Recent Patents on Anti-Infective Drug Discovery (v.9, #2)

Recent Developments in Anti-dotes Against Anthrax by Neha Dhasmana, Lalit K. Singh, Asani Bhaduri, Richa Misra, Yogendra Singh (83-96).
The etiologic agent of disease anthrax, Bacillus anthracis, causes recurrent outbreaks among the livestock and intermittent infections in humans across the world. Controlling animal infections by vaccination can minimize the incidence of disease in humans. Prevention of anthrax in occupationally exposed personnel is achieved through vaccination with either live spores or precipitates of culture supernatants from attenuated strains of B. anthracis. However, anthrax vaccination of the large human population is impractical as well as inappropriate. Broad-range antibiotics like amoxicillin, ciprofloxacin, clindamycin, streptomycin, and penicillin G are recommended for the treatment of human anthrax infections, but the threat of antibiotic resistant strains always remains. Moreover, in the absence of any specific symptom (s) during early infection, the diagnosis of anthrax is delayed causing elevated levels of anthrax toxin component which could be fatal. For these reasons, there is a need to develop new antimicrobial agents against virulent B. anthracis to effectively combat this fatal pathogen. Over the last two decades, extensive studies have been carried out to develop specific inhibitors against virulence factors of B. anthracis such as capsule, protective antigen, lethal factor and edema factor. Research has also been focused in developing inhibitors of anthrax toxin receptors (including the use of receptor decoys) and host furin endoproteases which are required for activation of toxin. This review highlights the recent progress made in developing the diverse countermeasures for anthrax infections targeting B. anthracis virulence factors and their counterparts in host.

Current Status of Chemically Synthesized Inhibitors of Ebola Virus by Anthony P. Cardile, Douglas L. Mayers, Sina Bavari (97-103).
The current Ebola virus outbreak is unprecedented in its scope and international impact. Given that there are currently no approved antivirals to treat Ebola virus, there is urgency to conduct more rapid development and evaluation of Ebola antivirals. Recently, the World Health Organization identified a number of antivirals as high priority to include AVI-6002 (AVI-7537 and AVI-7539), BCX4430, brincidofovir, favipiravir, and TKM-100802. This review describes these chemically synthesized inhibitors of Ebola virus, relevant patent development and gives an update on their current status.

Current Developments in Therapeutic and Diagnostic Strategies for Q Fever: Glimpses of Patent Analysis by Rashi Chauhan, Gulshan Wadhwa, Sanjeev K. Sharma, Chakresh K. Jain (104-111).
Coxiella burnetii is an infectious and etiological agent responsible for causing Q fever. There are mainly two forms of the Q fever that are chronic and acute. Though the acute type is usually linked with symptoms like pneumonia and hepatitis, the chronic form is shown to have mortality rate of 5%. Percentage of mortality rate might increases from 5% to 25% if left untreated. The present treatments of disease include the recommended dose of drugs and vaccine. Presently, extensive attempt is in progress to find novel therapies to combat the disease. This review is projected to provide a brief introduction of C. burnetii and Q fever while emphasizing therapeutics, prophylactic measures and diagnostic applications based on recent patents prospects.

New Perspectives of HIV/AIDS Therapy Study by Da-Yong Lu, Ting-Ren Lu, Jin-Yu Che, Hong-Ying Wu, Bin Xu (112-120).
HIV/AIDS (acquired immune deficient syndrome), a human infectious disease was once listed as the No. 1 disease killer in US (1993). After the invention of antiviral drug cocktails-high active anti-retroviral therapy (HAART), most HIV-infected patients can survive much longer than with single antiviral drugs or vaccines alone. However, it turns out to be a chronic disease owing to being incapable to eradicate HIV from infectious patients. Furthermore, potential newly outbreak of HIV epidemics caused by widespread drug-resistance or viral mutations is still looming over the globe. In order to counteract these drawbacks and possibilities of HAART, many hurdles must be passed. More creative and revolutionary ideas and worldwide cooperation efforts among academics, drug developers and governmental funding bodies must be encouraged and promoted. In this perspective, many important drawbacks and weaknesses relating to HIV/AIDS therapies are outlined and possible future solutions are highlighted.

Cancer Targeted Magic Bullets for Effective Treatment of Cancer by Preeti Aneja, Mahfoozur Rahman, Sarwar Beg, Shivali Aneja, Vishal Dhingra, Rupali Chugh (121-135).
Cancer is a multifaceted disorder with serious threat across the globe. The vision for accomplishing an effective treatment strategy for cancer has always been a major concern worldwide. Although conventional drug therapy, esp. the chemotherapeutics provide benefits upto certain extent for treatment and management of cancers, yet it possesses umpteen challenges in terms of the associated side effects and adverse effects, lack of targeting ability, multi-drug resistance, poor patient acceptance and compliance, etc. at the desired site. To overcome these problems, the nanomedicines have been evolved as an effective and cost-effectual alternative for treatment of cancer. Inspiring from the concept of magic bullet, the world is moving towards developing the surface modified nanocarriers, which not only provide effective drug delivery but also allows site-specific monitoring of the cancer cells through in vivo diagnostic imaging. The present review endeavors to provide an explicit account on various drug targeting strategies employed for nanomedicines like active targeting, passive targeting, magnetic targeting, physical targeting and ultrasound targeting, etc, followed by their utility in the treatment of a particular type of cancer. According to the recent market survey, many nanocarrier-based drug delivery systems have been approved by USFDA, EMEA, MHRA and other global regulatory agencies, testify the high degrees of acceptance of the nanomedicines for treatment of cancer, while many products are under the preclinical and clinical development phases. Thus, for the translation of such technologies into the clinic, the pharma industry needs to be metamorphosing for a change in its culture of developing the traditional therapeutics.

Purpose: Diarrhea and dehydration caused by enteric infections is a major factor of morbidity and mortality worldwide. Secretory diarrhea can be devastating especially among infants, children, and HIV infected people and can result in death of more than 50% of its victims for without adequate rehydration, patients are at maximum risk during the first 6-18 hours. Hence, it is a leading cause of morbidity and mortality worldwide. Diarrhea is experienced by over 50% of AIDS patients at some time or other during the course of their illness, which is an important cause of increased morbidity and mortality in them. Currently, the standard-of-care therapy focuses only on rehydration therapy to combat dehydration and antibiotic therapy that targets the infectious agent only. Though, antimicrobial drugs have been the key treatment for diarrhea but, with the emergence of resistant strains the search for novel targets/drugs is on, for diarrhea still continues to kill millions.
Methods: A literature search was done using secretory diarrhea and Crofelemer, as key words using PubMed (Medline), ProQuest, Cochrane Library, Medscape and Google Scholar search engines from January 2012 to December 2014. The types of articles included in this review were original research, review papers, recent patents and editorials from various medical schools across the globe. Though, it was practically not possible to include all studies, one can marvel at all the proclaimed mechanism of action of Crofelemer in this study.
Results: Crofelemer, a channel blocker of intestinal chloride channels such as the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and the Calcium Activated Chloride Channels (CaCCs) plays significant roles in providing symptomatic relief in secretory diarrhea.
Conclusion: Crofelemer is a first-in-class agent that possesses a unique mechanism of action through dual inhibition of both the intestinal chloride channels in secretory diarrhea.

Evaluation of Urinary Interleukin-8 Levels in Patients with Spinal Cord Injury by Monireh Rahimkhani, Alireza Mordadi, Sajad Varmazyar, Ali Tavakoli (144-149).
Background: Interleukins are a group of cytokines responsible for regulating inflammatory and infectious responses. Interleukin-8 plays an important role in chemotaxis and functioning of leukocytes and is locally produced in infected tissues; it is seen in abundance in the urine of individuals with Urinary Tract Infection.
Material & Methods: Midstream sterile urine sampling was performed in different patients admitted to the Spinal Cord Injury (SCI) research center. The samples were tested to determine the level of IL-8 through the ELISA method. The commercial kit used for this study was an R & D kit built in Germany.
Results: The mean level of IL-8 was 369.59pg/ml and 75.42pg/ml in male and female patients respectively. Among the 97 patients under study, 87 (89.7%) were IL-8 positive (>10 pg/ml) and 10 patients were IL-8 negative (<10 pg/ml). Among the 87 IL-8 positive subjects, 64 patients had no UTI symptoms, while 23 did.
Conclusion: SCI patients should have their urinary IL-8 levels measured on a routine and periodic basis, irrespective of their SCI severity or the presence or absence of UTI symptoms. The timely and effective diagnosis & treatment of UTI can prevent the irreversible complications caused by frequent UTI and resistance to treatment in this group of patients.

Patent Selections: (152-154).