Pyrrolothiazolones as Potential Inhibitors for the nsP2B‐nsP3 Protease of Dengue Virus and Their Mechanism of Synthesis

Abstract

Dengue fever is a severe disease in the present time. Based on literature, there is no effective approved medicine available in the market for the treatment of dengue fever. This fever is spreading rapidly and there is an urgency to find the potential and cost‐effective antiviral compounds for the development of medicine to cure the patients from dengue fever. Different computational and experimental approaches have been tried to find the potential inhibitors for the nsP2B‐nsP3 protease of dengue virus. In the present work, a four component one‐pot reaction was designed to get pyrrolothiazolones & its mechanism of synthesis was studied by density functional theory. A library based on pyrrolothiazolones was created using computational tools. Further, the designed compounds were docked to get the potent inhibitor aginst the nsP2B‐nsP3 protease of dengue virus. Further, different parameters like absorption, distribution, metabolism, excretion and toxicity were applied. DFT analysis of the hit compounds were performed using Gaussian 09. The molecular dynamics simulations study was performed to check the formation of complex between the screened compound and nsP2B‐nsP3 protease of dengue virus. Finally, the molecular mechanics‐Poisson Boltzmann surface area analysis was performed to determine the effective binding for the formation of complex of potent compound with the nsP2B‐nsP3 protease of dengue virus.

In-silico prediction of novel drug-target complex of nsp3 of CHIKV through molecular dynamic simulation

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Xanthene based hybrid analogues to inhibit protease of novel corona Virus: Molecular docking and ADMET studies

“… [2] , [3] , [4] , [5] , [6] , [9] , [12] , [13] , [14] , [15] , [16] , [17] , [19] , [20] , [22] , [24] , [28] , [29] , [30] , [31] , [32] , [35] , [37] , [38] , [39] , [40] , [41] , [42] , [45] , [47] .…”

Kuwanons, Promising inhibitors against the ACE-2, main protease of SARS-CoV-2 and falcipan-2 using molecular docking

“…binding energy. (Kumari, Singh et al 2017;Vishvakarma, Patel et al 2017;Vishvakarma, Singh et al 2017;Kumar, Singh et al 2019;Vishvakarma, Shukla et al 2019;Vishvakarma, Singh et al 2019;Vishvakarma, Kumari et al 2020) This binding energy is due to contribution by the hydrogen bonding, van der Waal's and electrostatic interaction between the amino-acids of the receptor and the small molecules. (Hsu, Chen et al 2011) The visualization of the interaction was studied using Discovery Studio Visualizer.…”