Antiviral agents reverse transcriptase inhibitors

The replicative cycle of HIV presents many opportunities for the targeting of antiviral agents. The drugs in clinical use are classified as nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NTRTIs), and protease inhibitors (PI). 

Although any of these seven steps could be a druggable target, most of the antiviral agents clinically employed for non-AIDS infections act on the synthesis or assembly of either purines or pyrimidines (steps 3 and 4). For AIDS, reverse transcriptase inhibitors block transcription of the HIV RNA genome into DNA, thereby preventing synthesis of viral mRNA and protein protease inhibitors act on the synthesis of late proteins (steps 5 and 6). 

Zagreb antivenom is a non-proprietary antivenom preparation that can be used as an injected ANTIDOTE to the poison from an adder s bite. However, the systemic allergic and other effects of the venom are rarely serious enough to warrant the use of the antivenom, zalcitabine [ban, inn, usan] (ddC DDC Hivid ) is a synthetic nucleoside analogue, a REVERSE TRANSCRIPTASE INHIBITOR which acts as an ANTIVIRAL AGENT. It is active orally as an ANTI-HIV AGENT. 

The enantiopure A-Ts cyclopentene carboxamide 35, obtained by a [2+2] cycloaddition and an enzymatic resolution, could also be a platform to synthesize the antiviral agent ( )-abacavir 38 (Scheme 41.8), which is a nucleoside analog reverse transcriptase inhibitor used in combination... 

Hurwitz SJ, Schinazi RF (2002) Development of a pharmacodynamic model for HIV treatment with nucleoside reverse transcriptase and protease inhibitors. Antiviral Res 56 115-127 Hurwitz SJ, Tennant BC, Korba BE, Gerin JL, Schinazi RF (1998) Pharmacodynamics of (—)-beta-2, 3 -dideoxy-3 -thiacytidine in chronically virus-infected woodchucks compared to its pharmacodynamics in humans, Antimicrob Agents Chemother 42 2804-2809 Hurwitz SJ, Otto MJ, Schinazi RF (2005) Comparative pharmacokinetics of Racivir, (+/-)-beta-2, 3 -dideoxy-5-fluoro-3 -thiacytidine in rats, rabbits, dogs, monkeys and HIV-infected humans, Antivir Chem Chemother 16 117-127... 

Nitidine and garonine are known as potential anti-tumour, antileukemic, and antiviral agents [9,52,98]. Some synthetic 12-alkoxyderivatives of 2,3,8,9-tetramethoxy QBA are potent in vitro inhibitors of the growth of P388 cells [144]. Nitidine, isolated firom Kenyan Toddalia aculeata Pers. (synonym T. asiatica (L.) Lamk.) has shown antimalarial activity [145]. Nitidine and fagaronine have been foimd to inhibit HTV reverse transcriptase [146]. 

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