A small carbohydrate molecule against the corona virus?

HPLC analysis of 2-deoxy-D-glucose

What sounds like an unequal David - Goliath battle may be the key to a new therapeutic approach in the fight against COVID-19 disease.

2-deoxy-D-glucose is a glucose molecule in which the hydroxyl group in the 2 position has been replaced by hydrogen.

Chemical structure of 2-Deoxy-D-glucose

By inhibiting glycolysis, 2-deoxy-D-glucose affects carbohydrate metabolism and thus could prevent further proliferation of cells infected with the SARS-CoV-2 virus. Recently, the Drugs Controller General of India approved a 2-deoxy-D-glucose based oral drug for emergency use as an adjunct therapy in moderate to severe COVID-19 patients(1, 2). However, the data from accompanying clinical trials supporting the efficacy of the drug is still incomplete(3).
The inhibition of glycolysis by the molecule has also been discussed in tumor therapy to slow down cell growth or induce cell death. Tumor cells exhibit a higher glycolysis rate(4).

Derivatization was performed with 1-phenyl-3-methyl-5-pyrazolone (PMP).

Chemical structure of PMP

The reaction of PMP with glucose or other sugars is chemically viewed as a base-catalyzed aldol-addition and condensation between an aldehyde and a ketone. Two PMP molecules become added and serve as UV adsorbing chromophores to increase analytical sensitivity in the subsequent HPLC assay(5).

The application Fast carbohydrate analysis (MN application No. 127170) shows the HPLC separation of various PMP derivatized sugars in an UV and ESI-iontrap-MS overlay. The multiple endcapped MACHEREY-NAGEL NUCLEODUR C18 Gravity column has been used. As expected, the 2-deoxy-D-glucose with one OH-group less shows a stronger retention behavior on the C18 phase and elutes accordingly late(6).

Access to application: Fast carbohydrate analysis (MN application No. 127170)

Further examples of drug analysis related to COVID-19

(1) What is 2-deoxy-D-glucose (2-DG) and is it effective against Covid?, The Economic Times, 17 May 2021.
(2) DCGI approves anti-COVID drug developed by DRDO for emergency use". Press Information Bureau, Government of India. 2021-05-08. Retrieved 2021-05-09.
(3) Koshy, Jacob (2021-05-11). "Questions remain on DRDO's COVID drug". The Hindu. ISSN 0971-751X. Retrieved 2021-05-18
(4) Pajak B, Siwiak E, Sołtyka M, Priebe A, Zieliński R, Fokt I, Ziemniak M, Jaśkiewicz A, Borowski R, Domoradzki T, Priebe W. 2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents. Int J Mol Sci. 2019 Dec 29;21(1):234. doi: 10.3390/ijms21010234. PMID: 31905745; PMCID: PMC6982256.
(5) Dr. David Neville, Sugar Molecules in Food (White Paper), https://www.rssl.com.
(6) Rühmann B, Schmidt J, Sieber V, J. Chromatogr. A 1350 (2014) 44 – 50.