Antivirals

Antivirals medications help the body fight off harmful viruses. The drugs can ease symptoms and shorten the length of a viral infection. Antivirals also lower the risk of getting or spreading viruses that cause herpes and HIV. One approved antiviral treats the coronavirus that causes COVID-19.

• Able to enter the cells infected with a virus
• Interfere with viral nucleic acid synthesis and/or regulation
• Some agents interfere with the virus’ ability to bind with a cell
• Some agents stimulate the body’s immune system

Mechanism of Action (in combination or single action)

• Inhibit viral attachment
• Prevent genetic copying of virus
• Prevent viral protein production, which is vital for the reproduction of the virus.

Diagram on R: Schematic description of the mechanism of the four classes of currently available antiviral drugs: fusion inhibitors (interfere with the binding, fusion or entry of a virion), reverse-transcriptase inhibitors (interfere with the translation of viral RNA into DNA), integrase inhibitors (block the viral enzyme integrase, that inserts the viral genome into the DNA of the host cell), protease inhibitors (block proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles)

What are antivirals?

Antivirals are medications that help your body fight off certain viruses that can cause disease. Antiviral drugs are also preventive. They can protect you from getting viral infections or spreading a virus to others.

What are viruses?

Viruses are tiny (microscopic) infectious agents that grow and multiply only inside living cells of an organism. Viruses have receptors that allow them to attach to healthy (host) cells in your body. Once a virus attaches to and enters a host cell, it can replicate (make copies of itself). The host cell dies, and the virus infects other healthy cells.

Sometimes, viruses remain in a host cell without replicating or damaging it. The virus is still there (which means you could be contagious), but you don’t have symptoms. This latent, or inactive, virus can become active at any time and cause symptoms or be passed on to others. The way viruses spread depends on the type of virus.

Viruses can spread through: modes of viral spread (differs by type of virus):

• Contaminated bodily products like blood, urine, feces (poop), vomit, ejaculate (semen) and saliva.
• Bug bites (transfer of a virus from a bug’s saliva into a person’s blood).
• Skin-on-skin contact, including sex.

How do antiviral medications work?

Antiviral medicines work differently depending on the drug and virus type. Antivirals can:

• Block receptors so viruses can’t bind to and enter healthy cells.
• Boost the immune system, helping it fight off a viral infection.
• Lower the viral load (amount of active virus) in the body.

What do antivirals treat?

Most viruses clear up without antiviral medications. Healthcare providers prescribe antivirals to treat chronic or life-threatening viral infections, including:

• Coronaviruses like COVID-19.
• Ebola.
• Flu, including H1N1 (swine flu).
• Genital herpes.
• Hepatitis B and hepatitis C.
• Human immunodeficiency virus (HIV).

Can antivirals cure viral infections?

Antiviral drugs can ease symptoms and shorten how long you are sick with viral infections like the flu and Ebola. They can rid your body of these viruses.

Viral infections like HIV, hepatitis and herpes are chronic. Antivirals can’t get rid of the virus, which stays in your body. However, antiviral medicines can make the virus latent (inactive) so that you have few, if any, symptoms. Symptoms that develop while you take antivirals may be less severe or go away faster.

Can antivirals prevent the spread of viral infections?

Yes, antiviral drugs can keep you from getting certain viral infections after a suspected or known exposure. For instance, taking specific antivirals:

• During pregnancy lowers the risk of a mother passing HIV to her newborn (babies also receive antiviral medicine after delivery).
• Daily lowers the risk of giving herpes or HIV to others or getting HIV from an infected partner.
• Within 72 hours of a potential HIV exposure can lower the chances of getting infected.
• Within 48 hours of exposure to the flu virus may keep you from getting sick.

How do you take antiviral medications?

Most antivirals are oral drugs that you swallow. But you may also receive antiviral medications as:

· Eyedrops.

· Inhaled powder.

· Injection (shot) into a muscle.

· IV into a vein.

· Topical (skin) ointments or creams.

How long do you need to take antiviral drugs?

Treatment length varies depending on the antiviral drug and viral infection. You may need one dose of an IV drug or a week of oral medicine.

People who have chronic ailments like HIV may take daily antivirals for life. This drug regimen keeps the virus from becoming active. It can prevent the virus from infecting others.

What’s the difference between antibiotics and antivirals?

Antibiotics help the immune system fight off bacterial infections. Bacteria typically reproduce outside of cells, making it easier for medicines to target them. An antibiotic can usually treat many different types of bacterial infections. But the drugs do not affect viruses.

Each antiviral only works against a specific virus. Because viruses inside cells are harder to target, antiviral drugs are more challenging to develop. There are more viruses than antiviral drugs to treat them.

What are the potential side effects of antivirals?

Side effects from antivirals vary depending on the drug type and strength (dosage). You may experience:

• Cough.
• Dry mouth.
• Diarrhea.
• Dizziness.
• Fatigue.
• Headaches.
• Insomnia.
• Joint pain or muscle pain.
• Nausea and vomiting.
• Skin rash.

What is antiviral resistance?

Skipping doses or starting and stopping an antiviral medicine can allow a virus to change/adapt so that the antiviral is no longer effective. This is antiviral resistance. People who take antivirals for extended periods are more prone to antiviral resistance.

Who shouldn’t take antiviral medications?

Antivirals are relatively safe medicines. Children as young as two weeks, as well as pregnant and breastfeeding individuals, can take certain antiviral medications. Guidelines for who shouldn’t take antivirals vary depending on the drug. Your healthcare provider can determine whether an antiviral medicine is safe for you.

What You Should Know About Flu Antiviral Drugs

Can flu be treated?

Yes. There are prescription medications called “antiviral drugs” that can be used to treat flu illness. CDC recommends prompt treatment for people who have flu or suspected flu and who are at higher risk of serious flu complications, such as people with asthma, diabetes (including gestational diabetes), or heart disease.

What are flu antiviral drugs?

Flu antiviral drugs are prescription medicines (pills, liquid, an inhaled powder, or an intravenous solution) that fight against flu viruses in your body. Antiviral drugs are not sold over the counter. You can only get them if you have a prescription from a health care provider. Antiviral drugs are different from antibiotics, which fight against bacterial infections. Antiviral drugs for flu only work to treat flu. Flu antiviral drugs are different than antiviral drugs used to treat other infectious diseases such as COVID-19. Antiviral drugs prescribed to treat COVID-19 are not approved or authorized to treat flu.

What should I do if I think I am sick with flu?

If you get sick with flu, antiviral drugs are a treatment option. Check with your doctor promptly if you are at higher risk of serious flu complications (full list of higher risk factors) and you develop flu symptoms. Flu signs and symptoms can include feeling feverish or having a fever, cough, sore throat, runny or stuffy nose, body aches, headache, chills, and fatigue. However, not everyone with the flu has a fever. Your doctor may prescribe antiviral drugs to treat your flu illness.

Should I still get a flu vaccine?

Yes. Antiviral drugs are not a substitute for getting a flu vaccine. While flu vaccine can vary in how well it works, a flu vaccine is best way to help prevent seasonal flu and its potentially serious complications. Everyone 6 months and older should receive a flu vaccine every year. Antiviral drugs are a second line of defense that can be used to treat flu (including seasonal flu and variant flu viruses) if you get sick.

What are the benefits of antiviral drugs?

When treatment is started within two days of becoming sick with flu symptoms, antiviral drugs can lessen fever and flu symptoms and shorten the time you are sick by about one day. They also may reduce the risk of complications such as ear infections in children, respiratory complications requiring antibiotics, and hospitalization in adults. For people at higher risk of serious flu complications, early treatment with an antiviral drug can mean having milder illness instead of more severe illness that might require a hospital stay. For adults hospitalized with flu illness, some studies have reported that early antiviral treatment can reduce their risk of death.

When should antiviral drugs be taken for treatment?

Antiviral treatment provides the greatest benefit when started soon after flu illness begins. Studies show that flu antiviral drugs work best for treatment when they are started within two days of getting sick. However, starting them later can still be beneficial, especially if the sick person is at higher risk of serious flu complications or is in the hospital with more severe illness.  Follow instructions for taking these drugs. Follow your doctor’s instructions and the dose, frequency, and duration listed on the label instructions for taking these drugs.

How long should antiviral drugs be taken?

To treat flu, oseltamivir or inhaled zanamivir are usually prescribed for five days, while one dose of intravenous peramivir or one dose of oral Baloxavir are usually prescribed.  Oseltamivir treatment is given to hospitalized patients, and some patients might be treated for more than five days.

What are the possible side effects of antiviral drugs?

Side effects vary for each medication. The most common side effects for oseltamivir are nausea and vomiting. Zanamivir can cause bronchospasm, and peramivir can cause diarrhea. Other less common side effects also have been reported. Your health care provider can give you more information about these drugs or you can check the Food and Drug Administration (FDA) website for specific information about antiviral drugs, including the manufacturer’s package insert.

Can children take antiviral drugs?

Yes, though this varies by medication. Oseltamivir is recommended by CDC for treatment of flu in children beginning from birth and the American Academy of Pediatrics (AAP) recommends oseltamivir for treatment of flu in children 2 weeks old or older.

• Oseltamivir is available as an oral suspension for children.
• Zanamivir is approved for early treatment of flu in people 7 years and older, though it is not recommended for use in children with underlying respiratory disease, including asthma and other chronic lung diseases.
• Peramivir is approved for early treatment in people 6 months and older.
• Baloxavir is available in a single dose tablet for children aged 5 years and older. While an oral Baloxavir suspension (liquid) medication is approved by FDA, this product is not available for the 2022-2023 flu season.

If your child’s health care provider prescribes oseltamivir capsules for your child and your child cannot swallow capsules, the prescribed capsules may be opened, mixed with a thick sweetened liquid, and given that way.

Can pregnant people take antiviral drugs?

Yes. Oral oseltamivir is recommended for treatment of pregnant people with flu because compared to other recommended antiviral medications, it has the most studies available to suggest that it is safe and beneficial during pregnancy. Baloxavir is not recommended for pregnant people or while breastfeeding, as there are no available efficacy or safety data.

Who should take antiviral drugs?

It’s very important that flu antiviral drugs are started as soon as possible to treat patients who are hospitalized with flu, people who are very sick with flu but who do not need to be hospitalized, and people who are at higher risk of serious flu complications based on their age or health, if they develop flu symptoms. Although other people with mild illness who are not at higher risk of flu complications may also be treated early with antiviral drugs by their doctor, most people who are otherwise healthy and not at higher risk for flu complications do not need to be treated with antiviral drugs.

Following is a list of all the health and age factors that are known to increase a person’s risk of getting serious complications from flu:

• Asthma
• Neurologic and neurodevelopment conditions
• Blood disorders (such as sickle cell disease)
• Chronic lung disease (such as chronic obstructive pulmonary disease [COPD] and cystic fibrosis)
• Endocrine disorders (such as diabetes mellitus)
• Heart disease (such as congenital heart disease, congestive heart failure and coronary artery disease)
• Kidney disorders
• Liver disorders
• Metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders)
• People who are obese with a body mass index [BMI] of 40 or higher
• People younger than 19 years of age on long-term aspirin- or salicylate-containing medications.
• People with a weakened immune system due to disease (such as people with HIV or AIDS, or some cancers such as leukemia) or medications (such as those receiving chemotherapy or radiation treatment for cancer, or persons with chronic conditions requiring chronic corticosteroids or other drugs that suppress the immune system)

Other people at higher risk from flu:

• Adults 65 years and older
• Children younger than 2 years old¹
• Pregnant women and women up to 2 weeks after the end of pregnancy
• People from certain racial and ethnic minority groups, including non-Hispanic Black, Hispanic or Latino, and American Indian or Alaska Native persons
• People who live in nursing homes and other long-term care facilities
• ¹ Although all children younger than 5 years old are considered at higher risk for serious flu complications, the highest risk is for those younger than 2 years old, with the highest hospitalization and death rates among infants younger than 6 months old.

Select groups of antiviral drugs

Antiherpesvirus drugs

Herpesvirus is the DNA-containing virus that causes such diseases as genital herpes, chickenpox, retinitis, and infectious mononucleosis. After the viral particle attaches to the cell membrane and uncoats, the viral DNA is transferred to the nucleus and transcribed into viral mRNA for the viral proteins. Drugs that are effective against herpesviruses interfere with DNA replication. The nucleoside analogs (acyclovir and ganciclovir) actually mimic the normal nucleoside and block the viral DNA polymerase enzyme, which is important in the formation of DNA. All the nucleoside analogs must be activated by addition of a phosphate group before they have antiviral activity. Some of the agents (acyclovir) are activated by a viral enzyme, so they are specific for the cells that contain viral particles. Other agents (idoxuridine) are activated by cellular enzymes, so these have less specificity. Non-nucleoside inhibitors of herpesvirus replication include foscarnet, which directly inhibits the viral DNA polymerase and thus blocks formation of new viral DNA.

Anti-influenza drugs

Influenza is caused by two groups of RNA-containing viruses, influenza A and influenza B. When the RNA is released into the cell, it is directly replicated and also is used to make protein to form new viral particles. Amantadine and rimantadine are oral drugs that can be used for the prevention and treatment of influenza A, but they have no effect against influenza B viruses. The action of amantadine is to block uncoating of the virus within the cell and thus prevent the release of viral RNA into the host cell. Zanamivir, peramivir, and oseltamivir are active against both influenza A and influenza B. Zanamivir is given by inhalation only, peramivir is given intravenously, and oseltamivir can be given orally. These drugs are inhibitors of neuraminidase, a glycoprotein on the surface of the influenza virus. Inhibition of neuraminidase activity decreases the release of virus from infected cells, increases the formation of viral aggregates, and decreases the spread of the virus through the body. If taken within 30 hours of the onset of influenza, both drugs can shorten the duration of the illness.

Anti-HIV drugs

Human immunodeficiency virus (HIV), the virus that causes AIDS, is a retrovirus. Like other retroviruses, HIV contains reverse transcriptase, an enzyme that converts viral RNA into DNA. This DNA is integrated into the DNA of the host cell, where it replicates. Reverse transcriptase (RT) inhibitors work by blocking the action of reverse transcriptase. There are two groups of RT inhibitors. Nucleoside RT inhibitors (e.g., zidovudine, didanosine, zalcitabine, lamivudine, and stavudine) must be phosphorylated to become active. These drugs mimic the normal nucleosides and block reverse transcriptase. Because the different nucleoside RT inhibitors mimic different purines and pyrimidines, use of two of the drugs in this group is more effective than one alone. The second group of RT inhibitors are the non-nucleoside inhibitors (e.g., delaviridine, efanvirenz, and nevirapine), which do not require activation and, because they act through a different mechanism, exhibit a synergistic inhibition of HIV replication when used with the nucleoside RT inhibitors.

A significant challenge with the use of RT inhibitors is the development of resistance; because HIV replicates continuously at a very high rate, there are many chances for mutation and hence the emergence of a virus resistant to many drugs. To combat the emergence of resistant virus, a class of HIV drugs called nucleotide RT inhibitors (e.g., tenofovir) has been developed. These drugs are “preactivated”; that is, they are already phosphorylated and require less cellular processing. Otherwise, they are similar to nucleoside RT inhibitors and non-nucleoside RT inhibitors.

Protease inhibitors (e.g., ritonavir, saquinavir, and indinavir) block the spread of HIV to uninfected cells by inhibiting the viral enzymes involved in the synthesis of new viral particles. Because they act at a different point in the life cycle of HIV, use of a protease inhibitor with an RT inhibitor suppresses replication better than either drug alone. Protease inhibitors also slow the emergence of resistant virus. The principal adverse effects of protease inhibitors are nausea and diarrhea. Long-term use can bring on a syndrome known as lipodystrophy (wasting of peripheral fat, accumulation of central fat, hyperlipidemia, and insulin resistance).

Another class of HIV drugs is the fusion inhibitors (e.g., enfuvirtide). Fusion inhibitors work by blocking the HIV virus from entering human cells. Serious side effects include allergic reactions and infections at sites where the medicine is given intravenously.

Other types of drugs designed to combat HIV include CCR5 antagonists and post-attachment inhibitors, which block different types of molecules on the immune cell surface to prevent HIV from entering the cells, and integrase inhibitors, which block the ability of HIV to replicate. Pharmacokinetic enhancers, although not antiviral drugs themselves, may be used to augment the effectiveness of anti-HIV drugs.

Anti-RSV drugs
Respiratory syncytial virus (RSV) causes a potentially fatal lower respiratory disease in children. The only pharmacological therapy available for treatment of the infection is the nucleoside analogue ribavirin, which can be administered orally, parenterally, or by inhalation. Ribavirin must also be activated by phosphorylation in order to be effective. An injectable humanized monoclonal antibody is available for prevention of RSV infection in high-risk infants and children. It provides passive immunity and must by given by intramuscular injection once a month during RSV season.

Interferons

Interferons represent a group of nonspecific anti-viral proteins produced by host cells in response to viral infections as well as in response to the injection of double-stranded RNA, some protozoal and bacterial components, and other chemical substances. Interferon results in the production of a protein that prevents the synthesis of viral components from the viral nucleic acid template. The interferons are of interest because they have broad-spectrum anti-viral activity and because they inhibit the growth of cancer tissue. However, the use of interferon is limited by adverse effects, a relative lack of efficacy, and the requirement for local or intravenous administration.