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#Mpro

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Giuseppe Michieli<p><a href="https://mstdn.science/tags/Structural" class="mention hashtag" rel="tag">#<span>Structural</span></a> and <a href="https://mstdn.science/tags/virologic" class="mention hashtag" rel="tag">#<span>virologic</span></a> <a href="https://mstdn.science/tags/mechanism" class="mention hashtag" rel="tag">#<span>mechanism</span></a> of the emergence of <a href="https://mstdn.science/tags/resistance" class="mention hashtag" rel="tag">#<span>resistance</span></a> to <a href="https://mstdn.science/tags/Mpro" class="mention hashtag" rel="tag">#<span>Mpro</span></a> <a href="https://mstdn.science/tags/inhibitors" class="mention hashtag" rel="tag">#<span>inhibitors</span></a> in <a href="https://mstdn.science/tags/SARS" class="mention hashtag" rel="tag">#<span>SARS</span></a>-CoV-2, PNAS: <a href="https://www.pnas.org/doi/abs/10.1073/pnas.2404175121?af=R" target="_blank" rel="nofollow noopener noreferrer" translate="no"><span class="invisible">https://www.</span><span class="ellipsis">pnas.org/doi/abs/10.1073/pnas.</span><span class="invisible">2404175121?af=R</span></a> </p><p>We generated SARS-CoV-2 variants resistant to three SARS-CoV-2 main protease (Mpro) inhibitors (<a href="https://mstdn.science/tags/nirmatrelvir" class="mention hashtag" rel="tag">#<span>nirmatrelvir</span></a>, TKB245, and 5h), by propagating the ancestral SARS-CoV-2WK521WT in VeroE6TMPRSS2 cells with increasing concentrations of each inhibitor and examined their structural and virologic profiles.</p>
Giuseppe Michieli<p><a href="https://mstdn.science/tags/Structural" class="mention hashtag" rel="tag">#<span>Structural</span></a> <a href="https://mstdn.science/tags/basis" class="mention hashtag" rel="tag">#<span>basis</span></a> of <a href="https://mstdn.science/tags/mpro" class="mention hashtag" rel="tag">#<span>mpro</span></a> of <a href="https://mstdn.science/tags/MERS" class="mention hashtag" rel="tag">#<span>MERS</span></a>-CoV bound to antineoplastic <a href="https://mstdn.science/tags/drug" class="mention hashtag" rel="tag">#<span>drug</span></a> <a href="https://mstdn.science/tags/carmofur" class="mention hashtag" rel="tag">#<span>carmofur</span></a>, Biochem Biophys Res Commun.: <a href="https://www.sciencedirect.com/science/article/abs/pii/S0006291X24010052?via%3Dihub" target="_blank" rel="nofollow noopener noreferrer" translate="no"><span class="invisible">https://www.</span><span class="ellipsis">sciencedirect.com/science/arti</span><span class="invisible">cle/abs/pii/S0006291X24010052?via%3Dihub</span></a></p><p>Highlights: <br />* The crystal structure of MERS-CoV Mpro in complex with carmofur.<br />* The structural basis of MERS-CoV Mpro binding to the inhibitor carmofur.<br />* Structural comparison of carmofur with SARS-CoV-2 Mpro and MERS-CoV Mpro.</p>
Giuseppe Michieli<p>&#39;&#39;These results shed light on the mechanisms by which <a href="https://mstdn.science/tags/SARS" class="mention hashtag" rel="tag">#<span>SARS</span></a>-CoV-2 evolves to develop <a href="https://mstdn.science/tags/resistance" class="mention hashtag" rel="tag">#<span>resistance</span></a> to the current generation of <a href="https://mstdn.science/tags/protease" class="mention hashtag" rel="tag">#<span>protease</span></a> <a href="https://mstdn.science/tags/inhibitors" class="mention hashtag" rel="tag">#<span>inhibitors</span></a> and provide the basis for the design of next-generation <a href="https://mstdn.science/tags/Mpro" class="mention hashtag" rel="tag">#<span>Mpro</span></a> inhibitors.&#39;&#39;</p>
Giuseppe Michieli<p>Molecular <a href="https://mstdn.science/tags/mechanisms" class="mention hashtag" rel="tag">#<span>mechanisms</span></a> of <a href="https://mstdn.science/tags/SARS" class="mention hashtag" rel="tag">#<span>SARS</span></a>-CoV-2 <a href="https://mstdn.science/tags/resistance" class="mention hashtag" rel="tag">#<span>resistance</span></a> to <a href="https://mstdn.science/tags/nirmatrelvir" class="mention hashtag" rel="tag">#<span>nirmatrelvir</span></a>, Nature: <a href="https://www.nature.com/articles/s41586-023-06609-0" target="_blank" rel="nofollow noopener noreferrer" translate="no"><span class="invisible">https://www.</span><span class="ellipsis">nature.com/articles/s41586-023</span><span class="invisible">-06609-0</span></a> <a href="https://mstdn.science/tags/research" class="mention hashtag" rel="tag">#<span>research</span></a> <a href="https://mstdn.science/tags/antivirals" class="mention hashtag" rel="tag">#<span>antivirals</span></a> <a href="https://mstdn.science/tags/covid19" class="mention hashtag" rel="tag">#<span>covid19</span></a> <a href="https://mstdn.science/tags/drugs" class="mention hashtag" rel="tag">#<span>drugs</span></a> <a href="https://mstdn.science/tags/mutations" class="mention hashtag" rel="tag">#<span>mutations</span></a> <a href="https://mstdn.science/tags/mpro" class="mention hashtag" rel="tag">#<span>mpro</span></a> <a href="https://mstdn.science/tags/protease" class="mention hashtag" rel="tag">#<span>protease</span></a></p>
Giuseppe Michieli<p>Identification of <a href="https://mstdn.science/tags/SARS" class="mention hashtag" rel="tag">#<span>SARS</span></a>-CoV-2 <a href="https://mstdn.science/tags/Mpro" class="mention hashtag" rel="tag">#<span>Mpro</span></a> <a href="https://mstdn.science/tags/inhibitors" class="mention hashtag" rel="tag">#<span>inhibitors</span></a> containing P1’ 4-fluorobenzothiazole moiety highly active against SARS-CoV-2 <a href="https://www.nature.com/articles/s41467-023-36729-0" target="_blank" rel="nofollow noopener noreferrer" translate="no"><span class="invisible">https://www.</span><span class="ellipsis">nature.com/articles/s41467-023</span><span class="invisible">-36729-0</span></a></p>
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