During metastasis, cancer cells transcend from primary site to normal cells area upon attaining epithelial to mesenchymal transition (EMT) causing malignant cancer disease. Increased expression of TGF-β and its receptor ALK5 is an important hallmark of malignant cancer. In the present study, efficacy of curcumin and its analogues as inhibitors of ALK5 (TGFβR-I) receptor was evaluated using in silico approaches. A total of 142 curcumin analogues and curcumin were retrieved from peer reviewed literature and constructed a combinatorial library. Further their drug-likeness was assessed using Molinspiration, cheminformatics and preADMET online servers. The interaction of 142 curcumin analogues and curcumin with ALK5 receptor was studied using Autodock Vina. This study revealed six curcumin analogues as promising ALK5 inhibitors with significant binding energy and H-bonding interaction.
Zinc nanoparticles were synthesized using aqueous leaf extract of Justicia adhatoda L. The characterization of nanoparticles was done by ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), and high-resolution transmission electron microscopy (HR-TEM). The characteristic absorption peak of the UV spectrum was recorded at 379 nm. The FTIR data revealed the possible biomolecules involved in bioreduction and capping of zinc nanoparticles for efficient stabilization. AFM and HR-TEM images have shown that the size of zinc nanoparticles ranges from 55 to 83 nm and they are spherical in shape. The biogenic zinc nanoparticles were evaluated for their toxic effect on mitotic chromosomes of Allium cepa as a model system. Experiments were conducted in triplicate to assay the effect of 25, 50, 75, and 100 % of zinc nanoparticles on mitotic chromosomes at an interval of 6 h duration for 24 h. The investigation revealed that the mitotic index (MI) was decreased with increased concentration of zinc nanoparticles and exposure duration. The results revealed that zinc nanoparticles have induced abnormalities like anaphase bridge formation, diagonal anaphase, C-metaphase, sticky metaphase, laggards, and sticky anaphase at different percentages and times of exposure. It is evident from the observation that mitotic cell division becomes abortive at 100 % treatment of zinc nanoparticles.
SARS-CoV-2 has become a pandemic causing a serious global health concern. The absence of effective drugs for treatment of the disease has caused its rapid spread on a global scale. Similarly to the SARS-CoV, the SARS-CoV-2 is also involved in a complex interplay with the host cells. This infection is characterized by a diffused alveolar damage consistent with the Acute Respiratory Disease Syndrome (ARDS). To explore the complex mechanisms of the disease at the system level, we used a network medicine tools approach. The protein-protein interactions (PPIs) between the SARS-CoV and the associated human cell proteins are crucial for the viral pathogenesis. Since the cellular entry of SARS-CoV-2 is accomplished by binding of the spike glycoprotein binding domain (RBD) to the human angiotensin-converting enzyme 2 (hACE2), a molecule that can bind to the spike RDB-hACE2 interface could block the virus entry. Here, we performed a virtual screening of 55 compounds to identify potential molecules that can bind to the spike glycoprotein and spike-ACE2 complex interface. It was found that the compound ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4-piperidine carboxylate (the S54 ligand) and ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4 piperazine carboxylate (the S55 ligand) forms hydrophobic interactions with Tyr41A, Tyr505B and Tyr553B, Leu29A, Phe495B, respectively of the spike glycoprotein, the hotspot residues in the spike glycoprotein RBD-hACE2 binding interface. Furthermore, molecular dynamics simulations and free energy calculations using the MM-GBSA method showed that the S54 ligand is a stronger binder than a known SARS-CoV spike inhibitor SSAA09E3 (N-(9,10-dioxo-9, 10-dihydroanthracen-2-yl) benzamide).
Communicated by Ramaswamy H. Sarma
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