A benzimidazole scaffold as a promising inhibitor against SARS-CoV-2.

The manuscript reports the green-chemical synthesis of a new diindole-substituted benzimidazole compound, B1 through a straightforward route in coupling between indolyl-3-carboxaldehyde and o-phenylenediamine in water medium under the aerobic condition at 75 ºC. The single crystal X-ray structural analysis of B1 suggests that the disubstituted benzimidazole compound crystallizes in a monoclinic system and the indole groups exist in a perpendicular fashion with respect to benzimidazole moiety. The SARS-CoV-2 screening activity has been studied against 1 × 10e4 VeroE6 cells in a dose-dependent manner following Hoechst 33342 and nucleocapsid staining activity with respect to remdesivir. The compound exhibits 92.4% cell viability for 30 h and 35.1% inhibition against VeroE6 cells at non-cytotoxic concentration. Molecular docking studies predict high binding propensities of B1 with the main protease (Mpro) and non-structural (nsp2 and nsp7-nsp8) proteins of SARS-CoV-2 through a number of non-covalent interactions. Molecular dynamics (MD) simulation analysis for 100 ns confirms the formation of stable conformations of B1-docked proteins with significant changes of binding energy, attributing the potential inhibition properties of the synthetic benzimidazole scaffold against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.

Transcriptome analysis of mulberry (Morus alba L.) leaves to identify differentially expressed genes associated with post-harvest shelf-life elongation.

Present study deals with molecular expression patterns responsible for post-harvest shelf-life extension of mulberry leaves. Quantitative profiling showed retention of primary metabolite and accumulation of stress markers in NS7 and CO7 respectively. The leaf mRNA profiles was sequenced using the Illumina platform to identify DEGs. A total of 3413 DEGs were identified between the treatments. Annotation with Arabidopsis database has identified 1022 DEGs unigenes. STRING generated protein-protein interaction, identified 1013 DEGs nodes with p < 1.0e-16. KEGG classifier has identified genes and their participating biological processes. MCODE and BiNGO detected sub-networking and ontological enrichment, respectively at p ≤ 0.05. Genes associated with chloroplast architecture, photosynthesis, detoxifying ROS and RCS, and innate-immune response were significantly up-regulated, responsible for extending shelf-life in NS7. Loss of storage sucrose, enhanced activity of senescence-related hormones, accumulation of xenobiotics, and development of osmotic stress inside tissue system was the probable reason for tissue deterioration in CO7. qPCR validation of DEGs was in good agreement with RNA sequencing results, indicating the reliability of the sequencing platform. Present outcome provides a molecular insight regarding involvement of genes in self-life extension, which might help the sericulture industry to overcome their pre-existing problems related to landless farmers and larval feeding during monsoon.

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.

In silico inquest reveals the efficacy of Cannabis in the treatment of post-Covid-19 related neurodegeneration.

Coronavirus (SARS-CoV-2), the causative agent of the Covid-19 pandemic has proved itself as the deadliest pathogen. A major portion of the population has become susceptible to this strain. Scientists are pushing their limits to formulate a vaccine against Covid-19 with the least side effects. Although the recent discoveries of vaccines have shown some relief from the covid infection rate, however, physical fatigue, mental abnormalities, inflammation and other multiple organ damages are arising as post-Covid symptoms. The long-term effects of these symptoms are massive. Patients with such symptoms are known as long-haulers and treatment strategy against this condition is still unknown. In this study, we tried to explore a strategy to deal with the post-Covid symptoms. We targeted three human proteins namely ACE2, Interleukin-6, Transmembrane serine protease and NRP1 which are already reported to be damaged via Covid-19 proteins and upregulated in the post-Covid stage. Our target plant in this study is Cannabis (popularly known as 'Ganja' in India). The molecular docking and simulation studies revealed that Cannabidiol (CBD) and Cannabivarin (CVN) obtained from Cannabis can bind to post-Covid symptoms related central nervous system (CNS) proteins and downregulate them which can be beneficial in post-covid symptoms treatment strategy. Thus we propose Cannabis as an important therapeutic plant against post-Covid symptoms.Communicated by Ramaswamy H. Sarma.

Encapsulated hydroxychloroquine and chloroquine into cyclic oligosaccharides are the potential therapeutics for COVID-19: insights from first-principles calculations.

Novel-Coronavirus (COVID-19) outburst has become a worldwide pandemic which threaten the scientific community to design and discover efficient and effective treatment strategies against this deadly virus (SARS-CoV-2). Still now, there is no antiviral therapy or drug available in the market which can efficiently combat the infection caused by this virus. In this respect, using available drugs by screening with molecular docking and molecular dynamics studies not only minimizes lengthy chemical trials but also reduces discovery cost for the pharmaceutical industry. During the COVID-19 pandemic situations hydroxychloroquine, chloroquine known as HCQ and CQ tablets have gained popularity as for the treatment coronavirus (COVID-19) but the main threatening effect of HCQ, CQ use lies on their side effects like blistering, peeling, loosening of the skin, blurred vision stomach pain, diarrhea, chest discomfort, pain, or tightness, cough or hoarseness which require immediate medical attention. Encapsulation of HCQ and CQ drugs by the cyclic macromolecules such as α and ß-Cyclodextrin, to form host-guest complexes is very effective strategy to mask the cytotoxicity of certain drugs and alleviating and modulating side effects of drug applications. In the present work, we have encapsulated the HCQ and CQ drugs α and ß-Cyclodextrin and made a comprehensive analysis of stability, optical properties. Details analysis verified that between QC and HCQ, HQC showed stronger affinity towards ß-Cyclodextrin. This strategy can reduce the side effect of HCQ and CQ thereby offers a new way to use these drugs. We hope the present study should help the researchers to develop potential therapeutics against the novel coronavirus.

A hydrated 2,3-diaminophenazinium chloride as a promising building block against SARS-CoV-2.

Phenazine scaffolds are the versatile secondary metabolites of bacterial origin. It functions in the biological control of plant pathogens and contributes to the producing strains ecological fitness and pathogenicity. In the light of the excellent therapeutic properties of phenazine, we have synthesized a hydrated 2,3-diaminophenazinium chloride (DAPH+Cl-·3H2O) through direct catalytic oxidation of o-phenylenediamine with an iron(III) complex, [Fe(1,10-phenanthroline)2Cl2]NO3 in ethanol under aerobic condition. The crystal structure, molecular complexity and supramolecular aspects of DAPH+Cl- were confirmed and elucidated with different spectroscopic methods and single crystal X-ray structural analysis. Crystal engineering study on DAPH+Cl- exhibits a fascinating formation of (H2O)2…Cl-…(H2O) cluster and energy framework analysis of defines the role of chloride ions in the stabilization of DAPH+Cl-. The bactericidal efficiency of the compound has been testified against few clinical bacteria like Streptococcus pneumoniae, Escherichia coli, K. pneumoniae using the disc diffusion method and the results of high inhibition zone suggest its excellent antibacterial properties. The phenazinium chloride exhibits a significant percentage of cell viability and a considerable inhibition property against SARS-CoV-2 at non-cytotoxic concentration compared to remdesivir. Molecular docking studies estimate a good binding propensity of DAPH+Cl- with non-structural proteins (nsp2 and nsp7-nsp-8) and the main protease (Mpro) of SARS-CoV-2. The molecular dynamics simulation studies attribute the conformationally stable structures of the DAPH+Cl- bound Mpro and nsp2, nsp7-nsp8 complexes as evident from the considerable binding energy values, - 19.2 ± 0.3, - 25.7 ± 0.1, and - 24.5 ± 0.7 kcal/mol, respectively.