Achievements and Challenges in Antiviral Drug Discovery

Littler, Eddy; Öberg, Bo

doi:10.1177/095632020501600302

Cited by 53 publications

(35 citation statements)

References 85 publications

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“…Half a century has passed since the debut of the development of antiviral drugs (103). However, only six drugs have been approved by the FDA for the treatment of hepatitis B since then: Immune modulators, such as interferon alpha (i.e., conventional INF-α 2a, conventional INF-α 2b and peglayted INF-α 2a); and direct antiviral drugs, including Lamivudine, Adefovir, Entecavir, Telbivudine, and Tenefovir (7).…”

Section: Resultsmentioning

confidence: 99%

Hepatitis B and its Relationship With Oxidative Stress

Alavian

Showraki

2016

Hepat Mon

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ContextDespite the great breakthroughs we have witnessed in the last 50 years in the prevention, diagnosis, and treatment of hepatitis B, we are still far from eradicating or even curing the disease. Achieving further progress in controlling this disease will not be possible without discovering the exact pathogenesis behind it. One prime suspect in the pathogenesis of various diseases is oxidative stress. This review will exclusively explore hepatitis B in the context of oxidative stress to obtain a more comprehensive clinical perspective on its pathogenesis and eventual medical therapy.Evidence AcquisitionWe systematically searched PubMed, Google Scholar, Web of Science, EMBASE, and Scopus using an extensive list of keywords in the following three categories: 1) Hepatitis B and oxidation 2) Hepatitis B and antioxidant system 3) Effects of approved anti-hepatitis B drugs on redox status. All relevant articles were obtained and reviewed carefully after the exclusion criteria were deployed.ResultsThere is great evidence indicating extensive oxidative stress occurs in hepatitis B. This oxidative stress takes place on multiple levels, including lipid peroxidation, DNA oxidation, protein oxidation, and reactive oxygen and nitrogen species production. However, there are also conflicting results with regard to antioxidant therapy and antioxidant status in hepatitis B, some of which may be explained by the concept of “compensatory gaps.” Nevertheless, further studies are indicated to reach a more thorough judgment.ConclusionsDespite the presence of vast oxidative stress in hepatitis B, antioxidant therapy is not always effective as a treatment strategy, especially considering that antioxidants can act as “double-edged swords” or antioxidants; if not used at the right time or place or in the right combination, these substances can easily become pro-oxidants. Therefore, several studies will be needed to determine suitable antioxidant therapies. We propose the “2-step Combined Antioxidant Adjuvant Therapy for hepatitis B (2CAAT Hep B)” as a new strategy for antioxidant adjuvant therapy. We also suggest developing an international platform and database for antioxidant adjuvant therapy in hepatitis B (IPAATH and IDAATH) to canalize this field of research in a standardized direction, especially when complexity is a problem.

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Section: Resultsmentioning

confidence: 99%

Hepatitis B and its Relationship With Oxidative Stress

Alavian

Showraki

2016

Hepat Mon

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“…In 1964, amantadine was reported as an inhibitor of influenza, and was particularly useful for prophylaxis (infection prevention) [87]. Though this class of drug is susceptible to viral development of drug resistance, it also provided a basis for the more recent development of neuraminidase inhibitors (generic names zanamivir and oseltamivir), which can be effective in preventing influenza infection, as well as reducing the severity and duration of infection, particularly if administered within 48 hours of symptom onset [88]. Neuraminidase inhibitors are the class of antiviral most commonly used today: their development was an important milestone in increasing response capabilities to influenza.…”

Section: 1970s–2000s: Computers Drugs and The Wtomentioning

confidence: 99%

Reviewing the History of Pandemic Influenza: Understanding Patterns of Emergence and Transmission

2016

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For centuries, novel strains of influenza have emerged to produce human pandemics, causing widespread illness, death, and disruption. There have been four influenza pandemics in the past hundred years. During this time, globalization processes, alongside advances in medicine and epidemiology, have altered the way these pandemics are experienced. Drawing on international case studies, this paper provides a review of the impact of past influenza pandemics, while examining the evolution of our understanding of, and response to, these viruses. This review argues that pandemic influenza is in part a consequence of human development, and highlights the importance of considering outbreaks within the context of shifting global landscapes. While progress in infectious disease prevention, control, and treatment has improved our ability to respond to such outbreaks, globalization processes relating to human behaviour, demographics, and mobility have increased the threat of pandemic emergence and accelerated global disease transmission. Preparedness planning must continue to evolve to keep pace with this heightened risk. Herein, we look to the past for insights on the pandemic experience, underlining both progress and persisting challenges. However, given the uncertain timing and severity of future pandemics, we emphasize the need for flexible policies capable of responding to change as such emergencies develop.

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“…A preexisting viral infection can theoretically be targeted by an antiviral or a therapeutic vaccine. Successful antivirals have been developed for the treatment of some viral infections, including diseases such as HIV and influenza (19), but not against viruses such as HPV. A therapeutic vaccine against HPV infection would be highly desirable to prevent the cancer-associated complications of HPV infection, which only develop after many years of infection.…”

mentioning

confidence: 99%

Prophylactic human papillomavirus vaccines

Lowy¹

2006

Journal of Clinical Investigation

345

217

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Human papillomavirus (HPV) infection causes virtually all cases of cervical cancer, the second most common cause of death from cancer among women worldwide. This Review examines prophylactic HPV subunit vaccines based on the ability of the viral L1 capsid protein to form virus-like particles (VLPs) that induce high levels of neutralizing antibodies. Following preclinical research by laboratories in the nonprofit sector, Merck and GlaxoSmithKline are developing commercial versions of the vaccine. Both vaccines target HPV16 and HPV18, which account for approximately 70% of cervical cancer. The Merck vaccine also targets HPV6 and HPV11, which account for approximately 90% of external genital warts. The vaccines have an excellent safety profile, are highly immunogenic, and have conferred complete type-specific protection against persistent infection and associated lesions in fully vaccinated women. Unresolved issues include the most critical groups to vaccinate and when the vaccine's cost may be low enough for widespread implementation in the developing world, where 80% of cervical cancer occurs. Human papillomavirus infection and diseaseOf the 10 million cases of cancer that develop annually throughout the world, more than 15% are estimated to be attributable to infectious agents (1). Infection by human papillomaviruses (HPVs) accounts for approximately 30% of these cancers (~5% of all cancers), with hepatitis B and C viruses and Helicobacter pylori together accounting for another 60% of cancers with an infectious etiology.HPVs infect the stratified squamous epithelia of skin and mucous membranes, where they cause benign lesions, some of which have the potential to progress to invasive cancer. (2-4). HPVs are small, nonenveloped viruses whose approximately 8-kb circular genome encodes 2 structural proteins, L1 and L2, that form the viral capsid, plus several nonstructural proteins that are important for the virus life cycle but are not incorporated into virions. To establish infection, microtrauma or erosion of the overlying epithelial layers is thought to enable HPVs to infect cells of the basal epithelial layer, where the stem cells and other long-lived cells are found (Figure 1). HPV infections tend to last months or years because the viral genome successfully parasitizes these cells and because the virus evades the immune system by limiting most viral gene expression and viral replication to suprabasal cell layers. Most infections are self-limited, presumably because the host eventually mounts a successful immune response.The benign lesions induced by HPVs include nongenital and anogenital skin warts, oral and laryngeal papillomas, and anogenital mucosal condylomata (Figure 2). Anogenital infections are almost always transmitted sexually. Long-term infection by a subset of HPVs can lead to malignant anogenital tumors, including cancers of the anus, penis, vulva, vagina, and cervix (5-7). A proportion of oral cancer is also attributable to HPV (8, 9). While HPV infection has been associated on limited occasions ...

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Achievements and Challenges in Antiviral Drug Discovery

Cited by 53 publications

References 85 publications

Hepatitis B and its Relationship With Oxidative Stress

Hepatitis B and its Relationship With Oxidative Stress

Reviewing the History of Pandemic Influenza: Understanding Patterns of Emergence and Transmission

Prophylactic human papillomavirus vaccines

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