Name: how antiviral drugs stop viral replication
Uploaded: 2026-05-20T14:37:01.259Z
Duration: 1 min 22 s
Channel: JoVE

Antiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis.For example, acyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus types 1 and 2, and varicella-zoster virus.Acyclovir enters the infected cell through passive diffusion. In the cytoplasm, virus-encoded thymidine kinase phosphorylates acyclovir to form acyclovir monophosphate.Then, host kinases convert acyclovir monophosphate step by step into its diphosphate and active triphosphate forms.Acyclovir triphosphate enters the nucleus, where it mimics deoxyguanosine triphosphate and is mistakenly incorporated by viral DNA polymerase into the growing viral DNA strand.Acyclovir triphosphate lacks a 3&#x2032;-hydroxyl group, so it blocks further addition of nucleotides to the DNA strand.This prematurely terminates DNA synthesis. As a result, viral replication is halted.

inibitori nucleosidici antivirali

Antiviral Nucleoside Inhibitors

Inibitori nucleosidici antivirali
Gli inibitori nucleosidici antivirali sono analoghi strutturali dei nucleosidi naturali che interferiscono con la sintesi del DNA o dell&#x27;RNA virale. Questi composti prendono di mira selettivamente le polimerasi virali a causa della loro somiglianza con i nucleosidi dell&#x27;ospite, interrompendo cos&#xEC; la replicazione del genoma virale.
Meccanismo d&#x27;azione dell&#x27;aciclovir
L&#x27;aciclovir &#xE8; un analogo della guanosina con una catena laterale aciclica a tre atomi di carbonio. Prende di mira selettivamente il virus herpes simplex di tipo 1, o HSV-1, il virus herpes simplex di tipo 2, o HSV-2, e il virus varicella-zoster, o VZV. Una volta all&#x27;interno di una cellula infetta, una timidina chinasi codificata dal virus fosforila l&#x27;aciclovir per formare aciclovir monofosfato. Quindi, le chinasi cellulari dell&#x27;ospite lo convertono in sequenza nella forma difosfato e nella forma trifosfato attiva.
L&#x27;aciclovir trifosfato imita la deossiguanosina trifosfato. Nelle cellule infettate dal virus, viene erroneamente incorporato dalla DNA polimerasi virale nel filamento di DNA virale in crescita. Poich&#xE9; &#xE8; privo di un gruppo 3&#x27;-idrossile, non possono essere aggiunti ulteriori nucleotidi, con conseguente terminazione prematura della sintesi del DNA e successiva inibizione della replicazione virale. La sua affinit&#xE0; preferenziale per la DNA polimerasi virale rispetto alla polimerasi dell&#x27;ospite ne aumenta la tossicit&#xE0; selettiva.
Applicazione pi&#xF9; ampia e gestione della resistenza
Vari inibitori nucleosidici, come ganciclovir, zidovudina e ribavirina, bloccano la replicazione virale interferendo con l&#x27;azione degli enzimi virali o inducendo la terminazione della catena. Ganciclovir, un altro analogo della guanosina, &#xE8; comunemente usato contro il citomegalovirus, o CMV. La zidovudina, un analogo della timidina, &#xE8; ampiamente utilizzata nel trattamento dell&#x27;HIV. La ribavirina, un antivirale ad ampio spettro, interrompe la replicazione di diversi virus a RNA attraverso meccanismi quali l&#x27;inibizione della RNA polimerasi virale e l&#x27;induzione della mutagenesi letale.
La combinazione di questi farmaci rende pi&#xF9; difficile per un virus sviluppare resistenza, poich&#xE9; dovrebbe acquisire simultaneamente pi&#xF9; mutazioni per eludere i diversi meccanismi d&#x27;azione. Questa strategia di combinazione &#xE8; un pilastro della terapia antivirale, in particolare nella gestione delle infezioni virali croniche come l&#x27;HIV e l&#x27;epatite C.

Inibitori nucleosidici antivirali

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Inibitori antivirali dei nucleosidi

how antiviral drugs stop viral replication

Antiviral nucleoside inhibitors stop viruses by blocking DNA or RNA synthesis. These drugs are structural analogs, which means they look like natural nucleosides, the building blocks cells use to make genetic material. Because they resemble host nucleosides, they can interfere with viral polymerases and disrupt viral genome replication.

Acyclovir is a guanosine analog with a three-carbon acyclic side chain. It mainly targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV). Inside an infected cell, a virus-encoded thymidine kinase adds the first phosphate group to acyclovir. Host cellular kinases then convert it into the diphosphate and active triphosphate forms.

The active acyclovir triphosphate mimics deoxyguanosine triphosphate. Viral DNA polymerase can mistake it for a normal building block and add it to the growing viral DNA strand. Acyclovir lacks a 3'-hydroxyl group, so no more nucleotides can be added. This causes premature termination of DNA synthesis and blocks viral replication. Acyclovir also has a stronger affinity for viral DNA polymerase than for host polymerase, which helps make it selectively toxic to infected cells.

Other nucleoside inhibitors work in similar ways but are used against different viruses. Ganciclovir is another guanosine analog and is commonly used against cytomegalovirus (CMV). Zidovudine is a thymidine analog and is widely used in HIV treatment. Ribavirin is a broad-spectrum antiviral that can disrupt several RNA viruses by inhibiting viral RNA polymerase and by causing lethal mutagenesis.

Using these drugs in combination can make resistance harder for a virus to develop. A virus would need to gain multiple mutations at the same time to escape the different drug actions. This combination approach is an important part of antiviral therapy, especially for chronic infections such as HIV and hepatitis C.

How Antiviral Drugs Stop Viral Replication

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key terms and concepts

Learn how nucleoside analogs such as acyclovir, ganciclovir, zidovudine, and ribavirin block viral replication and help limit drug resistance.

How Antiviral Drugs Stop Viral Replication | JoVE K12

JoVE Core Microbiology provides an engaging introduction to the microbial world and its influence on health, industry, and the environment. This comprehensive collection covers key concepts such as microbial structure, metabolism, genetics, and ecology. It introduces essential laboratory techniques and microscopy methods through visually engaging animations. Corresponding scientist-in-action videos bridge classroom concepts with real-world research and applications.

microbiology

How Antiviral Drugs Stop Viral Replication

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