Protease inhibitors as potential antiviral agents for the treatment of picornaviral infections

Wang, Q. May

doi:10.1007/978-3-0348-8730-4_5

Cited by 16 publications

(8 citation statements)

References 95 publications

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“…Clarifying the etiology of every acute respiratory tract infection and providing adequate treatment based on laboratory diagnosis is of particular importance to prevent overprescription of antibiotics (20). In addition, antiviral compounds for the treatment of picornavirus infections may soon be available (8,15,26). Considered in this light, rapid and reliable detection of the infecting agents in acute respiratory tract infections is not only of academic interest but will provide the prerequisite for specific treatment of RV infections.…”

Section: Discussionmentioning

confidence: 99%

Early Detection of Acute Rhinovirus Infections by a Rapid Reverse Transcription-PCR Assay

2001

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The development of a rhinovirus (RV)-RNA-specific reverse transcription (RT)-PCR assay is complicated by the close homology between the RV and enterovirus (EV) genomes in the highly conserved 5-noncoding region, which is chosen for primer design in most RT-PCR assays. We have developed a sensitive, rapid, and RV-specific nested RT-PCR assay and have used it to test nasopharyngeal aspirates from 556 patients presenting with acute respiratory tract infections. RV RNA was detected by nested RT-PCR not only in all of 52 samples that were RV positive by virus isolation methods but also in 124 of 367 samples that were negative by virus isolation methods and enzyme-linked immunosorbent assay (ELISA). In addition, in 23 of 137 samples that were positive for a different respiratory virus by virus isolation and/or ELISA, RV RNA was detected by RT-PCR. EVs, adenoviruses, respiratory syncytial viruses, coronaviruses, and influenza and parainfluenza viruses, including clinical isolates as well as stock viruses, were not amplified in our RV-specific RT-PCR assay, indicating that this assay was highly specific. The processing time was less than 2 days for the RT-PCR, as opposed to up to 2 weeks for virus isolation. These results indicate that nested RT-PCR is more sensitive than conventional methods for the detection of RV in patients experiencing acute respiratory tract infections and represents the only reliable tool for the early laboratory diagnosis of RV infections. This is especially important in light of new opportunities for therapy currently being developed.Human rhinoviruses (RVs) cause an estimated one-third to one-half of all acute respiratory tract infections throughout the year (5, 17) and account for the majority of respiratory illnesses during spring and fall (6). Infections with RVs are usually limited to the upper respiratory tract. However, these viruses have also been shown to be involved in acute otitis media (2), sinusitis (22), and lower respiratory tract infections (5, 21).Infants, the elderly, and people with conditions associated with preexisting airway inflammation such as asthma, cystic fibrosis, and tobacco smoking are at especially high risk for severe complications in the course of RV infections, including wheezing, exacerbations of asthma, small-airway obstruction, bronchitis, and pneumonia (6, 10). Due to the existence of more than 100 different RV serotypes, previous infection does not confer complete immunity, and individuals therefore frequently experience reinfection by an other serotype.Enteroviruses (EVs), a genus within the family Picornaviridae, that is distinct from the RVs, may cause quite similar clinical symptoms of acute respiratory tract infections, particularly in young children (16). Both EVs and RVs are singlestranded RNA viruses with a highly conserved 5Ј-noncoding region (5Ј-NCR) common to all serotypes of EVs and RVs.Previously developed reverse transcription (RT)-PCR assays for the detection of RV RNA in respiratory secretions took advantage of the 5Ј-NCR by using several s...

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Section: Discussionmentioning

confidence: 99%

Early Detection of Acute Rhinovirus Infections by a Rapid Reverse Transcription-PCR Assay

2001

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“…They are a significant cause of aseptic meningitis ( ECHO 3,4,6,7,9,11,14,16,30,31), especially chronic meningoencephalitis [78]. They are also associated with maculopapular exanthema ("rubelliform", ECHO 9; "Boston exanthem", ECHO 16), upper respiratory tract disease (ECHO 11,20) and can cause neonatal carditis (ECHO, 9,22), encephalitis (ECHO 11), and hepatitis (ECHO 11).…”

Section: Diseasesmentioning

confidence: 99%

“…Since many reviews are available that cover the field of picornavirus chemotherapy from its beginning [4][5][6][7][8][9][10][11], this paper will review only the current status of chemotherapeutic agents for each of the human pathogen groups in the Picornaviridae from the past several years.…”

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confidence: 99%

Current Status of Anti-Picornavirus Therapies

Barnard

2006

CPD

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Picornaviruses are important human pathogens causing severe morbidity and some mortality with the potential to cause worldwide crippling disease. Currently, there are few treatments for many of the viruses in the Picornaviridae, For rhinoviruses, there are no approved treatments, although ruprintrivir looks promising in clinical trials and pyridazinyl oxime ethers may prove useful. Poliovirus treatments are needed to supplement the World Health Organization's polio eradication plan in order to treat infections caused by reversion of the attenuated vaccine virus and to supplement vaccine coverage control in polio endemic areas. However, no promising compounds for treatment of poliovirus have been developed due to the efficacy of the vaccines in use. Broad-spectrum inhibitors developed for other picornavirus may be useful for poliovirus infections. Coxsackievirus infections in children and in infants are being treated with pleconaril with some efficacy in reducing mortality and improving recovery, albeit the treatment is often on a compassionate use basis. There are no therapies for echovirus infections. Very little drug discovery research is being done to develop inhibitors for echovirus infections, probably due to the broad-spectrum inhibition exhibited by capsid binding agents and protease inhibitors discovered for treatment of other picornaviruses. For example, pyridazinyl oxime ethers are inhibitory to most echoviruses. Treatments for enterovirus infections are also limited, although in a small clinical trial, milrinone seemed to reduce mortality and improve recovery from EV71-induced pulmonary edema. Thus, these results strongly emphasize the need for the development of potent and nontoxic compounds for the treatment of picornavirus infections.

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“…Subsequent studies are in progress, aiming at another rhinoviral protease (i.e. 2A) as a target for antirhinoviral therapy [73,74].…”

Section: Poor Pills: An Overview Of Therapeutic Strategiesmentioning

confidence: 99%

The cold case: Are rhinoviruses perfectly adapted pathogens?

Dreschers

Dumitru

Adams

et al. 2006

Cell. Mol. Life Sci.

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Rhinoviruses, which cause common cold, belong to the Picornaviridae family, small non-enveloped viruses (diameter 15-30 nm) containing a single-stranded RNA genome (about 7 kb). Over 100 different rhinoviral serotypes have been identified thus far, establishing rhinoviruses as the most diverse group of Picornaviridae. Based on receptor binding properties, rhinoviruses are divided into two classes: the major group binding to intracellular adhesion molecule-1 and the minor group binding to the very low density lipoprotein receptors. Interactions between virus and the receptor molecules cause a conformational change in the capsid, which is a prerequisite for viral uptake. Rhinoviruses trigger a chemokine response upon infection that may lead to exacerbation of the symptoms of common cold, i.e. asthma and inflammation. The following review aims to summarize the knowledge about rhinoviral infections and discusses therapeutical approaches against this almost perfectly adapted pathogen.

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Protease inhibitors as potential antiviral agents for the treatment of picornaviral infections

Cited by 16 publications

References 95 publications

Early Detection of Acute Rhinovirus Infections by a Rapid Reverse Transcription-PCR Assay

Early Detection of Acute Rhinovirus Infections by a Rapid Reverse Transcription-PCR Assay

Current Status of Anti-Picornavirus Therapies

The cold case: Are rhinoviruses perfectly adapted pathogens?

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