How Does Sofosbuvir Work? Mechanism of Action Explained (Easy)

Sofosbuvir mechanism of action on molecular level reveals how Sovaldi drug treates and cures Hepatitis C. In order to determine the mechanism of action we must understand how the medicine works on preventing Hepatitis C virus, which is destroying one's liver.

Sofosbuvir works by preventing Hepatitic C virus from further replicating. Immune system does the rest.

Hepatitis C virus uses genetic material or RNA to generate new viruses – without RNA, there are no new viruses. In fact when virus infests our liver, billions of virus clones are produced every single day. Our immune system is very efficient at eliminating the viruses, but the magnitude of billions of new virus particles every day is too much and it overwhelms the immune system. Here's where Sofosbuvir comes in to help immune system by decreasing the number of viruses being produced each day.

hep c virus
Billions of Hepatitis C viruses are produced daily in Hep C infested liver

Sovaldi drug prevents the generation of new viral genetic material. This is done by blocking the component that Hepatitis C virus uses to construct genetic material – viral RNA polymerase. Image RNA polymerase as a construction worker that is creating a building – if we eliminate the worker than he will not be able to construct the building. This principle is exactly how Sofosbuvir deals with the virus construction – it inhibits it. The construction is put on hold and immune system comes in like a wrecking ball, smashing the building, or the virus in our case.

Sofosbuvir mechanism of action inhibits viral RNA polymerase by being a defective substrate. Defective substrate is a part of the building that causes the construction halt. This leads to building or virus collapse. Image building the first stage of the building. Then you start using Sofosbuvir – the moment you put the molecule in, the construction cannot continue. In our case, the virus cannot continue to grow – this is the way to fight Hepatitis C virus.

The trick is to convince the virus to take Sofosbuvir inside its structure. If virus knew Sofosbuvir would kill it off, it would never use it. That's why Sofosbuvir has to disguise itself as a useful building block. Virus is using so called nucleosides as a building block. That's why Sofosbuvir disguises itself as a nucleoside.

This mechanism of action is not a new concept. Let us look at a similar molecule called Acyclovir, an antiviral drug.

Hepatitis C virus uses nucleoside such as guanosine seen in the picture to build new viruses. Acyclovir, on the other hand, is a nucleoside analogue and mimics guanosine. However, if virus instead of guanosine uses acyclovir, the acyclovir will prevent virus from replicating. In such a way, the Hepatitis C virus is eliminated from the body by immune system.


Acyclovir is a prodrug and has to be turned on to start the treatment. This is done by attaching a phosphate group to -OH group on acyclovir seen on the picture. This, however, takes some time and here the Sofosbuvir has the advantage.

Now let us look at Sofosbuvir molecule below. The problem with previous antiviral drugs is that the activation step took time and were slow. What Sofosbuvir brings to the table is that it is already activated.

sofosbuvir mechanism of action

As you can see from the molecule, P is already there – the molecule is already activated. In the body, the molecule left of P is separated and Sofosbuvir can go to work. The major advantage of this is that there is no prior activation needed as with other antiviral drugs.

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