as potent inhibitors of human breast cancer cell line (2021) Lab-in-Silico, 2, pp. 30-37. ,; Mirzaei, M., Mirzaei, M., Sulfur doping at the tips of (6, 0) boron nitride nanotube: a DFT study (2010) Physica E, 42, pp. 2147-2150. ,; Mirzaei, M., Hadipour, N.L., Density functional calculations of 14N and 11B NQR parameters in the H-capped (6, 0) and (4, 4) single-walled BN nanotubes (2008) Physica E, 40, pp. 800-804. ,; Mirzaei, M., Yousefi, M., Computational studies of the purine-functionalized graphene sheets (2012) Superlattices and Microstructures, 52, pp. 612-617. ,

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