{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T08:40:08Z","timestamp":1769503208232,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of China","award":["2016YFA0501703"],"award-info":[{"award-number":["2016YFA0501703"]}]},{"name":"Ministry of Science and Technology of China","award":["32070662"],"award-info":[{"award-number":["32070662"]}]},{"name":"Ministry of Science and Technology of China","award":["61832019"],"award-info":[{"award-number":["61832019"]}]},{"name":"Ministry of Science and Technology of China","award":["32030063"],"award-info":[{"award-number":["32030063"]}]},{"name":"Ministry of Science 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University","award":["YG2021ZD02"],"award-info":[{"award-number":["YG2021ZD02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The emergence of immune-evading variants of SARS-CoV-2 further aggravated the ongoing pandemic. Despite the deployments of various vaccines, the acquired mutations are capable of escaping both natural and vaccine-induced immune responses. Therefore, further investigation is needed to design a decisive pharmacological treatment that could efficiently block the entry of this virus into cells. Hence, the current study used structure-based methods to target the RBD of the recombinant variant (Deltacron) of SARS-CoV-2, which was used as a model variant. From the virtual drug screenings of various databases, a total of four hits were identified as potential lead molecules. Key residues were blocked by these molecules with favorable structural dynamic features. The binding free energies further validated the potentials of these molecules. The TBE for MNP was calculated to be \u221232.86 \u00b1 0.10 kcal\/mol, for SANC00222 the TBE was \u221223.41 \u00b1 0.15 kcal\/mol, for Liriodenine the TBE was \u221234.29 \u00b1 0.07 kcal\/mol, while for Carviolin the TBE was calculated to be \u221227.67 \u00b1 0.12 kcal\/mol. Moreover, each complex demonstrated distinct internal motion and a free energy profile, indicating a different strategy for the interaction with and inhibition of the RBD. In conclusion, the current study demands further in vivo and in vitro validation for the possible usage of these compounds as potential drugs against SARS-CoV-2 and its variants.<\/jats:p>","DOI":"10.3390\/molecules27217317","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T09:01:42Z","timestamp":1667120502000},"page":"7317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ultra-Large-Scale Screening of Natural Compounds and Free Energy Calculations Revealed Potential Inhibitors for the Receptor-Binding Domain (RBD) of SARS-CoV-2"],"prefix":"10.3390","volume":"27","author":[{"given":"Lisha","family":"Guo","sequence":"first","affiliation":[{"name":"Zhongjing Chinese Medicine College, Nanyang Institute of Technology, 80 Changjiang Road, Nanyang 473004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faryar","family":"Zafar","sequence":"additional","affiliation":[{"name":"Nishtar Medical University, Multan 59341, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nawal","family":"Moeen","sequence":"additional","affiliation":[{"name":"Nawaz Sharif Medical College, Gujrat 50700, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5827-6040","authenticated-orcid":false,"given":"Fahad M.","family":"Alshabrmi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junqi","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Shujait","family":"Ali","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Microbiology, University of Swat, Swat 19120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-0370","authenticated-orcid":false,"given":"Muhammad","family":"Munir","sequence":"additional","affiliation":[{"name":"Division of Biomedical and Life Sciences, Lancaster University, Bailrigg, Lancaster LA1 4YW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbas","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"Zhongjing Research and Industrialization Institute of Chinese Medicine, Zhongguancun Scientific Park, Meixi, Nanyang 473006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4200-7502","authenticated-orcid":false,"given":"Dongqing","family":"Wei","sequence":"additional","affiliation":[{"name":"Division of Biomedical and Life Sciences, Lancaster University, Bailrigg, Lancaster LA1 4YW, UK"},{"name":"Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"Zhongjing Research and Industrialization Institute of Chinese Medicine, Zhongguancun Scientific Park, Meixi, Nanyang 473006, China"},{"name":"Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen 518055, China"},{"name":"State Key Laboratory of Microbial Metabolism, Joint Laboratory of International Laboratory of Metabolic and Developmental Sciences, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. 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