Host cell penetration inhibitors

Amantadine hydrochloride Rimantadine hydrochloride Figure 7.17 Examples of host cell penetration inhibitors... 

Antibodies against the virus but also amantadine and derivatives, interfere with host cell penetration. There are nucleoside analogues such as aciclovir and ganciclovir, which interfere with DNA synthesis, especially of herpes viruses. Others like zidovudine and didanosine, inhibit reverse transcriptase of retroviruses. Recently a number of non-nucleoside reverse transcriptase inhibitors was developed for the treatment of HIV infections. Foscarnet, a pyrophosphate analogue, inhibits both reverse transcriptase and DNA synthesis. Protease inhibitors, also developed for the treatment of HIV infections, are active during the fifth step of virus replication. They prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new vi-rons. 

The application of two of these inhibitors, N(O-hydroxyphenyl) sulfi-namoyl-tertiobutyl acetate and N(O-aminophenyl) sulfinamoyl-tertiobutyl acetate, to highly resistant wheat leaves infected with an avirulent strain of stem rust resulted in decreased lignification and decreased necrosis of penetrated host cells and concomitantly led to increased fungal development, occasionally even allowing some sporulation to occur (60). 

One of the motive powers for the design of host molecules for nucleotides is their potential utility in chemotherapy. A number of nucleotide analogues exhibit antiviral activity in vitro [73] for example, 2, 3 -dideoxynucleosides are potent chain-terminating inhibitors of HIV reverse transcripase [74]. However, charged and hydrophilic as they are, they can hardly penetrate across cell... 

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