The recent outbreak of CoVID-19 is declared as a global public health emergency of international concern by the World Health Organization (WHO). A fresh figure of 2268011 positive cases and 155185 death records (till April 18 th 2020) across the worldwide signify the severity of this viral infection. CoVID-19 infection is a pandemic, surface to surface communicable disease with a case fatality rate of 3.4% as estimated by WHO up to March 3 rd 2020. Unfortunately, the current unavailability of an effective antiviral drug and approved vaccine, worsen the situation more critical. Implementation of an effective preventive measure is the only option left to counteract CoVID-19. Further, a retrospective analysis provides evidence that contemplates the decisive role of preventive measures in controlling severe acute respiratory syndrome (SARS) outbreak in 2003. A statistical surveillance report of WHO reflects, maintaining a coherent infection, prevention and control guideline resulted in a 30% reduction in healthcare-associated infections. The effectiveness of preventive measures completely relies on the strength of surface disinfectants, the composition of hand sanitizer, appropriate material for the manufacture of personal protective equipment (PPE). This review enlightens the various preventive measures such as a suitable selection of surface disinfectants, appropriate hand sanitization, and empowering the PPE that could be a potential intervention to fight against CoVID-19.

Noscapine and its derivatives are important microtubule-interfering agents shown to have potent anti-tumor activity. The binding free energies (ΔG (bind)) of noscapinoids computed using linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model were in agreement with the experimental ΔG (bind) with average root mean square error of 0.082 kcal/mol. This LIE-SGB model guided us in designing a novel derivative of noscapine, amino-noscapine [(S)-3-((R)-9-amino-4-methoxy-6-methyl-5,6,7,8-tetrahydro [1, 3] dioxolo[4,5-g]isoquinolin-5-yl)-6,7-dimethoxy isobenzo-furan-1(3H)-one] that has higher tubulin binding activity (predicted ΔG (bind) = -6.438 kcal/mol and experimental ΔG (bind) = -6.628 kcal/mol) than noscapine, but does not significantly change the total extent of the tubulin subunit/polymer ratio. The modes of interaction of amino-noscapine with the binding pocket of tubulin involved three hydrogen bonds and are distinct compared to noscapine which involved only one hydrogen bond. Also the patterns of non-bonded interactions are albeit different between both the lignads. The 'blind docking' approach (docking of ligand with different binding sites of a protein and their evaluations) as well as the reasonable accuracy of calculating ΔG (bind) using LIE-SGB model constitutes the first evidence that this class of compounds binds to tubulin at a site overlapping with colchicine-binding site or close to it. Our results revealed that amino-noscapine has better anti-tumor activity than noscapine.

Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol) than the parent compound, noscapine (-5.505 kCal/mol) and its existing derivatives (-5.563 to -6.412 kCal/mol). Free energy (ΔG bind) calculations based on the linear interaction energy (LIE) empirical equation utilizing Surface Generalized Born (SGB) continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol). Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol). The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl) noscapine (6f) binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM), which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM) and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM). All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents.

We have previously discovered the tubulin-binding anti-cancer properties of noscapine and its derivatives (noscapinoids). Here, we present three lines of evidence that noscapinoids bind at or near the well studied colchicine binding site of tubulin: 1) In silico molecular docking studies of Br-noscapine and noscapine yield highest docking score with the well characterised colchicine-binding site from the co-crystal structure; 2) the molecular mechanics-generalized Born/surface area (MM-GB/SA) scoring results ΔΔGbind-cald for both noscapine and Br-noscapine (3.915 and 3.025 kcal/mol) are in reasonably good agreement with our experimentally determined binding affinity (ΔΔGbind-expt of 3.570 and 2.988 kcal/mol, derived from Kd values); and 3) Br-noscapine competes with colchicine binding to tubulin. The simplest interpretation of these collective data is that Br-noscapine binds tubulin at a site overlapping with, or very close to colchicine-binding site of tubulin. Although we cannot rule out a formal possibility that Br-noscapine might bind to a site distinct and distant from the colchicine-binding site that might negatively influence the colchicine binding to tubulin.

At the booting stage of development, rice (Oryza sativa L.) plants were treated with chemicals that either inhibited the action or synthesis of ethylene, or produced ethylene. Inhibitors of ethylene action (AgNO3) and synthesis [uniconazole, paclobutrazol, Co(NO3)2] promoted grain filling and quality of the kernels of the basal spikelets of the panicle, while the ethylene-releasing substance CEPA (2-chloroethylphosphonic acid) depressed these characteristics further. The inhibitors depressed the concentration of ethylene of the basal primary branches, but CEPA increased it above the control during the period of grain filling. The treatments were not effective on the superior apical spikelets of the panicle. The ethylene inhibitors improved starch synthesis in the kernels of the basal spikelets, but CEPA reduced it significantly, resulting in accumulation of soluble carbohydrates in the kernels. During the period of grain filling, sucrose synthase activity was higher than that of invertase in the kernels. Activities of sucrose synthase and invertase were higher in the apical than in the basal kernel. The ethylene inhibitors increased activities of both enzymes only in the basal kernel, whereas CEPA reduced activities significantly. Together, the results indicate that starch filling and grain quality of the basally positioned under-developed rice kernels can be affected by ethylene, and that key enzymes of sucrose metabolism are also affected in the process.

Ginger (Zingiber officinale Roscoe) is an economically important plant, valued all over the world. The existing variation among 16 promising cultivars as observed through differential rhizome yield (181.9 to 477.3 g) was proved to have a genetic basis using different genetic markers such as karyotype, 4C nuclear DNA content and random amplified polymorphic DNA (RAPD). The karyotypic analysis revealed a differential distribution of A, B, C, D and E type of chromosomes among different cultivars as represented by different karyotype formulas. A significant variation of 4C DNA content was recorded in ginger at an intraspecific level with values ranging from 17.1 to 24.3 pg. RAPD analysis revealed a differential polymorphism of DNA showing a number of polymorphic bands ranging from 26 to 70 among 16 cultivars. The RAPD primers OPC02, OPA02, OPD20 and OPN06 showing strong resolving power were able to distinguish all 16 cultivars. The extent of genetic diversity among these cultivars was computed through parameters of gene diversity, sum of allele numbers per locus and Shannon's information indices. Cluster analysis, Nei's genetic similarity and genetic distances, distribution of cultivars into special distance classes and principal coordinate analysis and the analysis of molecular variance suggested a conspicuous genetic diversity among different cultivars studied. The genetic variation thus detected among promising cultivars of ginger has significance for ginger improvement programs.

Picrorhiza kurroa, has become an endangered medicinal herb due to excessive utilization, therefore it necessitates the understanding of biology and molecular basis of major chemical constituents i.e. Picroside-I (P-I) and Picroside-II (P-II). Estimation of P-I and P-II in different tissues of P. kurroa showed that shoots contain only P-I whereas P-II is present only in roots. Differential conditions with varying concentrations of P-I (0-27 μg/mg) and P-II (0-4 μg/mg) were selected. Four genes of MEP pathway; DXPS, ISPD, ISPE, MECPS and one gene of MVA pathway PMK showed elevated levels of transcripts in shoots (57-166 folds) and stolons (5-15 folds) with P-I contents 0-27 μg/mg and 2.9-19.7 μg/mg, respectively. Further HDS and DXPR genes of MEP pathway showed higher expression ~9-12 folds in roots having P-II (0-4 μg/mg). The expression of ISPH and ISPE was also high ~5 folds in roots accumulating P-II. GDPS was the only gene with high transcript level in roots (9 folds) and shoots (20 folds). Differential biosynthesis and accumulation of picrosides would assist in regulating quality of plant material for herbal drug formulations.

Primary branch development of the rice panicle was in the order of a basipetal sequence from the top to the bottom at the time of anthesis. Delayed development of spikelets on the proximal branches of the panicle resulted in reduced grain filling. Two experiments were carried out to manipulate growth and development of the proximal spikelets with exogenous application of chemicals regulating formation or action of ethylene. In the first experiment, inhibitors of ethylene synthesis (cobalt) and action (silver) improved grain biomass and specific gravity of the basal spikelets, while 2-chloroethylphosphonic acid (CEPA) depressed these parameters significantly. In the second experiment, the ethylene synthesis inhibitor 1-aminoethoxyvinylglycine (AVG) promoted spikelet development on the basal primary branches and improved their survival and grain biomass. On the contrary, the ethylene precursor 1-aminocyclopropane-1- carboxylic acid (ACC) inhibited growth and development of these spikelets. The action of AVG was reversed when ACC was applied in combination with AVG. In both experiments, the chemicals did not influence growth and development of the superior spikelets on the apical primary branches of the panicle. Depression of growth and development by CEPA or ACC coincided with a concomitant rise in soluble carbohydrate concentration of the spikelets, whereas treatments with ethylene inhibitors decreased the concentration of the materials. The role of ethylene in metabolic dominance of the apical spikelets and its impact on grain yield of rice panicles is discussed.