Fighting SARS-CoV-2

Fighting SARS-CoV-2

Published on 10/11/2020

Fighting COVID-19 by modifying essential viral proteins via glycation through methylglyoxal – a reactive carbonyl compound known from the Maillard reaction. Read on to find out more!

A recent publication highlights protein modification by methylglyoxal (MG) – a dicarbonyl known in the context of the Maillard reaction – as a potential approach to diminish the activity of the SARS-CoV-2 virus. The global pandemic of COVID-19 counts almost 51 million recorded cases including more than one million deaths as of November 11th, 2020 (www.WHO.org). To push the urgent requirement for an anti-viral treatment forward, one approach benefiting from a high degree of investigation is to repurpose well-established drugs and strategies.

One option for improved drug therapy is to increase levels of endogenous reactive metabolites to damage the viral proteome. Among those are reactive oxygen species (ROS), as well as the reactive glycating agent methylglyoxal (MG). ROS can oxidize cysteine residues in proteins to cystine and cysteine sulfenic and sulfonic acids. In the case of MG, mainly arginine residues are targeted and glycated to the hydroimidazolone MG-H1 (HAA3000), resulting in a loss of charge and consequently a loss of all related electrostatic interactions. Typically, this glycation also leads to resistance to proteolytic cleavage close to the site of modification.

Possible modifications of arginine by methylglyoxal.

The modification of amino acids might lead to changes in a protein’s three-dimensional structure and thus alter its activity  or lead to a loss of function. Sequence-based analysis of the SARS-CoV-2 proteome revealed that particularly arginine residues, but not cysteines are accumulated in certain functional domains. This suggests that SARS-CoV-2 is rather resistant to oxidative agents, but sensitive to MG, indicating that modifications of those arginine residues might lead to an inactivation of the virus and virucidal activity. Importantly, studies revealed that crucial arginines are also present in functional domains of the viral spike protein. Thus, dysfunction of the spike protein caused by the modification of arginine residues might block cell fusion and inhibit virion entry, and thus improve the host immune response to the virus.


For your research purposes within this context, Iris Biotech offers a range of methylglyoxal-derived Maillard reaction products, e.g. Argpyrimidine (FAA5530), Glyoxal-hydroimidazolone (HAA2970), Methylglyoxal-hydroimidazolone (HAA3000) and various more (see related products).

References:

  • Vulnerabilities of the SARS-CoV-2 Virus to Proteotoxicity-Opportunity for Repurposed Chemotherapy of COVID-19 Infection; M. S. Al-Motawa, H. Abbas, P. Wijten, A. de la Fuente, M. Xue, N. Rabbani, and P. J. Thornalley; Front. Pharmacol. 2020; https://doi.org/10.3389/fphar.2020.585408.
  • Methylglyoxal alters the function and stability of critical components of the protein quality control; C. F. Bento, F. Marques, R. Fernandes, P. Pereira; PLoS ONE 2010; 5: e13007. https://doi.org/10.1371/journal.pone.0013007.
  • Inactivated or damaged? Comparing the effect of inactivation methods on influenza virions to optimize vaccine production; J. Herrera-Rodriguez, A. Signorazzi, M. Holtrop, J. de Vries-Idema, A. Huckeriede; Vaccine 2019; 37: 1630-1637. https://doi.org/10.1016/j.vaccine.2019.01.086.
  • Advanced Glycation End Products (AGEs); H. G. Akıllıoğlu, V. Gökmen; Chemical Hazards in Thermally-Processed Foods 2019; 121-151. https://doi.org/10.1007/978-981-13-8118-8_6.
  • Modulation of collagen proteolysis by chemical modification of amino acid side-chains in acellularized arteries. P. F. Gratzer, J. M. Lee, J. P. Santerre; Biomaterials 2004; 25: 2081-2094. https://doi.org/10.1016/j.biomaterials.2003.08.059.
  • Role of Advanced Glycation End Products in Hypertension and Atherosclerosis: Therapeutic Implications; S. Vasdev; Cell Biochem. Biophys. 2007; 49: 48-63. https://doi.org/10.1007/s12013-007-0039-0.
  • Role of methylglyoxal in essential hypertension; S. Vasdev, J. Stuckless; Int. J. Angiol. 2010; 19: e58-65. https://doi.org/10.1055/s-0031-1278375.



Related Products
    1. Structure image for (Boc-L-Cys-OH)2
      (Boc-L-Cys-OH)2

      Product code: BAA5390

      Starting at $128.25

    2. Structure image for Fmoc-L-CML(OtBu)(Boc)-OH
      Fmoc-L-CML(OtBu)(Boc)-OH

      Product code: FAA3620

      Starting at $843.75

    3. Structure image for Fmoc-L-CEL(OtBu)(Boc)-OH
      Fmoc-L-CEL(OtBu)(Boc)-OH

      Product code: FAA3630

      Starting at $337.50

    4. Structure image for G-H1
      G-H1

      Product code: HAA2970

      Starting at $249.75

    5. Structure image for MG-H1 (TFA salt)
      MG-H1 (TFA salt)

      Product code: HAA3000

      Starting at $195.75

    6. Structure image for G-H1-13C2
      G-H1-13C2

      Product code: HAA2971

      Starting at $587.25

    7. Structure image for G-H2
      G-H2

      Product code: HAA3270

      Starting at $371.25

    8. Structure image for G-H3 (TFA salt)
      G-H3 (TFA salt)

      Product code: HAA3280

      Starting at $297.00

    9. Structure image for MG-H2
      MG-H2

      Product code: HAA3320

      Starting at $236.25

    10. Structure image for MG-H3 (TFA salt)
      MG-H3 (TFA salt)

      Product code: HAA3330

      Starting at $297.00

    11. Structure image for Fmoc-L-Lys(Boc,Fructose)-OH
      Fmoc-L-Lys(Boc,Fructose)-OH

      Product code: FAA5540

      Starting at $337.50

    12. Structure image for Fmoc-L-Argpyrimidine(Pbf,TBMS)-OH
      Fmoc-L-Argpyrimidine(Pbf,TBMS)-OH

      Product code: FAA5530

      Starting at $337.50

    13. Fmoc-L-Pyrraline(TBS)-OH
      Fmoc-L-Pyrraline(TBS)-OH

      Product code: FAA7520.1000

      $1,620.00
    14. Structure image for MG-H1-d3 (Acetate salt)
      MG-H1-d3 (Acetate salt)

      Product code: HAA3002

      Starting at $405.00

    15. Structure image for Fmoc-L-Cys(SO2Mob)-OH
      Fmoc-L-Cys(SO2Mob)-OH

      Product code: FAA8410

      Starting at Please inquire