Whitefly (Bemisia tabaciGennadius) is a hemipteran phyto polyphagous sucking insect pest which is an important pest of cotton that causes economic losses to the crop by reducing its yield and quality. Ecdysteroids such as 20-hydroxy ecdysone (20-E), play a significant role in larval moulting, development, and reproduction in pterygota insects. Receptor of 20-E, that is Ecdysone Receptor (BtEcR) ofBemisia tabacihas been targeted to prevent fundamental developmental processes. To identify potent inhibitors of BtEcr, 98,072 natural compounds were retrieved from ZINC database. A structure-based virtual screening of these compounds was performed for evaluating their binding affinity to BtEcR, and top two compounds (ZINC08952607 and ZINC04264850) selected based on lowest binding energy. Molecular dynamics simulation (MDS) study was performed for analyzing the dynamics and stability of BtEcR and top-scoring ligand-BtEcR complexes at 50 ns. Besides, g_mmpbsa tool was also used to calculate and analyse the binding free energy of BtEcR-ligand complexes. Compounds ZINC08952607 and ZINC04264850 had shown a binding free energy of −170.156 kJ mol^-1and −200.349 kJ mol^-1in complex with BtEcR respectively. Thus, these compounds can be utilized as lead for the development of environmentally safe insecticides against the whitefly.

Bisphenol A (BPA) is a very important chemical from the commercial perspective. Many useful products are made from it, so its production is increasing day by day. It is widely known that Bisphenol A (BPA) and its analogs are present in the environment and that they enter our body through various routes on a daily basis as we use things made of this chemical in our daily lives. BPA has already been reported to be an endocrine disruptor. Studies have shown that BPA binds strongly to the human estrogen-related receptor gamma (ERRγ) and is an important target of it. This study seeks to understand how it interacts with ERRγ. Molecular docking of BPA and its analogs with ERRγ was performed, and estradiol was taken as a reference. Then, physico-chemical and toxicological analysis of BPA compounds was performed. Subsequently, the dynamic behavior of ERRγ and ERRγ-BPA compound complexes was studied by molecular dynamics simulations over 500 ns, and using this simulated data, their binding energies were again calculated using the MM-PBSA method. We observed that the binding affinity of BPA and its analogs was much higher than that of estradiol, and apart from being toxic, they can be easily absorbed in our body as their physicochemical properties are similar to those of oral medicines. Therefore, this study facilitates the understanding of the structure-activity relationship of ERRγ and BPA compounds and provides information about the key amino acid residues of ERRγ that interact with BPA compounds, which can be helpful to design competitive inhibitors so that we can interrupt the interaction of BPA with ERRγ. In addition, it provides information on BPA and its analogs and will also be helpful in developing new therapeutics.

Background: Porcine reproductive and respiratory syndrome respiratory sickness in weaned and growing pigs, as well as sow reproductive failure, and its infection is regarded as one of the most serious swine illnesses worldwide. Given the current lack of an effective treatment, in this study, we identified natural compounds capable of inhibiting non-structural protein 4 (Nsp4) of the virus, which is involved in their replication and pathogenesis. Results: We screened natural compounds (n = 97,999) obtained from the ZINC database against Nsp4 and selected the top 10 compounds for analysing protein–ligand interactions and physicochemical properties. The five compounds demonstrating strong binding affinity were then subjected to molecular dynamics simulations (100 ns) and binding free energy calculations. Based on analysis, we identified four possible lead compounds that represent potentially effective drug-like inhibitors. Conclusions: These methods identified that these natural compounds are capable of inhibiting Nsp4 and possibly effective as antiviral therapeutics against PRRSV.

Background: Milk provides energy as well as the basic nutrients required by the body. In particular, milk is beneficial for bone growth and development in children. Based on scientific evidence, cattle milk is an excellent and highly nutritious dietary component that is abundant in vitamins, calcium, potassium, and protein, among other minerals. However, the commercial productivity of cattle milk is markedly affected by mastitis. Mastitis is an economically important disease that is characterized by inflammation of the mammary gland. This disease is frequently caused by microorganisms and is detected as abnormalities in the udder and milk. Streptococcus agalactiae is a prominent cause of mastitis. Antibiotics are rarely used to treat this infection, and other available treatments take a long time to exhibit a therapeutic effect. Vaccination is recommended to protect cattle from mastitis. Accordingly, the present study sought to design a multi-epitope vaccine using immunoinformatics. Results: The vaccine was designed to be antigenic, immunogenic, non-toxic, and non-allergic, and had a binding affinity with Toll-like receptor 2 (TLR2) and TLR4 based on structural modeling, docking, and molecular dynamics simulation studies. Besides, the designed vaccine was successfully expressed in E. coli. expression vector (pET28a) depicts its easy purification for production on a larger scale, which was determined through in silico cloning. Further, immune simulation analysis revealed the effectiveness of the vaccine with an increase in the population of B and T cells in response to vaccination. Conclusion: This multi-epitope vaccine is expected to be effective at generating an immune response, thereby paving the way for further experimental studies to combat mastitis.

The HBx protein in Hepatitis B Virus (HBV) is a potential target for anti-liver cancer molecules. Therefore, it is of interest to screen known natural compounds against the HBx protein using molecular docking. However, the structure of HBx is not yet known. Therefore, the predicted structure of HBx using threading in LOMET was used for docking against plant derived natural compounds (curcumin, oleanolic acid, resveratrol, bilobetin, luteoline, ellagic acid, betulinic acid and rutin) by Molegro Virtual Docker. The screening identified rutin with binding energy of -161.65 Kcal/mol. Thus, twenty derivatives of rutin were further designed and screened against HBx. These in silico experiments identified compounds rutin01 (-163.16 Kcal/mol) and rutin08 (- 165.76 Kcal/mol) for further consideration and downstream validation.