Pleconaril
Encyclopedia
Pleconaril is an antiviral drug
being developed by Schering-Plough
for prevention of asthma
exacerbations and common cold
symptoms in asthmatic subjects exposed to picornavirus
respiratory infections. Although the formulation used by Schering-Plough is a nasal spray
, pleconaril is orally bioavailable
, and is active against viruses in the Picornaviridae family, including Enterovirus
and Rhinovirus
.
, and licensed to ViroPharma
in 1997. ViroPharma developed it further, and submitted a New Drug Application
to the United States
Food and Drug Administration
(FDA) in 2001. The application was rejected, citing safety concerns; and ViroPharma re-licensed it to Schering-Plough in 2003. The Phase II clinical trial
was completed in 2007.
(the outer "shell") of picornavirus
es. In enteroviruses, this prevents the virus from exposing its RNA
, and in rhinoviruses it also prevents the virus from attaching itself to the host cell.
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
being developed by Schering-Plough
Schering-Plough
Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co...
for prevention of asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
exacerbations and common cold
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
symptoms in asthmatic subjects exposed to picornavirus
Picornavirus
A picornavirus is a virus belonging to the family Picornaviridae. Picornaviruses are non-enveloped, positive-stranded RNA viruses with an icosahedral capsid. The genome RNA is unusual because it has a protein on the 5' end that is used as a primer for transcription by RNA polymerase...
respiratory infections. Although the formulation used by Schering-Plough is a nasal spray
Nasal spray
Nasal sprays come in a variety of forms. Medicated such as Astelin, Afrin and Nasonex and natural such as Sinusoothe and Sterimar. Although delivery methods vary, most nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism.-Antihistamine nasal...
, pleconaril is orally bioavailable
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
, and is active against viruses in the Picornaviridae family, including Enterovirus
Enterovirus
Enteroviruses are a genus of ssRNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the...
and Rhinovirus
Rhinovirus
Human rhinoviruses are the most common viral infective agents in humans and are the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures between 33–35 °C , and this may be why it occurs primarily in the nose...
.
History
Pleconaril was originally developed by Sanofi-AventisSanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
, and licensed to ViroPharma
ViroPharma
ViroPharma Incorporated, a pharmaceutical company, develops and sells drugs that address serious diseases treated by physician specialists and in hospital settings...
in 1997. ViroPharma developed it further, and submitted a New Drug Application
New drug application
The New Drug Application is the vehicle in the United States through which drug sponsors formally propose that the Food and Drug Administration approve a new pharmaceutical for sale and marketing...
to the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) in 2001. The application was rejected, citing safety concerns; and ViroPharma re-licensed it to Schering-Plough in 2003. The Phase II clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
was completed in 2007.
Mechanism of action
Pleconaril binds to a hydrophobic pocket in VP1, the major protein which comprises the capsidCapsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
(the outer "shell") of picornavirus
Picornavirus
A picornavirus is a virus belonging to the family Picornaviridae. Picornaviruses are non-enveloped, positive-stranded RNA viruses with an icosahedral capsid. The genome RNA is unusual because it has a protein on the 5' end that is used as a primer for transcription by RNA polymerase...
es. In enteroviruses, this prevents the virus from exposing its RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
, and in rhinoviruses it also prevents the virus from attaching itself to the host cell.