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

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. reactivity of strongly inhibiting compounds is also analysed by calculating molecular orbital energy descriptors and their band energy gap. Furthermore, pharmacological properties and pharmacokinetics have also been analysed for the compounds. Materials and Methods