{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:04:43Z","timestamp":1790316283731,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Pharmacological strategies to lower the viral load among patients suffering from severe diseases were researched in great detail during the SARS-CoV-2 outbreak. The viral protease Mpro (3CLpro) is necessary for viral replication and is among the main therapeutic targets proposed, thus far. To stop the pandemic from spreading, researchers are working to find more effective Mpro inhibitors against SARS-CoV-2. The 33.8 kDa Mpro protease of SARS-CoV-2, being a nonhuman homologue, has the possibility of being utilized as a therapeutic target against coronaviruses. To develop drug-like compounds capable of preventing the replication of SARS-main CoV-2\u2019s protease (Mpro), a computer-aided drug design (CADD) approach is extremely viable. Using MOE, structure-based virtual screening (SBVS) of in-house and commercial databases was carried out using SARS-CoV-2 proteins. The most promising hits obtained during virtual screening (VS) were put through molecular docking with the help of MOE. The virtual screening yielded 3\/5 hits (in-house database) and 56\/66 hits (commercial databases). Finally, 3\/5 hits (in-house database), 3\/5 hits (ZINC database), and 2\/7 hits (ChemBridge database) were chosen as potent lead compounds using various scaffolds due to their considerable binding affinity with Mpro protein. The outcomes of SBVS were then validated using an analysis based on molecular dynamics simulation (MDS). The complexes\u2019 stability was tested using MDS and post-MDS. The most promising candidates were found to exhibit a high capacity for fitting into the protein-binding pocket and interacting with the catalytic dyad. At least one of the scaffolds selected will possibly prove useful for future research. However, further scientific confirmation in the form of preclinical and clinical research is required before implementation.<\/jats:p>","DOI":"10.3390\/bioengineering10010100","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T01:32:26Z","timestamp":1673487146000},"page":"100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["In-Silico Lead Druggable Compounds Identification against SARS COVID-19 Main Protease Target from In-House, Chembridge and Zinc Databases by Structure-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1620-8610","authenticated-orcid":false,"given":"Mehreen","family":"Ghufran","sequence":"first","affiliation":[{"name":"Department of Pathology, Medical Teaching Institution Bacha Khan Medical College (BKMC) Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehran","family":"Ullah","sequence":"additional","affiliation":[{"name":"District Medical Officer, Sehat Sahulat Program (SSP), KPK, Mardan 23200, Pakistan"},{"name":"Mardan Medical Complex (MMC) Mardan, Medical Teaching Institution Bacha Khan Medical College (BKMC), Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haider Ali","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabreen","family":"Ghufran","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4299-2445","authenticated-orcid":false,"given":"Muhammad","family":"Ayaz","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Malakand, Chakdara 18000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Siddiq","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3774-9907","authenticated-orcid":false,"given":"Syed Qamar","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sarhad University of Science and technology, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-6540","authenticated-orcid":false,"given":"Syed Shams ul","family":"Hassan","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"Department of Natural Product Chemistry, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3236-1292","authenticated-orcid":false,"given":"Simona","family":"Bungau","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.46234\/ccdcw2020.032","article-title":"The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)\u2014China, 2020","volume":"2","author":"Team","year":"2020","journal-title":"China CDC Wkly."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gorbalenya, A.E., Baker, S.C., Baric, R., Groot, R.J.d., Drosten, C., Gulyaeva, A.A., Haagmans, B.L., Lauber, C., Leontovich, A.M., and Neuman, B.W. 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