Investigation of Nirmatrelvir with Different Crystal Structures Effective on SARS-CoV-2 by In Silico Approaches

Yıl 2022, Cilt: 12 Sayı: 3, 1615 - 1623, 01.09.2022

Burçin Türkmenoğlu

https://doi.org/10.21597/jist.1132663

Öz

A pandemic has been declared in the world with the Covid-19 disease caused by the
SARS-CoV-2 virus. Scientists on this disease, which is of antiviral origin, have been seeking treatment
against SARS-CoV-2 with experimental and computational methods since December 2019.
Nirmatrelvir (PF-07321332; NMV), the antiviral component of PAXLOVID™, has been introduced as
an inhibitor of the main protease (MPro) of this disease, which is a threat to human health, SARS-CoV-
2. By analyzing the binding interactions between the target and the ligand as in silico with the
molecular docking method of Computer Aided Drug Design (CADD), parameters such as amino acids
in the binding site, docking score values, binding energy values can be determined. In this study, to six
different binding parameters (Docking score, XP GScore, Glide evdw, Glide energy, Glide emodel,
MM-GBSA ΔGBind) of Nirmatelvir, an orally taken drug, on the effective crystal structures (7O46,
7QBB, 7NEO, 7B77, 7B2U, 7B2J, 7NBT and 7TVX) of MPro in SARS-CoV-2, were investigated with
Schrödinger 2021-2 (Schrödinger, LLC New York, ABD) software. It is presented in this study that
different crystal structures have different interactions.

Anahtar Kelimeler

SARS-Cov-2, MPro, Nirmatrelvir, molecular docking

Teşekkür

Author would like to thank Erzincan Binali Yıldırım University, Basic Sciences Application and Research Center (EBYU-EUTAM) for the Schrödinger Maestro 2021-2 program.

Kaynakça

• Allam AE, Abouelela ME, Assaf HK, Sayed AM, Nafady AM, El-Shanawany MA, Ohta T, 2021. Phytochemical and in silico studies for potential constituents from Centaurium spicatum as candidates against the SARS-CoV-2 main protease and RNA-dependent RNA polymerase. Natural Product Research, 1-8.
• Anil DA, Aydin BO, Demir Y, Turkmenoglu B, 2022. Design, synthesis, biological evaluation and molecular docking studies of novel 1H-1, 2, 3-Triazole derivatives as potent inhibitors of carbonic anhydrase, acetylcholinesterase and aldose reductase. Journal of Molecular Structure, 1257, 132613.
• Asrani P, Hasan GM, Sohal SS, Hassan MI, 2020. Molecular Basis of Pathogenesis of Coronaviruses: A Comparative Genomics Approach to Planetary Health to Prevent Zoonotic Outbreaks in the 21st Century. Omics-a Journal of Integrative Biology, 24(11), 634-644. doi:10.1089/omi.2020.013.
• Asrani P, Tiwari K, Eapen MS, McAlinden KD, Haug G, Johansen MD, Sohal SS, 2022. Clinical features and mechanistic insights into drug repurposing for combating COVID-19. International Journal of Biochemistry & Cell Biology, 142. doi:ARTN 10611410.1016/j.biocel.2021.106114.
• Boozari M, Hosseinzadeh H, 2021. Natural products forCOVID-19 prevention and treatment regarding to previous coronavirus infections and novel studies. Phytotherapy Research, 35(2), 864-876. doi:10.1002/ptr.6873.
• Catalan IP, Marti CR, de la Sota DP, Alvarez AC, Gimeno MJE, Juana SF, Rincon JMR, 2022. Corticosteroids for COVID-19 symptoms and quality of life at 1 year from admission. Journal of Medical Virology, 94(1), 205-210. doi:10.1002/jmv.27296.
• Çöl ÖF, Bozbey İ, Türkmenoğlu B, Uysal M, 2022. 3 (2H)-Pyridazinone Derivatives: Synthesis, In-Silico Studies, Structure-Activity Relationship and In-Vitro Evaluation for Acetylcholinesterase Enzyme İnhibition. Journal of Molecular Structure, 132970.
• Dadou S, Altay A, Koudad M, Türkmenoğlu B, Yeniçeri E, Çağlar S, Karrouchi K, 2022. Design, synthesis, anticancer evaluation and molecular docking studies of new imidazo [2, 1-b] thiazole-based chalcones. Medicinal Chemistry Research, 1-15.
• Frisch M, Clemente F, 2009. Gaussian 09, Revision A. 01, MJ Frisch, GW Trucks, HB Schlegel, GE Scuseria, MA Robb, JR Cheeseman, G. Scalmani, V. Barone, B. Mennucci, GA Petersson, H. Nakatsuji, M. Caricato, X. Li, HP Hratchian, AF Izmaylov, J. Bloino, G. Zhe.
• Hoffmann M, Krüger N, Schulz S, Cossmann A, Rocha C, Kempf A, Winkler MS, 2022. The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic. Cell, 185(3), 447-456.
• https://www.worldometers.info/coronavirus/.
• Kuzu B, Hepokur C, Turkmenoglu B, Burmaoglu S, Algul O, 2022. Design, synthesis and in vitro antiproliferation activity of some 2-aryl and -heteroaryl benzoxazole derivatives. Future Medicinal Chemistry. doi:10.4155/fmc-2022-0076.
• Laskowski RA, Swindells MB, 2011. LigPlot+: multiple ligand–protein interaction diagrams for drug discovery. In: ACS Publications.
• Li JN, Abel R, Zhu K, Cao YX, Zhao SW, Friesner RA, 2011. The VSGB 2.0 model: A next generation energy model for high resolution protein structure modeling. Proteins-Structure Function and Bioinformatics, 79(10), 2794-2812. doi:10.1002/prot.23106.
• Luttens A, Gullberg H, Abdurakhmanov E, Vo DD, Akaberi D, Talibov VO, Carlsson J, 2022. Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses. Journal of the American Chemical Society, 144(7), 2905-2920. doi:10.1021/jacs.1c08402.
• Owen DR, Allerton CMN, Anderson AS, Aschenbrenner L, Avery M, Berritt S, Zhu YA, 2021. An oral SARS-CoV-2 M-pro inhibitor clinical candidate for the treatment of COVID-19. Science, 374(6575), 1586-+. doi:10.1126/science.abl4784.
• Painter GR, Natchus MG, Cohen O, Holman W, Painter WP, 2021. Developing a direct acting, orally available antiviral agent in a pandemic: the evolution of molnupiravir as a potential treatment for COVID-19. Current Opinion in Virology, 50, 17-22. doi:10.1016/j.coviro.2021.06.003.
• Rai DK, Yurgelonis I, McMonagle P, Rothan HA, Hao L, Gribenko A, Zhu Y, 2022. Nirmatrelvir, an orally active MPro inhibitor, is a potent inhibitor of SARS-CoV-2 Variants of Concern. bioRxiv.
• Schrödinger Release 2021-2: Glide, S., LLC, New York, NY, 2021.
• Schrödinger Release 2021-2: LigPrep, S., LLC, New York, NY, 2021.
• Schrödinger Release 2021-2: Prime, S., LLC, New York, NY, 2021.
• Schrödinger Release 2021-2: Protein Preparation Wizard; Epik, S., LLC, New York, NY, 2021; Impact, Schrödinger, LLC, New York, NY; Prime, Schrödinger, LLC, New York, NY, 2021.
• Ullrich S, Ekanayake KB, Otting G, Nitsche C, 2022. Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir. Bioorganic & Medicinal Chemistry Letters, 128629.