Principles and main therapeutic methods of antiviral therapy
Viruses rely on the enzyme system of the host cell to synthesize nucleic acids and proteins within the host cell under the regulation of the genetic information provided by their genes. Subsequently, the virus assembles into a mature infectious virion in the cytoplasm and is eventually released outside the cell in various ways to infect other cells. Because most viruses lack an independent enzyme system, viral nucleic acids are sometimes integrated into cells, which leads to slow research and development of antiviral medicines.
Strategies to combat viral infection include direct inhibition or killing of viruses, interference with viral adsorption, blocking virus penetration into cells, inhibiting viral biosynthesis, preventing viral release, and enhancing host antiviral capacity. Antiviral medicines achieve their effects primarily by influencing a certain point in the viral replication cycle. In addition, vaccines can also be used for prevention, followed by precautions and isolation. Diseases caused by viruses are often the main infectious diseases of humans, including influenza, common cold, measles, mumps, polio, infectious hepatitis, AIDS, etc., as well as latent infections such as herpetic keratitis and venereal herpes virus.
How do antivirals work?
Instead of killing or inactivating the virus, antiviral medicines inhibit viral replication by interfering with specific stages of the viral life cycle. Antivirals use two approaches: targeting the virus itself or host cytokines. The mechanism of action of medicines targeting viruses includes: (1) virus adsorption/invasion inhibitors, (2) coat inhibitors, (3) inhibition of viral replication, (4) inhibition of viral protein synthesis, (5) inhibition of viral assembly, (6) inhibition of viral release.
Fig.1 Common inhibitory effects of antiviral medicine. (Alsafi Radi, et al., 2022)
Types of antiviral Medicine
Antiviral medicines are divided into the following categories based on the different sites at which they act on viral replication:
DNA polymerase inhibitors
Medicines such as Acyclovir, Valacyclovir, and Ganciclovir are inserted into the viral DNA strand by mimicking the nucleotides required for viral DNA replication, resulting in the termination of DNA strand elongation, inhibiting the function of viral DNA polymerase, and thus preventing viral replication. Acyclovir and valacyclovir are mainly used to treat herpesvirus infections, while ganciclovir are used to treat cytomegalovirus (CMV) infections. However, in more severe cases of side effects, ganciclovir may lead to bone marrow suppression and abnormal liver function.
RNA polymerase inhibitors
Lamivudine and Azvudine inhibit viral replication by inhibiting viral RNA polymerase, interfering with viral RNA synthesis. Lamivudine is mainly used to treat hepatitis B and HIV infection, while Azvudine is a new broad-spectrum antiviral medicine. Side effects are liver damage and lactic acidosis in some cases.
Protease inhibitors
Saquinavir, Ritonavir, and Nelfinavirblock the maturation and reproduction of viral polyprotein precursors by inhibiting the activity of viral proteases. They are mainly used to treat HIV infection. Side effects of this class of medicines include fat redistribution, hepatotoxicity, and hyperlipidemia.
Penetration and uncoating inhibitors
Amantadine inhibit viral replication by interfering with the uncoating process of the virus within the host cell and preventing the release of viral RNA. They are mainly used for the treatment and prevention of influenza A.
Neuraminidase inhibitors
Oseltamivir, Zanamivir, and Peramivir reduce the spread of the virus in the body by inhibiting the neuraminidase of the influenza virus, preventing the release of nascent virus particles from infected cells.
Reverse transcriptase inhibitors
Nucleosides: Lamivudine, and Zidovudine cause strand termination by binding to the active site of viral reverse transcriptase, mimicking nucleotides, and inhibiting the replication of HIV and HBV. Side effects of these medicines include gastrointestinal reactions and bone marrow suppression (e.g., zidovudine).
Non-nucleosides: Nevirapine, and Delavirdine inhibit the activity of reverse transcriptase and prevent HIV replication by directly binding to reverse transcriptase and changing its conformation. Side effects of these medicines include skin rash, hepatotoxicity, and central nervous system symptoms such as dizziness and hallucinations due to efavirenz.
Antiviral vaccines
Although antiviral vaccines are not as in-depth as antiviral medicines, there are still many successful research and development cases. Antiviral vaccines can prevent infection by inducing the immune system to produce an immune response to a specific virus. Its mechanism of action mainly includes:
Attenuated or inactivated virus: This method involves using a virus that has been weakened (attenuated) or completely inactivated. These viruses are processed so that they cannot cause disease, but they still allow the body to recognize their antigens and produce an immune response. Typical examples include the flu vaccine and the rabies vaccine.
Recombinant protein or nucleic acid technology: The development of modern technology has made it possible to use an intact virus for vaccines. Take the mRNA vaccine as an example, it directly encodes the genetic information of the viral protein, and after being injected into the human body, this information instructs the cell to synthesize the antigenic protein of the virus independently. These antigenic proteins are then recognized by the immune system, which induces an immune response in the body. Representatives of this technology include mRNA vaccines against the coronavirus.
Viral vector: This method involves inserting a gene fragment of the target virus into another harmless viral vector and then introducing it into the human body. Vector viruses carry the genetic information of the target virus, and after entering human cells, these cells will express the proteins of the target virus, thereby promoting the body's antibody and cellular immune response against these proteins. For example, adenovirus vector vaccines use this technology to achieve immune protection against the target virus.
Conclusion
In recent years, we have made tremendous progress in understanding the genetic basis and molecular mechanisms of disease. New medicines are already available, and more are in development. However, new infectious diseases caused by viruses like COVID-19 remain a huge challenge. In addition, medicine failure in human trials is also a common problem that needs to be studied and addressed. With the advent of many new technologies, we are expected to achieve exciting results, which will provide greater assistance in the development of new medicines.
BOC Sciences provides professional and customized services to support antiviral research. Through its abundant products and technologies, researchers have access to high-quality raw materials and specialized technical support, significantly improving research efficiency and the quality of results.
Reference
- Alsafi, Radi, et al., Antiviral medicines and their roles in the treatment of coronavirus infection." Antiviral Medicines-Intervention Strategies. IntechOpen 2022.
※ Please kindly note that our services are for research use only.
