01594nas a2200193   4500008004100000245013500041210006900176260000800245300001400253490000700267520084500274100001901119700002201138700002001160700003101180700003701211700002401248856012801272       2013                        eng d00aSelf-assembly to function: design, synthesis and broad spectrum antimicrobial properties of short hybrid E-vinylogous lipopeptides0 aSelfassembly to function design synthesis and broad spectrum ant  cNOV  a8468-84740 v563 aNonribosomal E-vinylogous gamma-amino acids are widely present in many peptide natural products and have been exploited as inhibitors for serine and cysteine proteases. Here, we are reporting the broad spectrum antimicrobial properties and self-assembled nanostructures of various hybrid lipopeptides composed of 1:1 alternating alpha-and E-vinylogous residues. Analysis of the results revealed that self-assembled nanostructures also play a significant role in the antimicrobial and hemolytic activities. In contrast to the alpha-peptide counterparts, vinylogous hybrid peptides displayed excellent antimicrobial properties against various bacterial and fungal strains. Peptides that adopted nanofiber structures displayed less hemolytic activity, while peptides that adopted nanoneedle structures displayed the highest hemolytic activity.1 aShankar, Shiva1 aBenke, Sushil, N.1 aNagendra, Narem1 aSrivastava, Prabhakar, Lal1 aThulasiram, Hirekodathakallu, V.1 aGopi, Hosahudya, N.  uhttp://library.ncl.res.in/content/self-assembly-function-design-synthesis-and-broad-spectrum-antimicrobial-properties-short02339nas a2200205   4500008004100000022001400041245010400055210006900159260009000228300002600318490000600344520149100350100003101841700002501872700002701897700002201924700001901946700003701965856013102002       2015                        eng d  a2045-232200aFunctional characterization of novel sesquiterpene synthases from Indian sandalwood, santalum album0 aFunctional characterization of novel sesquiterpene synthases fro  aMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLANDbNATURE PUBLISHING GROUPcMAY  aArticle Number: 100950 v53 a<p>Indian Sandalwood, Santalum album L. is highly valued for its fragrant heartwood oil and is dominated by a blend of sesquiterpenes. Sesquiterpenes are formed through cyclization of farnesyl diphosphate (FPP), catalyzed by metal dependent terpene cyclases. This report describes the cloning and functional characterization of five genes, which encode two sesquisabinene synthases (SaSQS1, SaSQS2), bisabolene synthase (SaBS), santalene synthase (SaSS) and farnesyl diphosphate synthase (SaFDS) using the transcriptome sequencing of S. album. Using Illumina next generation sequencing, 33.32 million high quality raw reads were generated, which were assembled into 84,094 unigenes with an average length of 494.17 bp. Based on the transcriptome sequencing, five sesquiterpene synthases SaFDS, SaSQS1, SaSQS2, SaBS and SaSS involved in the biosynthesis of FPP, sesquisabinene, beta-bisabolene and santalenes, respectively, were cloned and functionally characterized. Novel sesquiterpene synthases (SaSQS1 and SaSQS2) were characterized as isoforms of sesquisabinene synthase with varying kinetic parameters and expression levels. Furthermore, the feasibility of microbial production of sesquisabinene from both the unigenes, SaSQS1 and SaSQS2 in non-optimized bacterial cell for the preparative scale production of sesquisabinene has been demonstrated. These results may pave the way for in vivo production of sandalwood sesquiterpenes in genetically tractable heterologous systems.</p>1 aSrivastava, Prabhakar, Lal1 aDaramwar, Pankaj, P.1 aKrithika, Ramakrishnan1 aPandreka, Avinash1 aShankar, Shiva1 aThulasiram, Hirekodathakallu, V.  uhttp://library.ncl.res.in/content/functional-characterization-novel-sesquiterpene-synthases-indian-sandalwood-santalum-album-102931nas a2200313   4500008004100000022001400041245013200055210006900187260000800256520189100264653001602155653001302171653001102184653000902195653003302204653002302237653000902260653002102269100002202290700002502312700002302337700001902360700002602379700002702405700001702432700002002449700002502469856012302494       2020                        eng d  a0739-110200aDiscovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease0 aDiscovery of potential multitargetdirected ligands by targeting   cMAY3 a<p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected over 2.5 million individuals with a mortality rate ranging from 5 to 10%. There are several efforts going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (M-Pro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of M-Pro, we have performed phylogenetic and Sequence Similarity Network analysis, that depicted divergence of Coronaviridae M-Pro in five clusters specific to viral hosts. This clustering was corroborated with the comparison of M-Pro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. These attributes can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 M-Pro. In agreement with this, we performed screening of similar to 7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 M-Pro as the primary target. We identified several natural molecules like delta-viniferin, myricitrin, taiwanhomoflavone A, lactucopicrin 15-oxalate, nympholide A, afzelin, biorobin, hesperidin and phyllaemblicin B that strongly binds to SARS-CoV-2 M-Pro. Intrestingly, these molecules also showed strong binding with other potential targets of SARS-CoV-2 infection like viral receptor human angiotensin-converting enzyme 2 (hACE-2) and RNA dependent RNA polymerase (RdRp). We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection. Communicated by Ramaswamy H. Sarma</p>
10aCoronavirus10aCOVID-1910ahACE-210aMPro10amulti-target-directed ligand10aprotease inhibitor10aRdRp10aSARS-CoV-2 virus1 aJoshi, Rakesh, S.1 aJagdale, Shounak, S.1 aBansode, Sneha, B.1 aShankar, Shiva1 aTellis, Meenakshi, B.1 aPandya, Vaibhav, Kumar1 aChugh, Anita1 aGiri, Ashok, P.1 aKulkarni, Mahesh, J.  uhttp://library.ncl.res.in/content/discovery-potential-multi-target-directed-ligands-targeting-host-specific-sars-cov-2