{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:56:15Z","timestamp":1780055775465,"version":"3.54.0"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160389"],"award-info":[{"award-number":["82160389"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["GuiKe AB19245038"],"award-info":[{"award-number":["GuiKe AB19245038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022YFC2305001C"],"award-info":[{"award-number":["2022YFC2305001C"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangxi Science and Technology Plan","award":["82160389"],"award-info":[{"award-number":["82160389"]}]},{"name":"Guangxi Science and Technology Plan","award":["GuiKe AB19245038"],"award-info":[{"award-number":["GuiKe AB19245038"]}]},{"name":"Guangxi Science and Technology Plan","award":["2022YFC2305001C"],"award-info":[{"award-number":["2022YFC2305001C"]}]},{"name":"National Key R&amp;D Program of China","award":["82160389"],"award-info":[{"award-number":["82160389"]}]},{"name":"National Key R&amp;D Program of China","award":["GuiKe AB19245038"],"award-info":[{"award-number":["GuiKe AB19245038"]}]},{"name":"National Key R&amp;D Program of China","award":["2022YFC2305001C"],"award-info":[{"award-number":["2022YFC2305001C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The monkeypox outbreak has become a global public health emergency. The lack of valid and safe medicine is a crucial obstacle hindering the extermination of orthopoxvirus infections. The identification of potential inhibitors from natural products, including Traditional Chinese Medicine (TCM), by molecular modeling could expand the arsenal of antiviral chemotherapeutic agents. Monkeypox DNA topoisomerase I (TOP1) is a highly conserved viral DNA repair enzyme with a small size and low homology to human proteins. The protein model of viral DNA TOP1 was obtained by homology modeling. The reliability of the TOP1 model was validated by analyzing its Ramachandran plot and by determining the compatibility of the 3D model with its sequence using the Verify 3D and PROCHECK services. In order to identify potential inhibitors of TOP1, an integrated library of 4103 natural products was screened via Glide docking. Surface Plasmon Resonance (SPR) was further implemented to assay the complex binding affinity. Molecular dynamics simulations (100\u2009ns) were combined with molecular mechanics Poisson\u2013Boltzmann surface area (MM\/PBSA) computations to reveal the binding mechanisms of the complex. As a result, three natural compounds were highlighted as potential inhibitors via docking-based virtual screening. Rosmarinic acid, myricitrin, quercitrin, and ofloxacin can bind TOP1 with KD values of 2.16 \u03bcM, 3.54 \u03bcM, 4.77 \u03bcM, and 5.46 \u03bcM, respectively, indicating a good inhibitory effect against MPXV. The MM\/PBSA calculations revealed that rosmarinic acid had the lowest binding free energy at \u221216.18 kcal\/mol. Myricitrin had a binding free energy of \u221213.87 kcal\/mol, quercitrin had a binding free energy of \u22129.40 kcal\/mol, and ofloxacin had a binding free energy of \u22129.64 kcal\/mol. The outputs (RMSD\/RMSF\/Rg\/SASA) also indicated that the systems were well-behaved towards the complex. The selected compounds formed several key hydrogen bonds with TOP1 residues (TYR274, LYS167, GLY132, LYS133, etc.) via the binding mode analysis. TYR274 was predicted to be a pivotal residue for compound interactions in the binding pocket of TOP1. The results of the enrichment analyses illustrated the potential pharmacological networks of rosmarinic acid. The molecular modeling approach may be acceptable for the identification and design of novel poxvirus inhibitors; however, further studies are warranted to evaluate their therapeutic potential.<\/jats:p>","DOI":"10.3390\/molecules28031444","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T01:40:25Z","timestamp":1675388425000},"page":"1444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Potential Inhibitors of Monkeypox Virus Revealed by Molecular Modeling Approach to Viral DNA Topoisomerase I"],"prefix":"10.3390","volume":"28","author":[{"given":"Xiaopeng","family":"Hu","sequence":"first","affiliation":[{"name":"Biosafety Level-3 Laboratory, Life Sciences Institute & Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanqi","family":"An","sequence":"additional","affiliation":[{"name":"Biosafety Level-3 Laboratory, Life Sciences Institute & Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiemei","family":"Chu","sequence":"additional","affiliation":[{"name":"Biosafety Level-3 Laboratory, Life Sciences Institute & Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9788-5826","authenticated-orcid":false,"given":"Bingyu","family":"Liang","sequence":"additional","affiliation":[{"name":"Biosafety Level-3 Laboratory, Life Sciences Institute & Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Liao","sequence":"additional","affiliation":[{"name":"Biosafety Level-3 Laboratory, Life Sciences Institute & Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Biosafety Level-3 Laboratory, Life Sciences Institute & Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Lin","sequence":"additional","affiliation":[{"name":"Biosafety Level-3 Laboratory, Life Sciences Institute & Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ye","sequence":"additional","affiliation":[{"name":"Biosafety Level-3 Laboratory, Life Sciences Institute & Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7534-5124","authenticated-orcid":false,"given":"Hao","family":"Liang","sequence":"additional","affiliation":[{"name":"Biosafety Level-3 Laboratory, Life Sciences Institute & Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alakunle, E., Moens, U., Nchinda, G., and Okeke, M. 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