{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:56:24Z","timestamp":1790826984265,"version":"4.1.0"},"reference-count":103,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The inhibition mechanism of the main protease (Mpro) of SARS-CoV-2 by ebselen (EBS) and its analog with a hydroxyl group at position 2 of the benzisoselenazol-3(2H)-one ring (EBS-OH) was studied by using a density functional level of theory. Preliminary molecular dynamics simulations on the apo form of Mpro were performed taking into account both the hydrogen donor and acceptor natures of the N\u03b4 and N\u03b5 of His41, a member of the catalytic dyad. The potential energy surfaces for the formation of the Se\u2013S covalent bond mediated by EBS and EBS-OH on Mpro are discussed in detail. The EBS-OH shows a distinctive behavior with respect to EBS in the formation of the noncovalent complex. Due to the presence of canonical H-bonds and noncanonical ones involving less electronegative atoms, such as sulfur and selenium, the influence on the energy barriers and reaction energy of the Minnesota hybrid meta-GGA functionals M06, M06-2X and M08HX, and the more recent range-separated hybrid functional wB97X were also considered. The knowledge of the inhibition mechanism of Mpro by the small protease inhibitors EBS or EBS-OH can enlarge the possibilities for designing more potent and selective inhibitor-based drugs to be used in combination with other antiviral therapies.<\/jats:p>","DOI":"10.3390\/ijms22189792","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T10:31:34Z","timestamp":1631269894000},"page":"9792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Se\u2013S Bond Formation in the Covalent Inhibition Mechanism of SARS-CoV-2 Main Protease by Ebselen-like Inhibitors: A Computational Study"],"prefix":"10.3390","volume":"22","author":[{"given":"Angela","family":"Parise","sequence":"first","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie Chimiche, Universit\u00e0 della Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, CS, Italy"},{"name":"Institut de Chimie Physique UMR8000, Universit\u00e9 Paris-Saclay, CNRS, 91405 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5799-7863","authenticated-orcid":false,"given":"Isabella","family":"Romeo","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie Chimiche, Universit\u00e0 della Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3826-3386","authenticated-orcid":false,"given":"Nino","family":"Russo","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie Chimiche, Universit\u00e0 della Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2386-9078","authenticated-orcid":false,"given":"Tiziana","family":"Marino","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie Chimiche, Universit\u00e0 della Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, CS, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.idc.2019.07.001","article-title":"Severe Acute Respiratory Syndrome: Historical, Epidemiologic, and Clinical Features","volume":"33","author":"Hui","year":"2019","journal-title":"Infect. 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