Abstract:
The Newcastle Disease Virus (NDV), primary pathogen responsible for Newcastle Disease
(ND) infection in poultry, is classified as an avian paramyxovirus type I and possesses an
outer protective layer. The viral genome consists of a single-stranded RNA molecule with a
negative-sense orientation, measuring around 15.2 kilobases in length. This RNA molecule
encodes a total of six distinct proteins. Four structural proteins including HN, F, M and NP
are regarded as promising therapeutic targets owing to their crucial role in viral replication
cycle. There are currently no NDV specific antiviral agents/therapeutics available in the
poultry industry and due to the ineffectiveness of commercial live attenuated vaccine,
outbreaks of this disease are frequently observed within the chicken business, resulting in
substantial economic repercussions. The Thiazolidinedione based drugs known for their anti diabetic, anti-microbial, anti-tumor, anti-viral, anti-inflammatory, and anti-cancer properties
have been repurposed as anti-NDV drugs through computational methods. Nevertheless,
there has not been a single study about these Thiazolidinedione based drugs reported against
NDV. Therefore, the present study has been conducted to explore the inhibitory potential of
10 Thiazolidinedione based drugs against four essential structural proteins of Newcastle
Disease Virus i.e., HN, F, M and NP. Significant and encouraging outcomes have been
shown for the following compounds: HN/Troglitazone (-9.2 kcal/mol), HN/Englitazone (-9.1
kcal/mol), NP/Troglitazone (-8.6 kcal/mol), and F/Balaglitazone (-7.8 kcal/mol). In a similar
vein, the compounds M/Rosiglitazone and M/Ciglitazone have demonstrated potential
positive results, with respective binding energies of -8.4 kcal/mol and -8.1 kcal/mol. The
structural flexibility of the HN/Troglitazone, HN/Englitazone, NP/Troglitazone, and
F/Balaglitazone docking complexes was confirmed by MD simulations, as evidenced by the
root mean square fluctuation (RMSF) values below 5Å. The study's findings indicated that
Troglitazone, Englitazone, Balaglitazone, Rosiglitazone, and Ciglitazone have the most
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effective antiviral therapeutic potential against Newcastle Disease infections. Additional in
vitro and in vivo evaluation to better understand the molecular complexity of therapeutic and
antiviral capabilities will increase researchers' chances of finding innovative therapeutics
throughout the drug development process.
