Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 18, Issue 2, 2018

Stereochemistry has occupied a great role in the manufacture and development of pharmaceuticals. Chiral properties play an important role in the determination of pharmacological actions of the drug. In recent years, there is a considerable interest in chiral separation to isolate and examine both enantiomers. This article provides an overview about the stereochemistry and its role in drugs, and also, offers approved isolation methods for enantiomeric pairs.

Ebola virus (EBOV) was discovered for the first time in 1976. It belongs to the family Filoviridae, which causes hemorrhagic fever that could lead to death in a few days. West Africa faced a major outbreak where symptoms appeared in the form of chills, myalgia, fever, diarrhea, and vomiting, and the disease finally reached a severe state as a result of hemorrhagic complications and failure of multiple organs. EBOV spreads by contact with body fluids of an infected person such as blood, saliva, urine, and seminal fluid, and also spreads by a contact with contaminated surfaces. Viral infection depends on the virus and host defenses. When the virus invades the body, the immune system becomes activated in an attempt to neutralize it. However, if this fails, EBOV viral infection spreads and leads to impaired innate and adaptive immune responses and uncontrollable viral replication. Consequently, the symptomatic patient is isolated and various medicinal regimens such as BCX-4430n TKM- EBOV are used, to cure EBOV, though, a specific treatment is not available. Accordingly, the aim of the present review is to survey and summarize the recent literature pertaining to the outbreak of EBOV, systematic infection of the human body, along with transmission and treatment. In addition, the review also aims to identify areas that need more research and development in combatting this dangerous virus. In the meantime, it should be noted that there is no fully FDA approved drug to treat infections by this virus. Therefore, there is a pressing need to focus on drug discovery along with public awareness to effectively manage any outbreaks in the future.

For many years, colchicine has been used for therapeutic purposes and has been given considerable attention because of its association with tubulin and inhibition of small tubular polymerization. Colchicine is an alkaloid extracted from the colchicum autumnale plant, having molecular formula C22H25NO6, and consists of three rings. Many studies are concerned with structural changes in order to increase their pharmacological effectiveness and reduce the side effects of toxicity arising from it. The therapeutic use of colchicine has been mainly documented in Gout, Familial Mediterranean Fever, and many other diseases such as atrial fibrillation. This review summarizes the history of chemical structure of colchicine and presents some of its analogues. Furthermore, it shows binding mechanism with target protein when colchicine is used as a therapeutic drug, and gives a light spot on some studies that discuss the safe use of colchicine.

Background & Aims: Cell-mediated immunity plays a critical role in viral clearance and disease progression during Hepatitis C virus (HCV) infection. Interleukin (IL)-12 is a cytokine that has been shown to be a potent antiviral cytokine. The aim of this work is to investigate the association of IL-12 B gene polymorphism with staging of liver disease in chronic HCV patients. Methods: This cross sectional study was carried out in tropical medicine department, Tanta university hospital, Egypt, on 120 chronic HCV patients with various stages of liver disease and 30 healthy subjects served as control. All the participants were tested for IL- 12 B (p40) gene polymorphism. Results: the frequency of AA genotype was higher in HCV patients with decompensated cirrhosis and in HCV patients with Hepatocellular carcinoma (HCC). However, the CC genotype was less detected in all groups, with the lowest percentage (6.6%) detected in decompensated cirrhosis and HCC patients. Conclusions: AA genotype presented more frequently in late stages of HCV chronically ill patients, while, CC genotype had no significant association with staging of liver disease and had low frequency especially in late stages of liver disease.

Introduction: Acinetobacter baumannii has emerged as an important nosocomial pathogen in the past decades. Due to the prevalence of A. baumannii across the world, suitable typing methods to investigate the epidemiological distribution of the organism have been developed. The aim of this study was to investigate the epidemiological and molecular diversity of A. baumannii strains isolated from nosocomial infections of hospitalized children in Children Medical Center Hospital (CMC), an Iranian referral hospital, in Tehran, Iran. Material and Methods: A total of 27 non-duplicate clinical A. baumannii isolates were collected during October 2013 to March 2014 and tested for antimicrobial resistance to several antibiotic agents. The genetic similarity of the strains was investigated by amplification of Random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) method. Results: One predominant RAPD profile (type B) was identified in 15 strains (56% of all typed isolates). Other clusters depicted in the dendrogram, namely A, C, and D comprised 6 (22%), 5 (19%) and 1 (3%) isolates, respectively. All A. baumannii strains were resistant to all antibiotics except colistin. Conclusion: This study highlights the clonal spread of multidrug-resistant A. baumannii in our hospital. Therefore, the factors responsible for dissemination of such isolates need to be identified, controlled, and prevented to avoid major outbreaks.

Background: Bloodstream infections (BSI) are considered as a serious cause of morbidity and mortality in children. The aim of this study was to report the common Gram-positive bacteria (GPB) responsible for bloodstream infections in children and determine their antimicrobial resistance patterns in Children Medical Center (CMC) Hospital, Tehran, Iran. Methods: This retrospective study was conducted within a six-year period (March 2011 to September 2016) for pediatric patients with BSI. Standard bacteriological methods were performed for identification of the bacteria. Antimicrobial susceptibility tests were evaluated by using the disk diffusion method according to the CLSI recommendations. Results: Among 68233 blood cultures, 2349 isolates were obtained which 59% of them (N=1393) were GPB and 41% (n=956) were Gram-negative. The most common GPB isolates were Coagulase negative Staphylococcus (CoNS) (N= 609, 44%), followed by Staphylococcus aureus (N=319, 23%), Enterococcus spp. (N=139, 10%), Streptococcus pneumonia (N= 106, 8%), Streptococci viridans (N= 180, 13%) Micrococcus spp. (N=24, 1.7%) and Streptococcus group B (N= 16, 1%). The rate of methicillin resistance in S. aureus and CoNS was 47% (N=116/246) and 91% (N=557/609), respectively. Isolates of S. pneumoniae showed high-level of resistance to trimethoprim/sulfamethoxazole (N=28/33, 85%) and erythromycin (N=59/91, 65%). S. viridans isolates and Micrococcus spp. were highly sensitive to linezolid (100%). All of the tested isolates of Streptococcus group B were sensitive to all the antibiotics used in this study. Among Enterococcus spp., 52% (N=69/133) of the m were resistant to vancomycin. Conclusions: Our results emphasize the importance of a valuable guide in identifying resistance trends and selecting appropriate antibiotic.

Background: The unsatisfactory treatment options for Visceral Leishmaniasis (VL), need identification of new drug targets. Among natural products, Alkaloids have been proved to be highly effective against number of diseases. In Leishmania, UDP-galactopyranosemutase (UGM) is a critical enzyme required for cell wall synthesis and thus a drug target for structure based drug designing against L. donovani. Objective: The aim was to build the homology model of UDP galactopyransemutase and investigate the interaction of selected alkaloids with this modeled UDP galactopyranosemutase by molecular docking. Methodology: Since no crystal structure record has been found with this protein, a homology modeling was performed and a three dimensional structure of L. donovani UGM was created using MODELLER v9.9, structure quality was validated using PROCHECK and QMEAN programs which confirms that the structure is reliable. Further Molecular docking was performed with previously reported15 alkaloids. Results: It was found that Protopine with a binding energy of -12.39Kcal/mole, binds at Flavin adenine dinucleotide (FAD) biding site. Conclusion: It was concluded that Protopine, an alkaloid could interrupt the functional aspect of L. donovani UGM and thus may be useful for drug designing studies. These finding would contribute to the understanding of the effect of drug on the parasite.

Background: Production of Beta-Lactamase enzymes, especially extended- spectrum Beta -Lactamases (ESBL), is a primary mechanism of resistance in these bacteria.The purpose of this study was detection of blaTEM, blaSHV, blaCTXM, blaCTX-M-15, blaPERand blaVEBin K. pneumoniae, isolated from clinical specimens by the PCR method and antibiotic susceptibility patterns in these strains isolated. Materials and Methods: During a period from October 2015 to July 2016, 52 K. pneumoniae isolates were collected from general hospitals in the city of Sanandaj, Iran. After identifying the strains by biochemical testing, the disc diffusion method was used for determining antimicrobial susceptibility and screening the ESBL-producing isolates. Detection of blaTEM, blaSHV, blaCTX-M, blaCTX-M-15, blaPER and blaVEBESBL-producing K. pneumoniae was carried out by PCR. Results: Out of 52-collected K. pneumoniae, highest and lowest rates of resistance related to co-trimoxazole with 67.3 % and amikacin with 30.7 %. 55.7% identified as MDR and 69.23% were ESBL-producing K. pneumoniae.blaSHV was the most prevalent gene in ESBL-producing K. pneumoniae. blaTEM,blaCTX-M,blaCTX-M-15 producing K. pneumoniae strains showed higher rates of drug resistant compared with negative strains (P < 0.05). Conclusion: Results of this study showed that the prevalence rate of ESBL-producing K. pneumoniae isolates is increasing in MDR strains, which raises concerns regarding the treatment of K. pneumoniae. Therefore, molecular research in the field of antimicrobial resistance of bacteria is essential to prevent the spread of resistant strains.

Background: Human infectious diseases are caused by various pathogens including bacteria, fungi, viruses, parasites, and protozoans. These infectious agents are controlled by using synthetic drugs as well as natural sources. Objective: The aim of current study was to evaluate the antibacterial effect of Rumex hastatus against clinical bacterial pathogens. Methods: In current research antibacterial effect of Rumex hastatus was analyzed against seven clinical pathogenic bacteria such as Escherichia coli, Serratia marcescens, Streptococcus pyogenes, Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa through agar well diffusion method. The boiled extract was used for the phytochemical screening, antioxidant potential, thin layer chromatography, bio-autography, and spot screening. Genomic DNA was extracted to find the DNA protection effect of R. hastatus. Results: Antibacterial results showed that diethyl ether extract has the maximum inhibition of S. pyogenes (9.66 ± 0.57 mm). Acetone and diethyl ether extracts showed moderate inhibition of K. pneumoniae (6.33 ± 1.52 mm and 5.66 ±1.15 mm) and S. aureus (6.33 ± 1.52 mm and 5.66 ± 0.57 mm). Similarly, chloroform extract indicated moderate inhibition of S. pyogenes (5.66 ± 1.15 mm). Ethanol extract had low or even no effect on the growth of bacteria. Genomic DNA extraction also encouraged the antibacterial effect of R. hastatus. Various phytochemical constituents such as ketoses, oligosaccharides, amino acids, amines, sugars, flavonoids, and antioxidant constituents were detected. TLC-Bioautography and spot screening results revealed the potential use of R. hustatus as an antibacterial agent. Conclusion: It was concluded that most of the tested fractions appeared as an important source for the discovery of new antimicrobial drugs.

Pubic osteomyelitis is a rare disease usually results from various gynecologic and urologic surgeries. We present a-78 year old-woman admitted to the Infectious Department of Imam Khomeini Hospital in June 2014 with pubic osteomyelitis caused by pseudomonas aeruginosa followed by hysterectomy.