{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T12:46:55Z","timestamp":1781700415998,"version":"3.54.5"},"reference-count":107,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>The ongoing pandemic coronavirus disease (COVID-19) caused by a novel corona virus, namely, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has had a major impact on global public health. COVID-19 cases continue to increase across the globe with high mortality rates in immunocompromised patients. There is still a pressing demand for drug discovery and vaccine development against this highly contagious disease. To design and develop antiviral drugs against COVID-19, the main protease (M<jats:sup>pro<\/jats:sup>) has emerged as one of the important drug targets. In this context, the present work explored Jadwar (<jats:italic>Delphinium denudatum<\/jats:italic>)\u2013derived natural alkaloids as potential inhibitors against M<jats:sup>pro<\/jats:sup> of SARS-CoV-2 by employing a combination of molecular docking and molecular dynamic simulation\u2013based methods. Molecular docking and interaction profile analysis revealed strong binding on the M<jats:sup>pro<\/jats:sup> functional domain with four natural alkaloids <jats:italic>viz<\/jats:italic>. panicutine (\u22127.4\u00a0kcal\/mol), vilmorrianone (\u22127.0\u00a0kcal\/mol), denudatine (\u22126.0\u00a0kcal\/mol), and condelphine (\u22125.9\u00a0kcal\/mol). The molecular docking results evaluated by using the MD simulations on 200\u00a0nanoseconds confirmed highly stable interactions of these compounds with the M<jats:sup>pro<\/jats:sup>. Additionally, mechanics\/generalized Born\/Poisson\u2013Boltzmann surface area (MM\/G\/P\/BSA) free energy calculations also affirmed the docking results. Natural alkaloids explored in the present study possess the essential drug-likeness properties, namely, absorption, distribution, metabolism, and excretion (ADME), and are in accordance with Lipinski\u2019s rule of five. The results of this study suggest that these four bioactive molecules, namely, condelphine, denudatine, panicutine, and vilmorrianone, might be effective candidates against COVID-19 and can be further investigated using a number of experimental methods.<\/jats:p>","DOI":"10.3389\/fmolb.2022.898874","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T08:01:12Z","timestamp":1652169672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Potential of Natural Alkaloids From Jadwar (Delphinium denudatum) as Inhibitors Against Main Protease of COVID-19: A Molecular Modeling Approach"],"prefix":"10.3389","volume":"9","author":[{"given":"Anuj","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansi","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Kelvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2971","DOI":"10.1080\/07391102.2020.1758790","article-title":"Moroccan Medicinal Plants as Inhibitors against SARS-CoV-2 Main Protease: Computational Investigations","volume":"39","author":"Aanouz","year":"2020","journal-title":"J. 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