The growth responses of nine human intestinal bacteria to liquid culture of Cordyceps militaris Link. Pt. (Ascomycotina: Clavicipitaceae) collected from a pupa of Bombyx mori L. (Lepidoptera: Bombycidae) were examined using spectrophotometric and impregnated paper disk methods and compared to those of tetracycline and chloramphenicol, as well as those of Coptis japonica root-derived berberine chloride. The biologically active constituent of the cultures was characterized as cordycepin (3'-deoxyadenosine) by spectroscopic analysis. This compound revealed potent growth-inhibiting activity toward Clostridium paraputrificum and Clostridium perfringens at 10 microgram/disk without adverse effects on the growth of Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium adolescentis, Lactobacillus acidophilus, and Lactobacillus casei, whereas tetracycline and chloramphenicol inhibited the growth of these lactic acid-producing bacteria, clostridia and Escherichia coli. However, C. militaris-derived materials revealed no growth stimulation on the bifidobacteria and lactobacilli. These results may be an indication of at least one of the pharmacological actions of C. militaris. As a naturally occurring antibacterial agent, cordycepin could be useful as a new preventive agent against various diseases caused by clostridia.
We investigated the roles and biochemical properties of recombinant murine norovirus-1 (MNV-1) 3D pol in RNA synthesis and virus genome-linked protein (VPg) nucleotidylylation. We therefore was the probable target site of guanylylation. Homopolymeric RNAs did not enhance VPg guanylylation, whereas in vitro-transcribed (") subgenomic (SG) and (+)SG RNA enhanced VPg guanylylation by 9.2 and 3.2 times, respectively. Within (")SG RNA, the (")ORF3 region played a critical role in enhancing VPg guanylylation, suggesting that the MNV-1 ORF3 region of negativestrand RNA contains a cis-acting element that stimulates 3D pol -mediated VPg guanylylation.
Norovirus is one of the leading agents of gastroenteritis and is a major public health concern. In this study, the crystal structures of recombinant RNA-dependent RNA polymerase (RdRp) from murine norovirus-1 (MNV-1) and its complex with 5-fluorouracil (5FU) were determined at 2.5 Å resolution. Crystals with C2 symmetry revealed a dimer with half a dimer in the asymmetrical unit, and the protein exists predominantly as a monomer in solution, in equilibrium with a smaller population of dimers, trimers and hexamers. MNV-1 RdRp exhibited polymerization activity with a right-hand fold typical of polynucleotide polymerases. The metal ion modelled in close proximity to the active site was found to be coordinated tetrahedrally to the carboxyl groups of aspartate clusters. The orientation of 5FU observed in three molecules in the asymmetrical unit was found to be slightly different, but it was stabilized by a network of favourable interactions with the conserved active-site residues Arg185, Asp245, Asp346, Asp347 and Arg395. The information gained on the structural and functional features of MNV-1 RdRp will be helpful in understanding replication of norovirus and in designing novel therapeutic agents against this important pathogen.
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