Author/Editor		Marc, Gašper
Title		Učinkovine v zdravljenju okužbe z virusom človeške imunske pomanjkljivosti (HIV)
Translated title		Drugs in therapy of HIV infection
Type		članek
Source		Farm Vestn
Vol. and No.		Letnik 49, št. Spec Issue
Publication year		1998
Volume		str. 87-98
Language		slo
Abstract		Design and development of anti-HIV drugs is one of the most exciting and rapidly evolving fields or medicinal chemistry. In 1983, HIV was isolated and since them hundreds of agents has been tested on anti-HIV activity. First successful anti-HIV agent was zidovudin, which was introduced in clinical practice in 1987 and still plays an important role in anti-HIV therapy. Several new drugs from the group of nucleoside reverse transcriptase inhibitors followed zidovudine Among them, the most important are didanosine, zalcitabine, stavudine and lamivudine. Beside nusleoside analogues, non-nucleoside reverse transcriptase inhibitors were discovered. They interact in a noncompetitive way with an allosteric site, thereby inactivating the enzyme. Third group of anti-HIV agents, HIV protease inhibitors, was created by rational drug design approach. Development of protease inhibitors was made possible by advanced knowledge of virus life-cycle, threedimensional structure of the enzyme and computeraided molecular modelling. Currently, four protease inhibitors (saquinavir, indinavir, ritonavir and nelfinavir) are used in clinical practice.
Summary		Načrtovanje in razvoj učinkovin proti virusu človeške imunske pomanjkljivosti (HIV) je eno izmed najhitreje razvijajočih se področij farmacevtske kemije. Izolaciji HIV leta 1983 je sledilo intenzivno iskanje primernih učinkovin in že leta 1987 je bilo v klinično prakso vpeljano prvo zdravilo, zidovudin, ki ima tudi danes pomembno mesto v zdravljenju. Sledilo mu je več učinkovin iz skupine zaviralcev reverzne transkriptaze, med katerimi so najpomembnejši didanozin, zalcitabin, stavudin in lamivudin. Nukleozidnim analogom je sledilo odkritje nenukleozidnih zaviralcev reverzne transkriptaze, ki stopajo interakcijo z alosteričnim vezavnim mestom encima in ga tako inaktivirajo. Tretjo pomembno skupino učinkovin sestavljajo zaviralci proteaze HIV, ki so plod racionalnega načrtovanja, ki ga je omogočilo poglobljeno razumevanje virusovega razvojnega kroga; poznavanje tridimenzionalne strukture encima in računališko podprto modeliranje. Trenutno so že v uporabi štiri učinkovine (sakvinavir, indinavir, ritonavir in nelfinavir), veliko pa jih je tudi v različnih fazah kliničnih testiranj.
Descriptors		ACQUIRED IMMUNODEFICIENCY SYNDROME ANTIVIRAL AGENTS HIV REVERSE TRANSCRIPTASE INHIBITORS PROTEASE INHIBITORS