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The rational design of an efficient biocatalyst for the phosphoribosylation of antiviral pyrazine-2- carboxamide derivatives

The antiviral T-1105 and T-705 (Favipiravir) compounds are inactive prodrugs that undergo metabolic transformation into the active form through phosphoribosylation in vivo. The efficiency of this process in human cells is very low, making the production of the phosphoribosylated pyrazine-2-carboxamide derivatives in vitro is a worthy challenge.

The researchers from Dep. of Biotechnology of IBCh RAS, along with colleagues from MSU and FSRC “Crystallography and Photonics” RAS report the rational design of an efficient biocatalyst based on the hypoxanthine-guanine phosphoribosyltransferase from T. thermophilus (TthHGPRT). The rational design of TthHGPRT active site has allowed to engineer the D106G/Y155W mutant with a 325-fold increase in the rate of synthesis of T-705-riboside-5’-phosphate and 125-fold – T-1105-riboside-5’-phosphate. The reported results can become the basis for the new technologies of enzymatic production of antiviral compounds.

The results are published in ACS Catalysis.

february 27