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Molecular diagnosis and surveillance of pathogens such as SARS‐CoV‐2 depend on nucleic acid isolation. Pandemics at the scale of COVID‐19 can cause a global shortage of proprietary commercial reagents and BSL‐2 laboratories to safely perform testing. Therefore, alternative solutions are urgently needed to address these challenges. An open‐source method, magnetic‐nanoparticle‐aided viral RNA isolation from contagious samples (MAVRICS), built upon readily available reagents, and easily assembled in any basically equipped laboratory, is thus developed. The performance of MAVRICS is evaluated using validated pathogen detection assays and real‐world and contrived samples. Unlike conventional methods, MAVRICS works directly in samples inactivated in phenol‐chloroform (e.g., TRIzol), thus allowing infectious samples to be handled safely without biocontainment facilities. MAVRICS allows wastewater biomass immobilized on membranes to be directly inactivated and lysed in TRIzol followed by RNA extraction by magnetic nanoparticles, thereby greatly reducing biohazard risk and simplifying processing procedures. Using 39 COVID‐19 patient samples and two wastewater samples, it is shown that MAVRICS rivals commercial kits in detection of SARS‐CoV‐2, influenza viruses, and respiratory syncytial virus. Therefore, MAVRICS is safe, fast, and scalable. It is field‐deployable with minimal equipment requirements and could become an enabling technology for widespread testing and wastewater monitoring of diverse pathogens. [ABSTRACT FROM AUTHOR]

A reagent‐directed divergent synthesis of three skeletally distinct compounds, namely, amino‐substituted indolizidine alkaloids, decahydropyrazino[2,1,6‐cd]‐pyrrolizine triols and (–)‐pochonicine stereoisomers have been accomplished from a single precursor. Tri‐O‐benzyl‐d‐glucal was converted into a diastereomeric mixture of homoallylic alcohols through a seven‐step sequence developed earlier in our lab. Intramolecular iodo‐amination of the homoallylic alcohols proceeded through a 5‐exo‐tet ring opening of initially formed iodonium ion to give the iodo‐substituted pyrrolizidine {[5,5‐]‐fused} derivatives. Upon exposure to AgOAc, these iodo‐pyrrolizidines underwent a ring enlargement under the reaction condition and delivered polyhydroxylated indolizidine {[5,6]‐fused} derivatives as the main products. On the other hand, when the iodo‐pyrrolizidines were treated with NaH, a smooth intramolecular substitution reaction took place resulting in the formation of novel decahydropyrazino[2,1,6‐cd]pyrrolizine triols in good yields. Diversely, epoxidation of the homoallyic alcohols followed by intramolecular ring opening and subsequent synthetic transformations delivered stereoisomers of (–)‐pochonicine. The structure and stereochemistry of the final compounds were established through detailed 2D‐NMR analysis. [ABSTRACT FROM AUTHOR]

The mitochondrial F-type ATP synthase, a multisubunit nanomotor, is critical for maintaining cellular ATP levels. In T. gondii and other apicomplexan parasites, many subunit components necessary for proper assembly and functioning of this enzyme appear to be missing. Here, we report the identification of 20 novel subunits of T. gondii F-type ATP synthase from mass spectrometry analysis of partially purified monomeric (approximately 600 kDa) and dimeric (>1 MDa) forms of the enzyme. Despite extreme sequence diversification, key FO subunits a, b, and d can be identified from conserved structural features. Orthologs for these proteins are restricted to apicomplexan, chromerid, and dinoflagellate species. Interestingly, their absence in ciliates indicates a major diversion, with respect to subunit composition of this enzyme, within the alveolate clade. Discovery of these highly diversified novel components of the apicomplexan F-type ATP synthase complex could facilitate the development of novel antiparasitic agents. Structural and functional characterization of this unusual enzyme complex will advance our fundamental understanding of energy metabolism in apicomplexan species. [ABSTRACT FROM AUTHOR]

Electrodeposition of gold nanoparticles (Au-NPs) decorated single polypyrrole nanowire (Ppy-NW) for arsenic (As) detection was studied in this paper. Arsenic is a toxic element, which exists in variety of chemical forms. Arsenic forms combined with groundwater and soil is leading to toxicity and creating health risks, hence the requirement of its detection arises. The present study is to develop a highly sensitive Au-NPs decorated Ppy-NW based sensor for detecting the trace amounts of arsenic (As). The chemiresistive method was adopted for detecting the sensitivity of the arsenic traces. A 200 nm in diameter Ppy nanowires were developed using anodic aluminum oxide (AAO) template based synthesis and decorated with Au-NPs and further tested for arsenic sensing. The response of arsenic with the sensors was recorded by chemiresistive method with varying potential between ±100 mV. The sensitivity of Au-NPs decorated Ppy-NW towards arsenic (for two set of As conc. range) was observed to be 0.22 and 4.38 µM and the detection limit of the sensor was observed to be 0.32 µM [ABSTRACT FROM AUTHOR]

A concise total synthesis of the four stereoisomers of (-)-pochonicine was undertaken. The key steps of the synthesis involved chemoselective debenzylation of the primary benzyloxy group and an unprecedented Na-Hg-mediated concomitant N-detosylative intramolecular epoxide ring-opening reaction. Notably, additional steps for the protection of other functional groups were not required. Glycosidase inhibition studies revealed that these compounds are inhibitors of β- N-acetylglucosaminidase with IC50 values in the sub-millimolar range. [ABSTRACT FROM AUTHOR]

A series of novel 3- methyl-7-substituted-4H-1,4-benzothiazine-2- carbohydrazide (3a-e) and corresponding thiosemicarbazides (4-a-q); 2-[3-methyl-7- substituted- 4H -1, 4-benzothiazine-2-yl]-N-(aryl) hydrazine carbothiamide have been synthesized. The thiosemicarbazide when cyclized with iodine via intramolecular cyclisation gave benzothiazonyl oxadiazoles (5-a-q); 5-(3-methyl -7-substitued-4H- 1,4-benzothiazin-2-yl)- N -aryl- 1,3,4- oxadiazol -2-amine and the compounds were tested for antibacterial and antifungal activities against different microorganisms. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Highly diverged novel subunit composition of apicomplexan F-type ATP synthase identified from Toxoplasma gondii" which appeared in the July 13, 2018 issue.

• RT-LAMP coupled with CRISPR-Cas12 provides a sensitive and specific virus detection platform. • iSCAN sensitivity and specificity are comparable with RT-qPCR. • iSCAN is a 1 h detection module that can help in testing in low resource areas. • iSCAN can be developed as a one-pot assay. • iSCAN reagents can be produced locally and deployed for SARS-CoV2 detection. The COVID-19 pandemic caused by SARS-CoV-2 affects all aspects of human life. Detection platforms that are efficient, rapid, accurate, specific, sensitive, and user friendly are urgently needed to manage and control the spread of SARS-CoV-2. RT-qPCR based methods are the gold standard for SARS-CoV-2 detection. However, these methods require trained personnel, sophisticated infrastructure, and a long turnaround time, thereby limiting their usefulness. Reverse transcription-loop-mediated isothermal amplification (RT-LAMP), a one-step nucleic acid amplification method conducted at a single temperature, has been used for colorimetric virus detection. CRISPR-Cas12 and CRISPR-Cas13 systems, which possess collateral activity against ssDNA and RNA, respectively, have also been harnessed for virus detection. Here, we built an efficient, rapid, specific, sensitive, user-friendly SARS-CoV-2 detection module that combines the robust virus amplification of RT-LAMP with the specific detection ability of SARS-CoV-2 by CRISPR-Cas12. Furthermore, we combined the RT-LAMP-CRISPR-Cas12 module with lateral flow cells to enable highly efficient point-of-care SARS-CoV-2 detection. Our iSCAN SARS-CoV-2 detection module, which exhibits the critical features of a robust molecular diagnostic device, should facilitate the effective management and control of COVID-19. [ABSTRACT FROM AUTHOR]

A novel protecting group directed diversity leading to the synthesis of bridged bicyclic and six-membered iminocyclitols from a common carbohydrate derived diamino triol under Mitsunobu conditions is reported. When the intramolecular cyclization of benzoyl derivative 16 was carried out under Mitsunobu conditions, an unprecedented one-pot domino intramolecular "cyclization-N→O benzoyl migration-cyclization" reaction sequence occurred resulting in the formation of a chiral 2,6-diazabicyclo[3.2.1]octane-4,8-diol 21 in high yield. The structure of this novel bridged bicyclic compound was established through detailed NMR studies and single crystal X-ray analysis. On the other hand, the tert-butyldimethylsilyl derivative of the same substrate afforded protected 6-amino-1,6-dideoxy-l-gulonojirimycin 32 as the sole product under identical conditions. An attempt has been made to explain this difference in their reactivity through conformational analysis. The glycosidase inhibition studies of new compounds reported in this manuscript revealed that these molecules display moderate but selective inhibition against β-N-acetylhexosaminidase.

Using the intramolecular 5-exo-5-hexenyl radical as a key cyclization step, we previously reported an unambiguous synthesis of carba-LNA thymine (cLNA-T), which we subsequently incorporated in antisense oligonucleotides (AON) and investigated their biochemical properties [J. Am. Chem. Soc.2007, 129 (26), 8362-8379]. These cLNA-T incorporated oligos showed specific RNA affinity of +3.5-5 °C/modification for AON:RNA heteroduplexes, which is comparable to what is found for those of LNAs (Locked Nucleic Acids). These modified oligos however showed significantly enhanced nuclease stability (ca. 100 times more) in the blood serum compared to those of the LNA modified counterparts without compromising any RNase H recruitment capability. We herein report the synthesis of 5-methylcytosine-1-yl ((Me)C), 9-adeninyl (A), and 9-guaninyl (G) derivatives of cLNA and their oligonucleotides and report their biochemical properties as potential RNA-directed inhibitors. In a series of isosequential carba-LNA modified AONs, we herein show that all the cLNA modified AONs are found to be RNA-selective, but the magnitude of RNA-selectivity of 7'-R-Me-cLNA-G (cLNA-G) (ΔT(m) = 2.9 °C/modification) and intractable isomeric mixtures of 7'-(S/R)-Me-cLNA-T (cLNA-T, ΔT(m) = 2.2 °C/modification) was found to be better than diastereomeric mixtures of 7'-(S/R)-Me-cLNA-(Me)C with trace of cENA-(Me)C (cLNA-(Me)C, ΔT(m) = 1.8 °C/modification) and 7'-R-Me-cLNA-A (cLNA-A, ΔT(m) = 0.9 °C/modification). cLNA-(Me)C modified AONs however exhibited the best nuclease stability, which is 4-, 7-, and 20-fold better, respectively, than cLNA-T, cLNA-A, and cLNA-G modified counterparts, which in turn was more than 100 times stable than that of the native. When the modification sites are appropriately chosen in the AONs, the cLNA-A, -G, and -(Me)C modified sites in the AON:RNA hybrids can be easily recognized by RNase H, and the RNA strand of the hybrid is degraded in a specific manner, which is important for the design of oligos for therapeutic purposes. The cLNA-(Me)C modified AON/RNA, however, has been found to be degraded 4 times faster than cLNA-A and G modified counterparts. By appropriately choosing the carba-LNA modification sites in AON strands, the digestion of AON:RNA can be either totally repressed or be limited to cleavage at specific sites or at a single site only (similar to that of catalytic RNAzyme or DNAzyme). Considering all physico- and biochemical aspects of cLNA modified oligos, the work suggests that the cLNA modified antisense oligos have the potential of being a promising therapeutic candidate due to their (i) higher nucleobase-specific RNA affinity and RNA selectivity, (ii) greatly improved nuclease stability, and (iii) efficient RNase H recruitment capability, which can induce target RNA cleavage in a very specific manner at multiple or at a single site, in a designed manner.