Orthopoxvirus targets for the development of new antiviral agents

Abstract

Investments in the development of new drugs for orthopoxvirus infections have fostered new avenues of research, provided an improved understanding of orthopoxvirus biology and yielded new therapies that are currently progressing through clinical trials. These broad-based efforts have also resulted in the identification of new inhibitors of orthopoxvirus replication that target many different stages of viral replication cycle. This review will discuss progress in the development of new anti-poxvirus drugs and the identification of new molecular targets that can be exploited for the development of new inhibitors. The prototype of the orthopoxvirus group is vaccinia virus and its replication cycle will be discussed in detail noting specific viral functions and their associated gene products that have the potential to serve as new targets for drug development. Progress that has been achieved in recent years should yield new drugs for the treatment of these infections and might also reveal new approaches for antiviral drug development with other viruses.

Fig. 1

Chemical structure of selected inhibitors of orthopoxvirus replication.

Fig. 2

Selected inhibitors of orthopoxvirus replication. The major stages of vaccinia virus replication are represented as indicated by the white text. Representative compounds that interfere with each of the steps are shown in yellow below the stage of replication that they inhibit. Extracellular enveloped virions (EEV), intracellular mature virions (IMV), immature virions (IV), intracellular enveloped virions (IEV), and cell associated enveloped virions (CEV) are also depicted.