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Article

In Silico Evaluation of Binding of 2-Deoxy-D-Glucose with Mpro of nCoV to Combat COVID-19

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Department of Chemistry, Atma Ram Sanatan Dharma College, University of Delhi, New Delhi 110021, India
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Department of Chemistry, Sri Ramasami Memorial (SRM) Institute of Science and Technology, Modinagar, Ghaziabad 231206, India
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Department of Zoology, Deen Dayal Upadhyaya College, University of Delhi, New Delhi 110078, India
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Department of Chemistry, Indian Institute of Technology, New Delhi 110016, India
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Department of Biotechnology, The University of Suwon, Hwaseong 18323, Korea
6
Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Korea
*
Authors to whom correspondence should be addressed.
Academic Editor: Marios Spanakis
Pharmaceutics 2022, 14(1), 135; https://doi.org/10.3390/pharmaceutics14010135
Received: 23 November 2021 / Revised: 29 December 2021 / Accepted: 30 December 2021 / Published: 6 January 2022
(This article belongs to the Special Issue In Silico Pharmacology for Evidence-Based and Precision Medicine)
COVID-19 has threatened the existence of humanity andthis infection occurs due to SARS-CoV-2 or novel coronavirus, was first reported in Wuhan, China. Therefore, there is a need to find a promising drug to cure the people suffering from the infection. The second wave of this viral infection was shaking the world in the first half of 2021. Drugs Controllers of India has allowed the emergency use of 2-deoxy-D-glucose (2DG) in 2021 for patients suffering from this viral infection. The potentiality of 2-deoxy-D-glucose to intervene in D-glucose metabolism exists and energy deprivation is an effective parameter to inhibit cancer cell development. Once 2DG arrives in the cells, it becomes phosphorylated to 2-deoxy-D-glucose-6-phosphate (2-DG6P), a charged molecule expressively captured inside the cells. On the other hand, 2DG lacks the ability to convert into fructose-6-phosphate, resulting in a hampering of the activity of both glucose-6-phosphate isomerase and hexokinase, and finally causing cell death. Hence, the potential and effectiveness of 2DG with the main protease (Mpro) of novel coronavirus (nCoV) should be investigated using the molecular docking and molecular dynamics (MD) simulations. The ability of 2DG to inhibit the Mpro of nCoV is compared with 2-deoxyglucose (2DAG), an acyclic molecule, and 2-deoxy-D-ribose (2DR). The binding energy of the molecules with the Mpro of nCoV is calculated using molecular docking and superimposed analysis data is obtained. The binding energy of 2DG, 2DR and 2DAG was −2.40, −2.22 and −2.88 kcal/mol respectively. Although the molecular docking does not provide reliable information, therefore, the binding affinity can be confirmed by molecular dynamics simulations. Various trajectories such as Rg, RMSD, RMSF, and hydrogen bonds are obtained from the molecular dynamics (MD) simulations. 2DG was found to be a better inhibitor than the 2DAG and 2DR based on the results obtained from the MD simulations at 300 K. Furthermore, temperature-dependent MD simulations of the Mpro of nCoV with promising 2DG was performed at 295, 310 and 315 K, and the effective binding with the Mpro of nCoV occurred at 295 K. With the use of DFT calculations, optimized geometry and localization of electron density of the frontier molecular orbitals were calculated. View Full-Text
Keywords: 2-deoxy-D-glucose; main protease of SARS-CoV-2; molecular docking; molecular dynamics simulations; density functional theory calculations 2-deoxy-D-glucose; main protease of SARS-CoV-2; molecular docking; molecular dynamics simulations; density functional theory calculations
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MDPI and ACS Style

Raman, A.P.S.; Kumari, K.; Jain, P.; Vishvakarma, V.K.; Kumar, A.; Kaushik, N.; Choi, E.H.; Kaushik, N.K.; Singh, P. In Silico Evaluation of Binding of 2-Deoxy-D-Glucose with Mpro of nCoV to Combat COVID-19. Pharmaceutics 2022, 14, 135. https://doi.org/10.3390/pharmaceutics14010135

AMA Style

Raman APS, Kumari K, Jain P, Vishvakarma VK, Kumar A, Kaushik N, Choi EH, Kaushik NK, Singh P. In Silico Evaluation of Binding of 2-Deoxy-D-Glucose with Mpro of nCoV to Combat COVID-19. Pharmaceutics. 2022; 14(1):135. https://doi.org/10.3390/pharmaceutics14010135

Chicago/Turabian Style

Raman, Anirudh P.S., Kamlesh Kumari, Pallavi Jain, Vijay K. Vishvakarma, Ajay Kumar, Neha Kaushik, Eun H. Choi, Nagendra K. Kaushik, and Prashant Singh. 2022. "In Silico Evaluation of Binding of 2-Deoxy-D-Glucose with Mpro of nCoV to Combat COVID-19" Pharmaceutics 14, no. 1: 135. https://doi.org/10.3390/pharmaceutics14010135

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