Issue 38, 2021

The interactions of folate with the enzyme furin: a computational study


Entrance of coronavirus into cells happens through the spike proteins on the virus surface, for which the spike protein should be cleaved into S1 and S2 domains. This cleavage is mediated by furin, a member of the proprotein convertases family, which can specifically cleave Arg-X-X-Arg↓ sites of the substrates. Here, folate (folic acid), a water-soluble B vitamin, is introduced for the inhibition of furin activity. Therefore, molecular insight into the prevention of furin activity in the presence of folic acid derivatives is presented. To this aim, molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations were performed to clarify the inhibitory mechanism of these compounds. In this regard, molecular docking studies were conducted to probe the furin binding sites of folic acid derivatives. The MD simulation results indicated that these drugs can efficiently bind to the furin active site. While the folic acid molecule tended to be positioned slightly towards the Glu271, Tyr313, Ala532, Gln488, and Asp530 amino acids of furin at short and long ranges, the folinic acid molecule interacted with Glu271, Ser311, Arg490, Gln488, and Lys499 amino acids. Consequently, binding free energy calculations illustrated that folic acid (−27.90 kcal mol−1) has better binding in comparison with folinic acid (−12.84 kcal mol−1).

Graphical abstract: The interactions of folate with the enzyme furin: a computational study

Article information

Article type
27 Apr 2021
28 Jun 2021
First published
06 Jul 2021
This article is Open Access
Creative Commons BY license

RSC Adv., 2021,11, 23815-23824

The interactions of folate with the enzyme furin: a computational study

Z. Sheybani, M. Heydari Dokoohaki, M. Negahdaripour, M. Dehdashti, H. Zolghadr, M. Moghadami, S. M. Masoompour and A. R. Zolghadr, RSC Adv., 2021, 11, 23815 DOI: 10.1039/D1RA03299B

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