Antiviral drug discovery: HIV-1 RNase H, the next hit target

Antiviral drugs are a class of medication used for selectively treating viral infections. In the last three decades, the antiviral drug field has greatly developed through the interaction of several disciplines such as virology, biochemistry, chemistry, structural biology, and have reached enormous achievements. Paradigms of them are the treatments for HSV and HIV-1 infections. The latter is a striking example of the development of drugs which have turned a dreadful disease into a manageable chronic infection. However, still new anti-HIV drugs are needed, particularly drugs targeted to viral functions which are not inhibited yet by the current treatments. The HIV-1 reverse transcriptase-associated ribonuclease H (RNase H) activity is an attractive non traditional target for drug development which has been, so far, little explored. The present review is focused on the approach needed to identify valid RNase H inhibitors and lists the agents which have been reported, until now, to have an impact on the HIV-1 RNase H activity.