Glycoprotein targeted therapeutics: a new era of anti-herpes simplex virus-1 therapeutics

Abstract

Herpes simplex virus type-1 (HSV-1) is among the most common human pathogens worldwide. Its entry into host cells is an intricate process that relies heavily on the ability of the viral glycoproteins to bind host cellular proteins and to efficiently mediate fusion of the virus envelope with the cell membrane. Acquisition of HSV-1 results in a lifelong latent infection. Because of the cycles of reactivation from a latent state, much emphasis has been placed on the management of infection through the use of DNA synthesis inhibitors. However, new methods are needed to provide more effective treatment at earlier phases of the viral infection and to prevent the development of drug resistance by the virus. This review outlines the infection process and the common therapeutics currently used against the fundamental stages of HSV-1 replication and fusion. The remainder of this article will focus on a new approach for HSV-1 infection control and management, the concept of glycoprotein-receptor targeting.

Figure 1

Viral Attachment and Entry. HSV-1 attachment to host cells is mediated by the binding of gB and/or gC to cell surface co-receptor, heparan sulfate. Next, the entry or penetration step is mediated through the collaborative efforts of glycoproteins gB, gD, gH, and gL. This requires binding of gD with one of its receptors, which facilitates a conformational change in gD that allows it to recruit gB, and gH-gL to form a fusion complex to facilitate capsid penetration into the host cytosol.