{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:51:11Z","timestamp":1791312671406,"version":"4.3.1"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Monkeypox virus (MPXV) is a member of the Orthopoxvirus genus and the Poxviridae family, which instigated a rising epidemic called monkeypox disease. Proteinases are majorly engaged in viral propagation by catalyzing the cleavage of precursor polyproteins. Therefore, proteinase is essential for monkeypox and a critical drug target. In this study, high-throughput virtual screening (HTVS) and molecular dynamics simulation were applied to detect the potential natural compounds against the proteinase of the monkeypox virus. Here, 32,552 natural products were screened, and the top five compounds were selected after implementing the HTVS and molecular docking protocols in series. Gallicynoic Acid F showed the minimum binding score of \u221210.56 kcal\/mole in the extra precision scoring method, which reflected the highest binding with the protein. The top five compounds showed binding scores \u2264\u22128.98 kcal\/mole. These compound complexes were tested under 100 ns molecular dynamics simulation, and Vaccinol M showed the most stable and consistent RMSD trend in the range of 2 \u00c5 to 3 \u00c5. Later, MM\/GBSA binding free energy and principal component analysis were performed on the top five compounds to validate the stability of selected compound complexes. Moreover, the ligands Gallicynoic Acid F and H2-Erythro-Neopterin showed the lowest binding free energies of \u221261.42 kcal\/mol and \u221261.09 kcal\/mol, respectively. Compared to the native ligand TTP-6171 (\u0394GBind = \u221253.86 kcal\/mol), these two compounds showed preferable binding free energy, suggesting inhibitory application against MPXV proteinase. This study proposed natural molecules as a therapeutic solution to control monkeypox disease.<\/jats:p>","DOI":"10.3390\/v15010251","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T03:10:34Z","timestamp":1673838634000},"page":"251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Exploration of Microbially Derived Natural Compounds against Monkeypox Virus as Viral Core Cysteine Proteinase Inhibitors"],"prefix":"10.3390","volume":"15","author":[{"given":"Amit","family":"Dubey","sequence":"first","affiliation":[{"name":"Computational Chemistry & Drug Discovery Division, Quanta Calculus, Greater Noida 201310, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2114-2329","authenticated-orcid":false,"given":"Maha M.","family":"Alawi","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21362, Saudi Arabia"},{"name":"Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah 21362, Saudi Arabia"},{"name":"Infection Control and Environmental Health Unit, King Abdulaziz University Hospital, Jeddah 21362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9130-4031","authenticated-orcid":false,"given":"Thamir A.","family":"Alandijany","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21362, Saudi Arabia"},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0676-8857","authenticated-orcid":false,"given":"Isra M.","family":"Alsaady","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21362, Saudi Arabia"},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Altwaim","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21362, Saudi Arabia"},{"name":"Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah 21362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaresh Kumar","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences, Indian Institute of Information Technology Allahabad, Allahabad 211015, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek Dhar","family":"Dwivedi","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Division, Quanta Calculus, Greater Noida 201310, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1736-181X","authenticated-orcid":false,"given":"Esam Ibraheem","family":"Azhar","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21362, Saudi Arabia"},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.15585\/mmwr.mm6710a5","article-title":"Emergence of Monkeypox\u2014West and Central Africa, 1970\u20132017","volume":"67","author":"Durski","year":"2018","journal-title":"MMWR Morb. 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