Therapies for coronaviruses. Part I of II – viral entry inhibitors

Abstract

Background: Severe acute respiratory syndrome (SARS) coronavirus emerged fleetingly in the winter of 2002 and again in the winter of 2003, resulting in the infection of ∼ 8000 people and the death of ∼ 800. The identification of the putative natural reservoir suggests that a re-emergence is possible. The functions of many coronaviral proteins have now been elucidated, resulting in many novel approaches to therapy. Objective: To review anticoronaviral therapies based on inhibition of viral entry into the host cell and to cast light on promising approaches and future developments. Method: The published literature, in particular patent publications, is searched for relevant documents. The information is organized and critiqued. Results/conclusion: The approaches to combating coronaviral infections are built on the foundation of antivirals against other viruses and the fundamental insights gained by dissection of the coronaviral lifecycle. These approaches include the prevention of viral entry, reviewed here, and interference with the intracellular lifecycle of the virus in the infected cell, reviewed next. Of the viral-entry inhibitors, monoclonal antibodies have demonstrated efficacy, clinical application in other viral infections, and the potential to impact a future epidemic. Moreover, combinations of monoclonal antibodies have been shown to have a broader spectrum of antiviral activity.

Keywords::

• ACE2
• cathepsin L
• coronavirus
• heptad repeat
• monoclonal antibody
• SARS
• SARS-CoV
• severe acute respiratory syndrome