Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19.

SARS-CoV-2 is the virus responsible for causing COVID-19 disease in humans, creating the recent pandemic across the world, where lower production of Type I Interferon (IFN-I) is associated with the deadly form of the disease. Membrane protein or SARS-CoV-2 M proteins are known to be the major reason behind the lower production of human IFN-I by suppressing the expression of IFNß and Interferon Stimulated Genes. In this study, 7,832 compounds from 32 medicinal plants of India possessing traditional knowledge linkage with pneumonia-like disease treatment, were screened against the Homology-Modelled structure of SARS-CoV-2 M protein with the objective of identifying some active phytochemicals as inhibitors. The entire study was carried out using different modules of Schrodinger Suite 2020-3. During the docking of the phytochemicals against the SARS-CoV-2 M protein, a compound, ZIN1722 from Zingiber officinale showed the best binding affinity with the receptor with a Glide Docking Score of -5.752 and Glide gscore of -5.789. In order to study the binding stability, the complex between the SARS-CoV-2 M protein and ZIN1722 was subjected to 50 ns Molecular Dynamics simulation using Desmond module of Schrodinger suite 2020-3, during which the receptor-ligand complex showed substantial stability after 32 ns of MD Simulation. The molecule ZIN1722 also showed promising results during ADME-Tox analysis performed using Swiss ADME and pkCSM. With all the findings of this extensive computational study, the compound ZIN1722 is proposed as a potential inhibitor to the SARS-CoV-2 M protein, which may subsequently prevent the immunosuppression mechanism in the human body during the SARS-CoV-2 virus infection. Further studies based on this work would pave the way towards the identification of an effective therapeutic regime for the treatment and management of SARS-CoV-2 infection in a precise and sustainable manner.

Screening of Apoptosis Pathway-Mediated Anti-Proliferative Activity of the Phytochemical Compound Furanodienone against Human Non-Small Lung Cancer A-549 Cells.

Furanodienone (FDN), a major bioactive component of sesquiterpenes produced from Rhizoma Curcumae, has been repeatedly acknowledged for its intrinsic anticancer efficacy against different types of cancer. In this study, we aimed to investigate the cytotoxic potential of furanodienone against human lung cancer (NSCLC A549) cells in vitro, as well as its underlying molecular mechanisms in the induction of apoptosis. Herein, we found that FDN significantly inhibited the proliferation of A549 cells in a dose-dependent manner. In addition, treatment with FDN potentially triggered apoptosis in A549 cells via not only disrupting the nuclear morphology, but by activating capsase-9 and caspase-3 with concomitant modulation of the pro- and antiapoptotic gene expression as well. Furthermore, FDN revealed its competence in inducing cell cycle arrest at G0/G1 phase in A549 cells, which was associated with decreased expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4), along with increased expression of CDK inhibitor p21Cip1. Intriguingly, FDN treatment efficiently downregulated the Wnt signaling pathway, which was correlated with increased apoptosis, as well as cell cycle arrest, in A549 cells. Collectively, FDN might represent a promising adjuvant therapy for the management of lung cancer.

Larvicidal and repellant effects of Jussiaea repens (L.) leaf ethanol extract and its major phyto-constituent against important human vector mosquitoes (Diptera: Culicidae).

Jussiaea repens (L.) leaf ethanol extract (LEE) and its major phyto-compound (MPC) have effects against larvae and adults of dengue, malarial, and filarial vectors. Total larval death rates were recorded from LEE and MPC has significant larval killing activity with LC50/LC90 values of Ae. albopictus, An. stephensi, and Cx. quinquefasciatus that were 118.3/229.9, 116.1/216.8, 114.4/213.5 and 17.7/27.5, 15.6/25.4 and 12.3/21.1 µg/ml, respectively. A best repellent activity was ascertained at 3.057 mg/cm2 concentration of LEE and MPC provided 100% protection upto 240 min against selected human vector mosquitoes (HVMs). The functional groups were confirmed by FT-IR analysis and their presence in ethanol extract and mass spectral analysis: 4-piperidineacetic acid, 1-acetyl-5-ethyl-2-[3-(2-hydroxyethyl]-1H-indol-2-yl]-á-methyl-, methyl ester compound was identified in the LEE. The results obtained suggest that J. repens LEE and its MPC were important and responsible for health protection and control of HVMs.

Bis (Isothiocyanatomethyl) Benzene, A Plant Derived Anti-Neoplastic Compound: Purified from Moringa Oleifera Leaf Extract.

BACKGROUND: Moringa oleifera lam, commonly known as "Sajina", is an indigenous species to India. In our folk medicine, it is used for the treatment of Canker (cancer). The Moringa oleifera leaf extract contains many phyto-compounds, with some being anti-neoplastic in nature. OBJECTIVE: Our preliminary study showed that the leaf extract significantly kills cancer cells compared to normal cells. On searching for the new phyto-compound, Bis-isothiocyanatomethyl) benzene was purified and isolated. METHODS: The sequential process of fractional distillation, column chromatography, followed by TLC and HPLC is performed for purification. Every fraction from each step was tested on HeLa cell line for evaluating the presence of the phyto-compound. RESULTS AND CONCLUSION: FTIR peak analysis of a single phyto-compound shows the presence of thiocyanate group, aromatic carbon group. 1H & 13C NMR peak analysis along with High-resolution mass spectroscopy (HRMS) calculation confirm the chemical structure with IUPAC name [Bis (Isothiocyanatomethyl) benzene]. Previously, Isothiocyanatomethyl- benzene solely or in conjugation with sugar molecule has been reported, but its dimeric form in nature hasnot yet been published anywhere. It shows anticancer activity by retarding cancer cell growth & inhibits carcinogenesis on HeLa, MCF-7, and MDA-MB-231 cell lines by caspase 3 apoptotic pathway and showed comparatively less cytotoxicity to PBMC cell. It shows anticancer activity almost the same as the market available drug Cis-Platin. Therefore, further extrapolating its activity with different concentrations may result in its use as a drug formulation for the treatment of cancer.

Identification of potential leads against 4-hydroxytetrahydrodipicolinate synthase from Mycobacterium tuberculosis.

4-hydroxy-tetrahydrodipicolinate synthase (DHDPS) is an important enzyme needed for the biosynthesis of lysine and many more key metabolites in Mycobacterium tuberculosis (Mtb). Inhibition of DHDPS is supposed to a promising therapeutic target due to its specific role in sporulation, cross-linking of the peptidiglycan polymers and biosynthesis of amino acids. In this work, a known inhibitor-based similarity search was carried out against a natural products database (Super Natural II) towards identification of more potent phyto-inhibitors. Molecular interaction studies were accomplished using three different tools to understand and establish the participation of active site residues as the key players in stabilizing the binding mode of ligands and target protein. The best phyto-compound deduced on the basis of binding affinity was further used as a template to make similarity scan across the PubChem Compound database (score > = 80 %) to get more divesred leads. In this search 5098 hits were obtained that further reduced to 262 after drug-likeness filtration. These phytochemicallike compounds were docked at the active site of DHDPS.Then, those hits selected from docking analysis that showing stronger binding and forming maximum H-bonds with the active site residues (Thr54, Thr55, Tyr143, Arg148 and Lys171). Finally, we predicted one phytochemical compound (SN00003544), two PubChem-compounds (CID41032023, CID54025334) akin to phytochemical molecule showing better interactions in comaprison of known inhibitors of target protein.These findings might be further useful to gain the structural insight into the designing of novel leads against DapA family.