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The article discusses the inhibition of SARS-CoV-2 3CLpro protease activity by chemically modified tyrosinase from Agaricus bisporus. Natural tyrosinase from Agaricus bisporus showed mild inhibition, leading to the synthesis of different tyrosinase conjugates through chemical modifications. One particular conjugate, tyrosinase and dextran-aspartic acid polymer, showed the highest inhibition of 3CLpro. This new protein also exhibited a significant decrease in viral load in SARS-CoV-2 virus infection studies. The results suggest that these tyrosinase bioconjugates have potential as therapeutic proteins against not only COVID-19 but other viruses as well.
Antiviral compounds are crucial to controlling the SARS-CoV-2 pandemic. Approved drugs have been tested for their efficacy against COVID-19, and new pharmaceuticals are being developed as a complementary tool to vaccines. In this work, a cheap and fast purification method of natural tyrosinase from Agaricus bisporus (AbTyr) fresh mushrooms was developed in order to evaluate the potential of this enzyme as a therapeutic protein by the inhibition of SARS-CoV-2 3CLpro protease activity in vitro. AbTyr showed a mild inhibition of 3CLpro. Thus, different variants of this protein were synthesized through chemical modifications, covalently binding different tailor-made glycans and peptides to the amino terminal groups of the protein. These new tyrosinase conjugates were purified and characterized by circular dichroism and fluorescence spectroscopy analyses, and their stability under different conditions. Then all these tyrosinase conjugates were tested in 3CLpro protease inhibition. From them, the conjugate between tyrosinase and dextran-aspartic acid (6kDa) polymer showed the highest inhibition, with an IC50 of 2.5 µg/ml and IC90 of 5 µg/ml, with no cytotoxicity activity by polymer insertion. Finally, SARS-CoV-2 virus infection was studied, observing that this new AbTyr-Dext6000 protein showed 80% decrease in viral load. These results show the capacity of these tyrosinase bioconjugates as potential therapeutic proteins opening the possibility of extension and applicability against other different viruses.
This article is Open Access
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