Antiviral drug

Antiviral drug

Subject: Science and Technology

Context: The researchers have analysed viral proteins across 27 coronavirus species and thousands of samples from Covid-19 patients, identifying highly conserved sequences that could make the best drug targets.

Concept:

• Drugs often bind inside “pockets” on proteins that hold the drug snugly, causing it to interfere with the protein’s function.
• Scientists can identify potential drug-binding pockets from the 3D structures of viral proteins.
• The team used a computer algorithm to identify drug-binding pockets in the 3D structures of 15 SARS-CoV-2 proteins.
• The researchers then found corresponding proteins in 27 coronavirus species and compared their sequences in the drug-binding pockets.
• The two most conserved “druggable” sites involved proteins (called nsp13 and nsp12 respectively) that are involved in viral RNA replication and transcription.

Antiviral drug

Antiviral drug, any agent that is used in the treatment of an infectious disease caused by a virus.

Virus and Host cell

• Viruses consist of nucleic acid (either DNA or RNA) and a protein
• Because viruses do not have the enzymes that are needed to manufacture cellular components, they are obligate parasites, which means they must enter a cell for replication to occur.
• The nucleic acid of the virus instructs the host cell to produce viral components, which leads to an infectious virus.
• In some cases, as in herpes infections, the viral nucleic acid may remain in the host cell without causing replication of the virus and damage to the host (viral latency). In other cases, the production of virus by the host cell may cause the death of the cell.
• A major problem in treating some viral diseases is that latent viruses can become activated.

Many factors account for the difficulty in developing antiviral agents.

• The structure of each virus differs, and specific therapy is often unsuccessful because of periodic changes in the antigenic proteins of the virus (antigenic proteins provoke an immune response in the host).
• The need for a host cell to support the multiplication of the virus makes treatment difficult because the agent must be able to inhibit the virus without seriously affecting the host cells.
• Viruses can mutate their protein pockets so that drugs no longer fit.
• But some drug-binding pockets are so essential to the protein’s function that they can’t be mutated, and these sequences are generally conserved over time in the same virus, and in related viruses

An antiviral agent must act at one of five basic steps in the viral replication cycle in order to inhibit the virus:

• attachment and penetration of the virus into the host cell,
• Uncoating of virus (e.g., removal of the protein surface and release of the viral DNA or RNA),
• Synthesis of new viral components by the host cell as directed by the virus DNA,
• Assembly of the components into new virus, and
• Release of the virus from the host cell.