Title:Antiviral Drug Targets of Single-Stranded RNA Viruses Causing Chronic Human Diseases
Volume: 21
Issue: 2
Author(s): Dhurvas Chandrasekaran Dinesh*, Selvaraj Tamilarasan, Kaushik Rajaram and Evžen Bouřa*
Affiliation:
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague,Czech Republic
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague,Czech Republic
Keywords:
RNA viruses, chronic diseases, drug targets, inhibitors, antivirals, HIV, hepatitis, flaviviruses, protein structures.
Abstract: Ribonucleic acid (RNA) viruses associated with chronic diseases in humans are major
threats to public health causing high mortality globally. The high mutation rate of RNA viruses helps
them to escape the immune response and also is responsible for the development of drug resistance.
Chronic infections caused by human immunodeficiency virus (HIV) and hepatitis viruses (HBV and
HCV) lead to acquired immunodeficiency syndrome (AIDS) and hepatocellular carcinoma respectively,
which are one of the major causes of human deaths. Effective preventative measures to limit
chronic and re-emerging viral infections are absolutely necessary. Each class of antiviral agents targets
a specific stage in the viral life cycle and inhibits them from its development and proliferation. Most
often, antiviral drugs target a specific viral protein, therefore only a few broad-spectrum drugs are
available. This review will be focused on the selected viral target proteins of pathogenic viruses containing
single-stranded (ss) RNA genome that causes chronic infections in humans (e.g. HIV, HCV,
Flaviviruses). In the recent past, an exponential increase in the number of available three-dimensional
protein structures (>150000 in Protein Data Bank), allowed us to better understand the molecular
mechanism of action of protein targets and antivirals. Advancements in the in silico approaches paved
the way to design and develop several novels, highly specific small-molecule inhibitors targeting the
viral proteins.