Recent Advances in Tetrazole Derivatives as Potential Antiviral Agents

Viruses use the host cell’s biochemical machinery for replication and survival; and also undergo mutations to evade the immune response and achieve better transmission. These features make it challenging to develop selective drugs to kill viruses only and not the host cells. New and effective pharmaceutical agents are required to overcome this challenge. Tetrazole moiety, as a bio-isostere of carboxylic acid/amide group, has been extensively used as a potent pharmacophore in several bioactivities. Intrigued by the necessity of finding new antiviral compounds and tendency of tetrazole scaffolds to render various bioactivity profiles, this review article comprising literature reports of tetrazole-based synthetic compounds with promising antiviral activity is presented. This review comprises significant literature reports from the scientific databases published during the past four decades. It is found that tetrazole based molecules are promising endeavor for the development of potential agents against influenza virus, HIV, HCV and other viruses.

Fungicide efficacy against Pseudoperonospora humuli and point-mutations linked to carboxylic acid amide (CAA) resistance in Michigan.

Hops have expanded as a niche crop in Michigan and other production areas in the eastern United States, but growers in these regions face annual downy mildew outbreaks incited by Pseudoperonospora humuli, exacerbated by frequent rainfall and high relative humidity. We evaluated the efficacy of foliar- and drench-applied fungicides against downy mildew and examined Michigan isolates for point mutations linked to carboxylic acid amide (CAA) resistance. Disease severity and density were assessed weekly in 2016 and 2017 in non-trellised research hop yards in Michigan. Area under the disease progress curve values for disease severity were significantly lower for plants treated with oxathiapiprolin, ametoctradin/dimethomorph, fluopicolide, cyazofamid, or mandipropamid (90.6 to 100% control) compared to those treated with fosetyl-Al (64.3 to 93.0% control) at both locations for both years. Drench treatments of fluopicolide and oxathiapiprolin/ mefenoxam reduced disease density and severity at both locations but were only moderately effective (76.4 to 91.5% control). To assess CAA resistance, the CesA3 gene was aligned using reference downy mildew species and primers designed to amplify the 1105 and 1109 amino acids. Point mutations conferring CAA resistance were not detected at these loci for sporangia from 42 symptomatic shoots collected from 11 commercial hop yards. These efficacy results for hop downy mildew are needed to guide disease recommendations in this expanding Michigan industry. The absence resistant genotypes indicate that Michigan growers can continue to utilize CAA-containing commercial fungicides as part of an overall downy mildew management program.

Detection and Characterization of Carboxylic Acid Amide-Resistant Plasmopara viticola in China Using a TaqMan-MGB Real-Time PCR

Grape production is increasing globally and so are problems with downy mildew, one of the main constraints in grape production. Downy mildew on grape is caused by Plasmopara viticola, an obligate biotrophic pathogen belonging to the oomycetes. Control of the disease is usually performed by fungicide applications, of which carboxylic acid amide (CAA) fungicides represent one of the most widely used groups of fungicides. Our previous research showed that the extensive application of CAA fungicides can result in fungicide resistance and in China, CAA-resistant isolates of P. viticola were collected from the field in 2014. To monitor the distribution and spread of CAA fungicide resistance, we developed a TaqMan-minor groove binder (MGB) real-time PCR-based method designed on a functional mutation in the PvCesA3 gene that allows efficient identification of CAA fungicide resistant and sensitive genotypes. The assay was validated on 50 isolates using Sanger sequencing and fungicide bioassays and exploited in a comprehensive survey comprising 2,227 single-sporangiophore isolates from eight major grapevine regions in China. We demonstrate that CAA fungicide resistance in P. viticola is widespread in China. On average, 53.3% of the isolates were found to be resistant, but marked differences were found between locations with percentages of resistant isolates varying from 0.3 to 96.6%. Furthermore, the frequency of CAA-resistant isolates was found to be significantly correlated with the exposure to CAA fungicides (P < 0.05). We further discussed the possibilities to apply the TaqMan-MGB real-time PCR assay to assess the frequency of fungicide-resistant P. viticola isolates in each region or vineyard, which would facilitate the correct choice of fungicide for grape downy mildew and resistance management strategies.

Crystal structures of three halide salts of L-asparagine: an isostructural series

The structures of three monohydrated halide salt forms of L-asparagine are presented, viz.L-asparaginium chloride monohydrate, C4H9N2O3 +·Cl−·H2O, (I), L-asparaginium bromide monohydrate, C4H9N2O3 +·Br−·H2O, (II), and L-asparaginium iodide monohydrate, C4H9N2O3 +·I−·H2O, (III). These form an isomorphous and isostructural series. The C—C—C—C backbone of the amino acid adopts a gauche conformation in each case [torsion angles for (I), (II) and (III) = −55.4 (2), −55.6 (5) and −58.3 (7)°, respectively]. Each cation features an intramolecular N—H...O hydrogen bond, which closes an S(6) ring. The extended structures feature chains of cations that propagate parallel to the b-axis direction. These are formed by carboxylic acid/amide complimentary O—H...O + N—H...O hydrogen bonds, which generate R 2 2(8) loops. These chains are linked by further hydrogen bonds mediated by the halide ions and water molecules to give a layered structure with cation and anion layers parallel to the ab plane. Compound (III) was refined as an inversion twin.

First Report of Carboxylic Acid Amide Fungicide Resistance in Plasmopara viticola (Grapevine Downy Mildew) in North America

This report documents the first known occurrence in North America of resistance in grape downy mildew (Plasmopara viticola) to the carboxylic acid amide (CAA) fungicides mandipropamid and dimethomorph. These fungicides (FRAC group 40) have been an important component of downy mildew management programs for the past decade. Resistant isolates were obtained at three locations in Virginia and one in North Carolina, at considerable distances from each other. Resistance was documented by bioassay and the presence of the G1105S mutation, which has been associated with CAA resistance of P. viticola in other areas. Further survey is needed to determine the geographic extent of this resistance.