Molecular Docking Approach for Biological Interaction of Green Synthesized Nanoparticles.

In recent years, significant progress has been made in the subject of nanotechnology, with a range of methods developed to synthesize precise-sized and shaped nanoparticles according to particular requirements. Often, the nanoparticles are created by employing dangerous reducing chemicals to reduce metal ions into uncharged nanoparticles. Green synthesis or biological approaches have been used recently to circumvent this issue because biological techniques are simple, inexpensive, safe, clean, and extremely productive. Nowadays, much research is being conducted on how different kinds of nanoparticles connect to proteins and nucleic acids using molecular docking models. Therefore, this review discusses the most recent advancements in molecular docking capacity to predict the interactions between various nanoparticles (NPs), such as ZnO, CuO, Ag, Au, and Fe3O4, and biological macromolecules.

Synthesis of Carvacrol Derivatives as Potential New Anticancer Agent against Lung Cancer.

Lung cancer remains a major public health concern among all cancer diseases due to the toxicity and side-effects of the available commercially synthesized drugs. Natural product-derived synthesized anticancer drugs are now of promising interest to fight against cancer death. Carvacrol is a major component of most essential oil-bearing plants with potential pharmacological activity, especially against various cancer cell lines. Among the other organometallic compounds, copper complexes have been reported to be effective anticancer agents against various cancer cell lines, especially lung and leukemia cancers, due to the nontoxic nature of copper in normal cells since it is an endogenic metal. In this study, we synthesized three carvacrol derivatives, i.e., carvacrol aldehyde, Schiff base, and copper-Schiff base complex, through an established synthesis protocol and characterized the synthesized product using various spectroscopic techniques. The synthesized derivatives were evaluated for in vitro cytotoxic activity against different cancer cell lines, including human lung cancer (A549) and human fibroblast (BALB-3T3). Our findings showed that the copper-Schiff base complex derived from carvacrol inhibited the proliferation and migration of the A549 cell lines in a dose-dependent manner. This activity might be due to the inhibition of cell proliferation and migration at the G2/M cell-cycle phase, as well as apoptosis, possibly through the activation of the mitochondrial apoptotic pathway. To our knowledge, this is the first report on the activity of the copper-Schiff base complex of carvacrol against A549 cell lines. Our result highlights that a new synthesized copper complex from carvacrol could be a novel potential drug in the treatment of lung cancer.

Computational profiling of natural compounds as promising inhibitors against the spike proteins of SARS-CoV-2 wild-type and the variants of concern, viral cell-entry process, and cytokine storm in COVID-19.

The continuous spread and evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the rapid surge in infection cases in the coronavirus disease 2019 (COVID-19) evoke a dire need for effective therapeutics. In this study, we explored the inhibitory potential of a library of 605 phytocompounds, selected from Indian medicinal plants with reported antiviral and anti-inflammatory activities, against the receptor-binding domain of spike proteins of the SARS-CoV-2 wild-type and the variants of concern, including variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Our approach was based on extensive molecular docking, assessment of drug-likeness, and robust molecular dynamics simulations. We also identified promising inhibitory candidates against the host (human) proteins associated with SARS-CoV-2 spike activation and attachment, namely, ACE2 receptor, proteases TMPRSS2 and CTSL, and the endocytic regulator AAK1. In addition, we screened promising inhibitory compounds against the human proinflammatory cytokines- IL-6, IL-1ß, TNF-α, and IFN-γ, that are associated with the adverse cytokine storm in COVID-19 patients. Our analysis returned an encouraging list of promising inhibitory candidates that includes: abietatriene against the spike proteins of the SARS-CoV-2 wild-type and the variants of concern; taraxerol against the human ACE2, CTSL and TNF-α; ß-amyrin against the human TMPRSS2; cynaroside against the human AAK1 and IL-1ß; and friedelin against the human IL-6 and IFN-γ. Our findings provide substantial evidence for the inhibitory potential of these compounds and encourage further in vitro and in vivo studies to validate their use as safe and effective therapeutics against COVID-19.

Anisotine and amarogentin as promising inhibitory candidates against SARS-CoV-2 proteins: a computational investigation.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an unprecedented challenge to global public health with researchers striving to find a possible therapeutic candidate that could limit the spread of the virus. In this context, the present study employed an in silico molecular interaction-based approach to estimate the inhibitory potential of the phytochemicals from ethnomedicinally relevant Indian plants including Justicia adhatoda, Ocimum sanctum and Swertia chirata, with reported antiviral activities against crucial SARS-CoV-2 proteins. SARS-CoV-2 proteins associated with host attachment and viral replication namely, spike protein, main protease enzyme Mpro and RNA-dependent RNA polymerase (RdRp) are promising druggable targets for COVID-19 therapeutic research. Extensive molecular docking of the phytocompounds at the binding pockets of the viral proteins revealed their promising inhibitory potential. Subsequent assessment of physicochemical features and potential toxicity of the compounds followed by robust molecular dynamics simulations and analysis of MM-PBSA energy scoring function revealed anisotine against SARS-CoV-2 spike and Mpro proteins and amarogentin against SARS-CoV-2 RdRp as potential inhibitors. It was interesting to note that these compounds displayed significantly higher binding energy scores against the respective SARS-CoV-2 proteins compared to the relevant drugs that are currently being targeted against them. Present research findings confer scopes to explore further the potential of these compounds in vitro and in vivo towards deployment as efficient SARS-CoV-2 inhibitors and development of novel effective therapeutics.Communicated by Ramaswamy H. Sarma.

Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, Mpro and PLpro of SARS-CoV-2: Protein-Protein Interactions, Dynamics Simulations and Free Energy Calculations.

The emergence of COVID-19 continues to pose severe threats to global public health. The pandemic has infected over 171 million people and claimed more than 3.5 million lives to date. We investigated the binding potential of antiviral cyanobacterial proteins including cyanovirin-N, scytovirin and phycocyanin with fundamental proteins involved in attachment and replication of SARS-CoV-2. Cyanovirin-N displayed the highest binding energy scores (-16.8 ± 0.02 kcal/mol, -12.3 ± 0.03 kcal/mol and -13.4 ± 0.02 kcal/mol, respectively) with the spike protein, the main protease (Mpro) and the papainlike protease (PLpro) of SARS-CoV-2. Cyanovirin-N was observed to interact with the crucial residues involved in the attachment of the human ACE2 receptor. Analysis of the binding affinities calculated employing the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) approach revealed that all forms of energy, except the polar solvation energy, favourably contributed to the interactions of cyanovirin-N with the viral proteins. With particular emphasis on cyanovirin-N, the current work presents evidence for the potential inhibition of SARS-CoV-2 by cyanobacterial proteins, and offers the opportunity for in vitro and in vivo experiments to deploy the cyanobacterial proteins as valuable therapeutics against COVID-19.

Natural compounds from Clerodendrum spp. as possible therapeutic candidates against SARS-CoV-2: An in silico investigation.

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has rattled global public health, with researchers struggling to find specific therapeutic solutions. In this context, the present study employed an in silico approach to assess the inhibitory potential of the phytochemicals obtained from GC-MS analysis of twelve Clerodendrum species against the imperative spike protein, main protease enzyme Mpro and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. An extensive molecular docking investigation of the phytocompounds at the active binding pockets of the viral proteins revealed promising inhibitory potential of the phytochemicals taraxerol, friedelin and stigmasterol. Decent physicochemical attributes of the compounds in accordance with Lipinski's rule of five and Veber's rule further established them as potential therapeutic candidates against SARS-CoV-2. Molecular mechanics-generalized Born surface area (MM-GBSA) binding free energy estimation revealed that taraxerol was the most promising candidate displaying the highest binding efficacy with all the concerned SARS-CoV-2 proteins included in the present analysis. Our observations were supported by robust molecular dynamics simulations of the complexes of the viral proteins with taraxerol for a timescale of 40 nanoseconds. It was striking to note that taraxerol exhibited better binding energy scores with the concerned viral proteins than the drugs that are specifically targeted against them. The present results promise to provide new avenues to further evaluate the potential of the phytocompound taraxerol in vitro and in vivo towards its successful deployment as a SARS-CoV-2 inhibitor and combat the catastrophic COVID-19.Communicated by Ramaswamy H. Sarma.

Cyanobacterial metabolites as promising drug leads against the Mpro and PLpro of SARS-CoV-2: an in silico analysis.

A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged as the causative agent behind the coronavirus disease 2019 (COVID-19) pandemic. Treatment efforts have been severely impeded due to the lack of specific effective antiviral drugs for the treatment of COVID-associated pathologies. In the present research endeavour the inhibitory prospects of cyanobacterial metabolites were assessed at the active binding pockets of the two vital SARS-CoV-2 proteases namely, main protease (Mpro) and the papain-like protease (PLpro) that proteolytically process viral polyproteins and facilitate viral replication, employing an in silico molecular interaction-based approach. It was evident from our analysis based on the binding energy scores that the metabolites cylindrospermopsin, deoxycylindrospermopsin, carrageenan, cryptophycin 52, eucapsitrione, tjipanazole, tolyporphin and apratoxin A exhibited promising inhibitory potential against the SARS-CoV-2 Mpro. The compounds cryptophycin 1, cryptophycin 52 and deoxycylindrospermopsin were observed to display encouraging binding energy scores with the PLpro of SARS-CoV-2. Subsequent estimation of physicochemical properties and potential toxicity of the metabolites followed by robust molecular dynamics simulations and analysis of MM-PBSA energy scoring function established deoxycylindrospermopsin as the most promising inhibitory candidate against both SARS-CoV-2 proteases. Present research findings bestow ample scopes to further exploit the potential of deoxycylindrospermopsin as a successful inhibitor of SARS-CoV-2 in vitro and in vivo and pave the foundation for the development of novel effective therapeutics against COVID-19.Communicated by Ramaswamy H. Sarma.

The antioxidant rich active principles of Clerodendrum sp. controls haloalkane xenobiotic induced hepatic damage in murine model.

Clerodendrum is a plant with potent antioxidant activity and has been frequently employed as a traditional remedy against bronchitis, asthma, liver and stomach disorders. Three species of genus Clerodendrum namely Clerodendrum indicum, C. colebrookianum and C. inerme (Syn. Volkameria inermis) were investigated for their possible activity against oxidative stress induced liver injury. Apart from generation of Reactive Oxygen Species (ROS) in the WRL-68 cell line (human hepatic cell line), in-vitro and in-vivo antioxidant assays were also assessed. Features of immune cell proliferation (MTT) were analyzed thoroughly. Gas Chromatography-Mass Spectrometry (GC-MS) and Fourier Transform Infrared Spectroscopy (FTIR) analyses have been performed to identify the active biological compounds. These active biological compounds were further subjected to molecular docking. The antioxidant activity of three Clerodendrum sp. was significantly high in DPPH, nitric oxide, hydroxyl radical and hydrogen peroxide etc. Biochemical parameters like catalase, superoxide dismutase (SOD) and reduced glutathione (GSH) were generated in excess due to CCl4 administration, which was ameliorated by treating with Clerodendrum extract. The phytochemical 24,25-Dihydroxyvitamin D shows excellent binding affinity in Autodock Vina. The present study provided convincing evidences that C. indicum and C. inerme showed good result but C. colebrookianum performed better by almost all means.

Amelioration of CCl4 induced liver injury in swiss albino mice by antioxidant rich leaf extract of Croton bonplandianus Baill.

The progress in industrialization has blessed mankind with a technologically superior lifestyle but poor management of industrial waste has in turn poisoned nature. One such chemical is carbon tetra chloride (CCl4), which is a potent environmental toxin emitted from chemical industries and its presence in the atmosphere is increasing at an alarming rate. Presence of CCl4 in human body is reported to cause liver damage through free radical mediated inflammatory processes. Kupffer cells present in the liver are potentially more sensitive to oxidative stress than hepatocytes. Kuffer cells produced tumor necrosis factor-α (TNF-α) in response to reactive oxygen species (ROS), that might further cause inflammation or apoptosis. In this study hepatoprotective capacity of antioxidant rich extract of Croton bonplandianus Baill. (CBL) was evaluated on CCl4 induced acute hepatotoxicity in murine model. Hydro-methanolic extract of C. bonplandianus leaf was used for evaluation of free radical scavenging activity. Liver cells of experimental mice were damaged using CCl4 and subsequently hepatoprotective potential of the plant extract was evaluated using series of in-vivo and in-vitro studies. In the hepatoprotective study, silymarin was used as a positive control. Antioxidant enzymes, pro-inflammatory markers, liver enzymatic and biochemical parameters were studied to evaluate hepatoprotective activity of Croton bonplandianus leaf extract. Free radical scavenging activity of CBL extract was also observed in WRL-68 cell line. The phytochemicals identified by GCMS analysis were scrutinized using in-silico molecular docking procedure. The results showed that CBL extract have potent free radical scavenging capacity. The biochemical parameters were over expressed due to CCl4 administration, which were significantly normalized by CBL extract treatment. This finding was also supported by histopathological evidences showing less hepatocellularnecrosis, inflammation and fibrosis in CBL and silymarin treated group, compared to CCl4 group. ROS generated due to H2O2 in WRL-68 cell line were normalize in the highest group (200 µg/ml) when compared with control and negative control (CCl4) group. After molecular docking analysis, it was observed that the compound α-amyrin present in the leaf extract of C. bonplandianus has better potentiality to protect hepatocellular damages than the standard drug Silymarin. The present study provided supportive evidence that CBL extract possesses potent hepatoprotective capacity by ameliorating haloalkane induced liver injury in the murine model. The antioxidant and anti-inflammatory activities also affirm the same. The synergistic effects of the phytochemicals present in CBL are to be credited for all the hepatoprotective activity claimed above.

Permanent Draft Genome Sequence of the French Bean Symbiont Rhizobium sp. Strain RSm-3 Isolated from the Eastern Himalayan Region of India.

The genus Rhizobium contains many species able to form nitrogen-fixing nodules on plants of the legume family. Here, we report the 6.9-Mbp draft genome sequence of Rhizobium sp. strain RSm-3, with a G+C content of 61.4% and 6,511 candidate protein-coding genes.

Ethnobotany, traditional knowledge and socioeconomic importance of native drink among the Oraon tribe of Malda district in India.

AIM: Preparation of daily traditional drink by the indigenous tribes is a common phenomenon in India. Oraon tribes in Malda district of West Bengal, India are very much practiced in making of their own native brew, known as Chullu. Therefore, the aim of this study was to explore the whole Chullu procedure technology of the region and its socioeconomic effect on Oraon. Ethnomedicinal investigation of local plants involved in Chullu preparation was another aspect of this study. MATERIALS AND METHODS: The present study was conducted from April 2012 to June 2013. Consecutive field surveys were performed to collect information from Chullu producers to focus the procedure technology of local brew by means of semi-structured individual interviews, informal interviews and group discussion. A semi-structured questionnaire process was also performed to obtain the information regarding the ethnic use of plant species involved in Chullu preparation. RESULTS: The present study revealed that four medicinal plant species along with rice having strong local ethnomedicinal value were used to prepare this indigenous drink. Oraon prepare the brew using their unique home-made distillation process. Commercialization of this local brew represents an alternative income to develop their economic condition, especially for poor households. The index of importance value was considered to evaluate the importance, usage, and knowledge of the five studied species. CONCLUSION: It could be concluded that practices of Chullu preparation represent a bonding between ethnic knowledge and Oraon people of the province. Commercialization of Chullu may be considered as a source of alternative way of income for poor households in the region.

Indigenous knowledge of plants in local healthcare management practices by tribal people of Malda district, India.

AIM: The present study was aimed at exploring the indigenous knowledge of native tribes on the utilization of wild plant species for local healthcare management in Malda district of West Bengal. MATERIALS AND METHODS: Successive field surveys were carried out from July 2012 to August 2013 in search of traditional healers or practitioners who ceaselessly use their worthy knowledge to treat several ailments for human purposes. The information was collected by means of open-ended conversations, semi-structured questionnaire, group discussion, etc. Information obtained from the informants was also cross verified to check the authenticity. RESULTS: The present study revealed that a total of 53 medicinal plants belonging to the 37 families are frequently used to treat 44 types of ailments with 88 herbal preparations. Of 53 plants, herbs possess the highest growth forms (32%) that were used in making traditional preparation, followed by shrubs (24%), trees (23%), climbers (17%), and parasites (4%). Roots comprised the major plant parts used (25%), followed by leaves (21%), seeds (17%), bark (13%), whole plant (8%) and fruits (6%) to prepare the medicinal formulations. The chief ailments treated in this province were azoospermia, diabetes, menstrual disorder, dysentery, rheumatism, etc. CONCLUSION: It can be concluded that the documentation of the ethnobotanical knowledge in management of local healthcare is the first step, which will open new door for the researchers in the field of modern drug development.

Evaluation of phytochemical constituents and antioxidant activity of selected actinorhizal fruits growing in the forests of Northeast India.

Hippophae salicifolia, Elaeagnus pyriformis, Myrica esculenta and M. nagi are actinorhizal plants growing in the sacred forests of Northeast India with multipurpose uses. The present investigation was undertaken to determine the phenol, flavonoid and flavonol contents of the fresh fruit juice of these plant species including the antioxidant potential by means of DPPH, H2O2 and NO scavenging activity and FRP. The total phenolic, flavonoid and flavonol contents of fruit juice ranged from 321.68+/-0.06 to 76.67+/-0.01 mg/g GAE, 272.92+/-0.07 to 20.12+/-0.02 mg/g QE and 258.92+/-0.08 to 18.72+/-0.02 mg/g QE, respectively. At 2.0 mg/mL concentration, DPPH scavenging activity was found to be the highest in M. esculenta (89.62 percent) and the lowest in E. pyriformis (17.58 percent). The reducing power activity was found significantly higher in H. salicifolia juice, which increased with increase in concentration. The H2O2 scavenging activity of H. salicifolia juice was found to be as high as 98.78 percent, while Elaeagnus juice was found to be less effective with just 48.90 percent. Juice of H. salicifolia showed the greatest NO scavenging effect of 75.24 percent as compared to juice of E. pyriformis, where only 37.54 percent scavenging was observed at the same concentration. Taking into account all the experimental data, it can be said that the fruits of H. salicifolia and both M. nagi and M. esculenta have good antioxidant activity compared to fruits of E. pyriformis.