Anti-virus reagents targeting the capsid protein assembly

Abstract

Anti-viral therapy has made remarkable strides in improving the quality of life of infected individuals over the past few decades. However, the emergence of adverse side effects and drug resistance highlights the need for alternate drugs with either different structures or distinct mechanisms of action. The virus capsid is an attractive therapeutic target owing to its high sequence conservation and essential role in the virus life cycle. The capsid protein can be affected by small molecules at different positions in several combinations, both in early and late steps in the cycles of virus infection and replication. Therefore, a variety of small molecules that bind to the capsid proteins have been developed, and some of them have shown promise for pre-clinical therapeutic development. In this review, we focus on the recent advances on small molecules targeting the capsid protein of several clinically related spherical viruses such as the hepatitis B virus (HBV), human immunodeficiency virus (HIV) and human papillomavirus (HPV), together with filoviruses such as Ebola in several distinct classes of (i) synthetic organics, (ii) natural products and their derivatives, and (iii) peptides. Hopefully, some of these preclinical capsid inhibitors will be approved for therapy within the next few years.