Penta-1,4-Diene-3-One Oxime Derivatives Strongly Inhibit the Replicase Domain of Tobacco Mosaic Virus: Elucidation Through Molecular Docking and Density Functional Theory Mechanistic Computations

Abstract

Tobacco mosaic virus (TMV) is one of the major concerns to the farmers as it infects several crops of economic importance such as tomato. The mechanism of viral infection in host initiates on the entry of TMV in the host cell and production of a capping enzyme i.e. RNA polymerase. Replication of virus produces multiple mRNAs which further encodes multiple proteins including coat proteins, movement proteins and an RNA-dependent RNA polymerase (RdRp). In the present study, TMV replicase domain has been targeted using a set of novel penta-1,4-diene-3-one oxime derivatives bearing a pyridine moiety. To further assess the reactivity of these compounds against TMV, molecular orbital energy descriptors were calculated using Density Functional Theory (DFT) correlations. The pharmacokinetics and pharmacological properties have also been analysed as the crop yields are to be consumed by the humans. Results revealed that among the 16 derivatives of penta-1,4-diene-3-one oxime, compound C, J, O and P showed the highest inhibitory potential. Reactivity of these compounds was also high, however, only compound C showed effective pharmacokinetics and pharmacological properties. Based on these results, it is concluded that compound C can be used as a potent inhibitor against TMV and the yields produced by a crop will be safe to be consumed by humans.

Insights into the inhibitory potential of selective phytochemicals against Mpro of 2019-nCoV: a computer-aided study

“…In silico methods use computational approaches that are cost-effective and are predictive methods for chemical compounds before carrying out a scientific laboratory experiment [15]. Computational tools have a lot of worth today [16][17][18][19][20]. Meaningful outcomes coming from these computational tools give us basic research in the biomedical regime.…”

Phytochemicals from Selective Plants Have Promising Potential against SARS-CoV-2: Investigation and Corroboration through Molecular Docking, MD Simulations, and Quantum Computations

“…The 3D structures for the phytochemicals were obtained from PubChem ( https://pubchem.ncbi.nlm.nih.gov/ ). The pharmacological and pharmacokinetic properties based on parameters of ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) were evaluated with the help of the SwissADME web server [ 38 ] and PreADMET server [ 39 ], as reported in [ 23 , 26 , 28 , 29 , 31 ]. SwissADME server was utilized for the determination of ADME properties of the phytochemicals, while PreADMET was utilized to assess the druglikeness features and toxicity level of the drug.…”

in silico discovery of potential inhibitors against Dipeptidyl Peptidase-4: A major biological target of Type-2 diabetes mellitus

“…For comparison and validation of the results of present study, various previously reported and experimentally validated compounds were docked with the DPP4. For these dockings, binding affinity was predicted and compared with those of phytochemicals to check if these phytochemicals are competent enough to be used as an inhibitor in the treatment of diabetes mellitus in the future [27,28].…”