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Obverse Mole Biosci. May 10, 2022;9:898874. doi: 10.3389/fmolb.2022.898874. eCollection 2022.
The ongoing pandemic coronavirus disease (COVID-19) caused by a novel coronavirus, namely severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is having a major impact on global public health. COVID-19 cases continue to rise worldwide, with high mortality rates in immunocompromised patients. There remains an urgent need for drug discovery and vaccine development against this highly contagious disease. To design and develop antiviral drugs against COVID-19, the main protease (Mprofessional) has emerged as one of the most important drug targets. In this context, the present work investigates Jadwar (Delphinium denudatum)-derived natural alkaloids as potential inhibitors against Mprofessional of SARS-CoV-2 using a combination of molecular docking and methods based on molecular dynamics simulation. Molecular docking and interaction profile analysis revealed strong binding to Mprofessional functional domain with four natural alkaloids namely. panicutin (-7.4 kcal/mol), vimorrianone (-7.0 kcal/mol), denudatin (-6.0 kcal/mol) and condelphin (-5.9 kcal/mol). The molecular docking results, evaluated using the MD simulations at 200 nanoseconds, confirmed highly stable interactions of these compounds with the Mprofessional. Additionally, mechanical free energy/generalized Born/Poisson-Boltzmann surface (MM/G/P/BSA) calculations confirmed the docking results. Natural alkaloids examined in the present study possess the essential drug-like properties, namely absorption, distribution, metabolism and excretion (ADME), and comply with Lipinski’s rule of five. The results of this study suggest that these four bioactive molecules, namely condelphin, denudatin, panicutin and vimorrianone, could be effective candidates against COVID-19 and can be further investigated using a range of experimental methods.
PMID:35620478 | PMC:PMC9127362 | DOI:10.3389/fmolb.2022.898874