Abstract
Several strategies have been developed to fight viral infections, not only in humans but also in animals and plants. Some of them are based on the development of efficient vaccines, to target the virus by developed antibodies, others focus on finding antiviral compounds with activities that inhibit selected virus replication steps. Currently, there is an increasing number of antiviral drugs on the market; however, some have unpleasant side effects, are toxic to cells, or the viruses quickly develop resistance to them. As the current situation shows, the combination of multiple antiviral strategies or the combination of the use of various compounds within one strategy is very important. The most desirable are combinations of drugs that inhibit different steps in the virus life cycle. This is an important issue especially for RNA viruses, which replicate their genomes using error-prone RNA polymerases and rapidly develop mutants resistant to applied antiviral compounds. Here, we focus on compounds targeting viral structural capsid proteins, thereby inhibiting virus assembly or disassembly, virus binding to cellular receptors, or acting by inhibiting other virus replication mechanisms. This review is an update of existing papers on a similar topic, by focusing on the most recent advances in the rapidly evolving research of compounds targeting capsid proteins of RNA viruses.
Highlights
The recent coronavirus pandemic has shown that emerging viruses pose a constant threat that should keep scientists and pharmacists alert
We focus on RNA viruses, with one exception, the hepatitis B virus, where replication depends on the error-prone formation of an RNA intermediate, which stimulates the search for new inhibitors capable of alleviating the problem of new mutants resistant to inhibitors
Hepatitis B virus-transgenic mice were treated with an adenoviral vector carrying fusion protein consisting of hepatitis B-virus (HBV) core protein and a ribonuclease, human eosinophil-derived neurotoxin [25], or the transgenic grass carp with the gene for fusion reoviral capsid protein and staphylococcal nuclease (SN) integrated into its genome was constructed to avoid its reoviral infection [26]
Summary
The recent coronavirus pandemic has shown that emerging viruses pose a constant threat that should keep scientists and pharmacists alert. The search for new antivirals even against currently well-controlled viruses is justified by the risk of the emergence of drug-resistant mutants that occur either spontaneously or are selected in the presence of drugs applied during long-term infections. For the latter reason, new drugs that inhibit viral processes other than the most often targeted replication of the viral genome and virus maturation, are desirable. The patients are dependent on a lifelong treatment with a combination of drugs preferentially targeting different steps of the virus life cycle This approach has significantly extended their life expectancy and quality. Mutations causing resistance to a particular drug mainly do not affect the pathogenicity of the virus, they represent a major problem in the treatment of virus infections and justify the search for alternative drugs, preferably with new targets for combination therapy
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