Report of the Fifth Symposium on Emerging Viral Diseases

Emerging viral diseases pose global threat to public health. It is essential to build capacity to response and counteract against emerging viral diseases. Towards achieving this important goal of public health, the State Key Laboratory of Virology of China has organized the International Symposium on Emerging Viral

Stem cell therapy and diabetic erectile dysfunction:A critical review

Erectile dysfunction(ED)has been identified as one of the most frequent chronic complications of diabetes mellitus(DM).The prevalence of ED is estimated to be about 67.4%in all DM cases worldwide.The pathophysiological process leading to ED involves endothelial,neurological,hormonal,and psychological factors.In DM,endothelial and neurological factors play a crucial role.Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM.The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery.However,these treatments are limited in terms of just relieving the symptoms,but not resolving the cause of the problem.The use of stem cells for treating ED is currently being studied mostly in experimental animals.The stem cells used are derived from adipose tissue,bone,or human urine.Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue.However,research on stem cell therapy for ED in humans remains to be limited.Nevertheless,significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.

An Efficient Synthesis of Spiroquinoxalinones via Tandem Reactions

A mild and efficient synthesis of spiroquinoxalinones via tandem condensation of chlorooxoindoline 1 with benzene-1,2-diamines 2 is described.And a plausible mechanism for the reaction is proposed.

Flavivirus RNA cap methyltransferase:structure,function,and inhibition

Many flaviviruses are significant human pathogens.The plus-strand RNA genome of a flavivirus contains a 5′terminal cap 1 structure(m7GpppAmG).The flavivirus encodes one methyltransferase(MTase),located at the Nterminal portion of the NS5 RNA-dependent RNA polymerase(RdRp).Here we review recent advances in our understanding of flaviviral capping machinery and the implications for drug development.The NS5 MTase catalyzes both guanine N7 and ribose 2'-OH methylations during viral cap formation.Representative flavivirus MTases,from dengue,yellow fever,and West Nile virus(WNV),sequentially generate GpppA!m7GpppA!m7GpppAm.Despite the existence of two distinct methylation activities,the crystal structures of flavivirus MTases showed a single binding site for S-adenosyl-L-methionine(SAM),the methyl donor.This finding indicates that the substrate GpppA-RNA must be repositioned to accept the N7 and 2'-O methyl groups from SAM during the sequential reactions.Further studies demonstrated that distinct RNA elements are required for the methylations of guanine N7 on the cap and of ribose 2'-OH on the first transcribed nucleotide.Mutant enzymes with different methylation defects can trans complement one another in vitro,demonstrating that separate molecules of the enzyme can independently catalyze the two cap methylations in vitro.In the context of the infectious virus,defects in both methylations,or a defect in the N7 methylation alone,are lethal to WNV.However,viruses defective solely in 2'-O methylation are attenuated and can protect mice from later wild-typeWNV challenge.The results demonstrate that the N7 methylation activity is essential for the WNV life cycle and,thus,methyltransferase represents a novel and promising target for flavivirus therapy.