{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T19:54:04Z","timestamp":1766087644259,"version":"3.40.5"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","issue":"10","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CPB"],"published-print":{"date-parts":[[2021,7,7]]},"abstract":"<jats:sec>\n<jats:title>Background:<\/jats:title>\n<jats:p>COVID-19 caused by SARS-CoV-2 has been declared as a global pandemic\nby WHO. Comprehensive analysis of this unprecedented outbreak may help to fight against the disease\nand may play a pivotal role in decreasing the mortality rate linked with it. Papain-like protease\n(PLpro), a multifunctional polyprotein, facilitates the replication of SARS-CoV-2 and evades it from\nthe host immunological response by antagonizing cytokines, interferons and may be considered as a\npotential drug target to combat the current pandemic.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>Natural moieties obtained from medicinal plants were analysed for their potency to target\nPLpro of SARS-CoV-2 by molecular docking study and were compared with synthetic analogs named\nas remdesivir, chloroquine and favipiravir. The stability of complexes of top hits was analysed by MD\nSimulation, and interaction energy was calculated. Furthermore, average RMSD values were computed\nand deepsite ligand-binding pockets were predicted using Play Molecule. Drug-like-abilities of these\nmoieties were determined using ADMET and bond distance between the ligand and active site was assessed\nto predict the strength of the interaction.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p> Nimbocinol (-7.6 Kcal\/mol) and sage (-7.3 Kcal\/mol) exhibited maximum BA against PLpro\nSARS-CoV-2 as evident from molecular docking study, which was found to be even better than\nremdesivir (-6.1 Kcal\/mol), chloroquine (-5.3 Kcal\/mol) and favipiravir (-5.7 Kcal\/mol). Both nimbocinol-\nPLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation\nof 101ns at 310 K, and potential, kinetic and electrostatic interaction energies were computed,\nwhich was observed to be concordant with results of molecular docking study. RMSD average values\nwere found to be 0.496 \u00b1 0.015 \u00c5 and 0.598 \u00b1 0.023 \u00c5 for nimbocinol and sage, respectively, thus revealing\nthat both the deviation and fluctuations during MD Simulation were observed to be least.\nDeepsite prediction disclosed that both compounds occupied cryptic pockets in receptor and non-bond\ndistance analysis revealed the formation of hydrogen bonds during ligand-receptor interaction. ADMET\nexploration further validated the drug-like properties of these compounds.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p> Present study revealed that active constituents of Azadirachta indica and Salvia officinalis\ncan be potentially used to target SARS-CoV-2 by hindering its replication process.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1389201021999201110204116","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T05:18:46Z","timestamp":1605158326000},"page":"1350-1359","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Computational Evidences of Phytochemical Mediated Disruption of PLpro Driven Replication of SARS-CoV-2: A Therapeutic Approach against COVID-19"],"prefix":"10.2174","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3215-3127","authenticated-orcid":true,"given":"Acharya","family":"Balkrishna","sequence":"first","affiliation":[{"name":"Patanjali Herbal Research Department, Patanajli Research Institute, Haridwar, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4152-7995","authenticated-orcid":true,"given":"Rashmi","family":"Mittal","sequence":"additional","affiliation":[{"name":"Patanjali Herbal Research Department, Patanajli Research Institute, Haridwar, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7562-1731","authenticated-orcid":true,"given":"Vedpriya","family":"Arya","sequence":"additional","affiliation":[{"name":"Patanjali Herbal Research Department, Patanajli Research Institute, Haridwar, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","container-title":["Current Pharmaceutical Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/eurekaselect.com\/article\/download\/187816","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/187816\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eurekaselect.com\/article\/download\/187816","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T04:30:33Z","timestamp":1625805033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/187816\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,7]]},"references-count":0,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,7,7]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/1389201021999201110204116","relation":{},"ISSN":["1389-2010"],"issn-type":[{"type":"print","value":"1389-2010"}],"subject":[],"published":{"date-parts":[[2021,7,7]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2020-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-06","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}