How Do SARS-CoV-2 antivirals Work?

SARS-C0V-2 antivirals are used to treat coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has led to the global pandemic that started in 2019. SARS-C0V-2 antivirals are novel drugs developed after the outbreak of COVID-19, and some are still under investigation.

SARS-CoV-2 is an RNA virus that spreads through droplets when an infected person talks, coughs, sneezes or laughs. The virus has just one strand of RNA as genetic material, and it uses the host’s cell machinery to grow, replicate and burst out of the cell to infect the other cells.

Currently, there are three SARS-CoV-2 antiviral drugs used to treat COVID-19. The drugs interfere with different enzymes that the virus uses for synthesis of the RNA chain and proteins required for its growth and replication.

Two of the drugs, remdesivir and molnupiravir interfere with the viral RNA-dependent RNA polymerase, the enzyme the virus uses to build RNA chain. The third, nirmatrelvir, interferes with main protease (Mpro), an enzyme required for the synthesis of proteins the virus requires for growth and replication.

Remdesivir

• Remdesivir was the first SARS-C0V-2 antiviral drug to be developed, initially granted Emergency Use Authorization (EUA) in May 2020 and subsequently approved by the FDA in October, 2020. At present, Remdesivir is the only FDA-approved antiviral drug to treat COVID-19, and is infused intravenously.
• Remdesivir is a prodrug that is metabolized in the body into its active form remdesivir triphosphate (RDV-TP). RDV-TP acts like adenosine triphosphate (ATP), the form of energy that cells use, which is also essential for viral RNA replication. RDV-TP gets incorporated into the growing viral RNA chain, preventing its synthesis and replication.

Molnupiravir

• Molnupiravir is still an investigational drug allowed for use under EUA to treat COVID-19. Molnupiravir is metabolized into beta-D-N4-hydroxycytidine (NHC) which acts like cytidine nucleoside, a structural subunit of the RNA. NHC enters the cell, becomes NHC triphosphate (NHC-TP), gets incorporated into the viral DNA and causes errors that accumulate and prevent replication.

Nirmatrelvir-Ritonavir

• Nirmatrelvir has EUA status to treat COVID-19, in combination with ritonavir, an FDA-approved drug used to treat human immunodeficiency virus (HIV) infection. Nirmatrelvir inhibits the main protease (Mpro) that the virus uses to synthesize proteins, preventing its replication. Ritonavir increases nirmatrelvir’s bioavailability by slowing down its metabolism.

SARS-CoV-2 antivirals may be administered as oral tablets, capsules, or intravenous (IV) infusions to treat Coronavirus Disease 2019 (COVID-19).

Side effects of SARS-CoV-2 antivirals may include the following:

• Decrease in estimated glomerular filtration rate (eGFR)
• Decrease in creatinine clearance
• Increase in creatinine levels
• Decrease in hemoglobin levels
• Increase in blood glucose levels
• Decrease in lymphocyte immune cells
• Increase in blood clotting time (prothrombin time)
• Increase in serum levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
• Elevated serum level of lipase, the enzyme that breaks down fats
• Abnormality in platelet count
• Abnormality in levels of leukocyte immune cells
• Nausea
• Diarrhea
• Increase in bilirubin levels
• Generalized seizure
• Skin rash
• Hypersensitivity reactions
• Dizziness
• Taste perversion (dysgeusia)
• High blood pressure (hypertension)
• Muscle pain (myalgia)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of SARS-CoV-2 antivirals include:

• Lagevrio
• molnupiravir
• nirmatrelvir/ritonavir
• Paxlovid
• remdesivir
• Veklury