Koray SAYIN, Hilmi ATASEVEN

Structural, Electronic, ADME and p450 Analyses of Boron Containing Compounds against Omicron Variant (B.1.1.529) in SARS-CoV-2

Eight boron compounds are investigated in this study. Structural and spectral characterization is done at M062X/6-311G(d) level in the water. Active sites of these compounds are determined using contour plots of frontier molecular orbital, molecular electrostatic potential (MEP) maps and MEP contour.. Electrophilic and nucleophilic attack regions are determined. We aimed to determine whether boron compounds inhibitor used in the treatment of omicron variant of SARS-CoV-2. Since SARS-CoV-2 is a worldwide health problem, anti-viral properties of studied boron compounds were investigated using in silico techniques. Bioavaliability analyses were performed using ADME and p450. It was found that compound B7 can be good drug candidate against omicron variant of SARS-CoV-2.

Keywords:

Boron-Imine compounds, SARS-CoV-2_Omicron, p450 ADME, Molecular docking.,

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[1] Singhal T., A review of coronavirus disease-2019 (COVID-19), Indian J. Pediatr, 87(4) (2020) 281–286.
[2] Ataseven H., Sayin K., Tüzün B., Gedikli M.A., Could boron compounds be effective against SARS-CoV-2?, Bratislava Medical Journal, 122(10) (2021) 753-758.
[3] Tüzün B., Nasibova T., Garaev E., Sayin K., Ataseven H., Could Peganum harmala be effective in the treatment of COVID-19?, Bratislava Medical Journal, 122(9) (2021) 670-679.
[4] Gokalp F., Sayin K., The highly protective natural medical agents against COVID-19, Bratislava Medical Journal 122(9) (2021) 631-635.
[5] Cetiner E., Sayin K., Tüzün B., Ataseven H., Could boron-containing compounds (BCCs) be effective against SARS-CoV-2 as anti-viral agent?, Bratislava Medical Journal, 122(4) (2021) 263-269.
[6] Aktaş A., Tüzün B., Aslan R., Sayin K., Ataseven H., New anti-viral drugs for the treatment of COVID-19 instead of favipiravir, Journal of Biomolecular Structure and Dynamics, 39(18) (2021) 7263-7273.
[7] Enhancing response to Omicron SARS-CoV-2 variant: Technical brief and priority actions for Member States. World Health Organization: Headquarters, Geneve, Switzerland, Update #6: 21 January 2022, https://www.who.int/publications/m/item/enhancing-readiness-for-omicron-(b.1.1.529)-technical-brief-and-priority-actions-for-member-states.
[8] Pasa S., Aydın S., Kalaycı S., Boğa M., Atlan M., Bingul M., Şahin F., Temel H., The synthesis of boronic-imine structured compounds and identification of their anticancer, antimicrobial and antioxidant activities, Journal of Pharmaceutical Analysis, 6 (2016) 39-48.
[9] Gömeç M., Yulak F., Gezegen H., Özkaraca M., Sayin K., Ataseven H., Synthesis of diaryl urea derivatives and evaluation of their antiproliferative activities in colon adenocarcinoma, Journal of Molecular Structure, 1254 (2022) 132318.
[10] Vanitha U., Elancheran R., Manikandan V., Kabilan S., Krishnasamy K., Design, synthesis, characterization, molecular docking and computational studies of 3-phenyl-2-thioxoimidazolidin-4-one derivatives, Journal of Molecular Structure, 1246 (2021) 131212.
[11] Govindarasu M., Ganeshan S, Ansari M.A., Alomary M.N., Alyahya S., Alghamdi S., Almehmadi M., Rajakumar G., Thiruvengadam M., Vaiyapuri M., In silico modeling and molecular docking insights of kaempferitrin for colon cancer-related molecular targets, Journal of Saudi Chemical Society, 25(9) (2021) 101319.
[12] GaussView, Version 6.1, Roy Dennington, Todd A. Keith, and John M. Millam, Semichem Inc., Shawnee Mission, KS, 2016.
[13] Gaussian 16, Revision B.01, Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb M.A., Cheeseman J.R., Scalmani G., Barone V., Petersson G.A., Nakatsuji H., Li X., Caricato M., Marenich A.V., Bloino J., Janesko B.G., Gomperts R., Mennucci B., Hratchian H.P., Ortiz J.V., Izmaylov A.F., Sonnenberg J.L., Williams-Young D., Ding F., Lipparini F., Egidi F., Goings J., Peng B., Petrone A., Henderson T., Ranasinghe D., Zakrzewski V.G., Gao J., Rega N., Zheng G., Liang W., Hada M., Ehara M., Toyota K., Fukuda R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Vreven T., Throssell K., Montgomery J.A. Jr., Peralta J.E., Ogliaro F., Bearpark M.J., Heyd J.J., Brothers E.N., Kudin K.N., Staroverov V.N., Keith T.A., Kobayashi R., Normand J., Raghavachari K., Rendell A.P., Burant J.C., Iyengar S.S., Tomasi J., Cossi M., Millam J.M., Klene M., Adamo C., Cammi R., Ochterski J.W., Martin R.L., Morokuma K., Farkas O., Foresman J.B., Fox, Gaussian, Inc., Wallingford CT, 2016.
[14] Perkin Elmer, ChemBioDraw Ultra Version (13.0.0.3015), 2012.
[15] Kirchdoerfer R.N., Ward A.B, Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors, Nat. Commun., 10 (2019) 2342.
[16] Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.L., Abiona O., Graham B.S., McLellan J.S., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation, Science, 367 (2020) 1260-1263.
[17] Anson B., Mesecar A., X-ray Structure of SARS-CoV-2 main protease bound to Boceprevir at 1.45 A. https://www.rcsb.org/structure/6WNP.
[18] Ni D., Lau K., Turelli P., Raclot C., Beckert B., Nazarov S., Pojer F., Myasnikov A., Stahlberg H., Trono D., Structural analysis of the Spike of the Omicron SARS-COV-2 variant by cryo-EM and implications for immune evasion, Biorxiv., (2021).
[19] Release S. 3: Maestro, Schrödinger, LLC: New York, NY, USA, 2019.
[20] Schrödinger L. Schrödinger Release 2019-4: LigPrep. New York, NY: Schrödinger, LLC. 2019.
[21] Friesner R.A., Murphy R.B., Repasky M.P., Frye L.L., Greenwood J.R., Halgren T.A., Sanschagrin P.C., Mainz D.T., Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein− ligand complexes, J. Med. Chem., 49(21) (2006) 6177–6196.
[22] Friesner R.A., Banks J.L., Murphy R.B., Halgren T.A., Klicic J.J., Mainz D.T., Repasky M.P., Knoll E.H., Shelley M., Perry J.K., Shaw D.E., Francis P., Shenkin P.S., Glide: a new approach for rapid, accurate docking and scoring. Method and assessment of docking accuracy, J. Med. Chem., 47(7) (2004) 1739–1749.