What is the mechanism of the COVID-19 drug? A look into how treatments fight SARS-CoV-2

October 13, 2025 •

4 min read

Antiviral drugs have played a crucial role in managing the COVID-19 pandemic, significantly contributing to symptom alleviation, severity reduction, and expedited recovery. Understanding what is the mechanism of the COVID-19 drug provides insight into how these therapies interfere with the SARS-CoV-2 life cycle and modulate the body's response.

Quick Summary

COVID-19 drugs use different mechanisms, including inhibiting viral replication with antivirals, modulating the immune system with anti-inflammatory agents, and blocking viral entry with antibodies.

Key Points

Antivirals Target Viral Replication: Drugs like Paxlovid, molnupiravir, and remdesivir directly interfere with the SARS-CoV-2 virus's ability to copy itself inside human cells.
Paxlovid Inhibits Protease Activity: Nirmatrelvir blocks the viral main protease ($M^{pro}$) needed to assemble new viral particles, while ritonavir boosts its effectiveness.
Molnupiravir Causes Viral Mutations: This oral antiviral introduces errors into the virus's genetic material during replication, leading to non-functional viral progeny.
Remdesivir Interrupts RNA Synthesis: Administered intravenously, remdesivir is a nucleoside analog that stalls the viral RNA-dependent RNA polymerase (RdRp), halting viral replication.
Immunomodulators Manage Inflammation: In severe cases, corticosteroids like dexamethasone suppress the body's inflammatory response, which is crucial for preventing severe lung damage and multi-organ failure.
Monoclonal Antibodies Block Entry: Earlier antibody treatments worked by blocking the virus's spike protein from attaching to cells, but many became ineffective as new variants emerged.

The pharmacological approach to treating COVID-19 involves two primary strategies: direct-acting antivirals that target the virus itself, and host-directed therapies that modify the body's immune response to the infection. Each class of medication is effective at different stages of the disease progression. Antivirals are most potent when administered early in the infection cycle to curb viral replication, while immunomodulators are reserved for later, more severe stages when the body's overactive inflammatory response becomes the main threat.

Antivirals: Halting the Viral Life Cycle

Direct-acting antivirals are a cornerstone of COVID-19 treatment. They target specific processes necessary for the SARS-CoV-2 virus to replicate within human cells. This is in contrast to vaccines, which prepare the immune system to recognize and fight the virus proactively.

Paxlovid (Nirmatrelvir/Ritonavir)

Paxlovid is an oral antiviral that consists of two medications working in concert: nirmatrelvir and ritonavir.

Nirmatrelvir is a main protease ($M^{pro}$) inhibitor. The SARS-CoV-2 virus, like all viruses, must replicate to spread. To do this, it produces long protein chains that must be cut into smaller, functional pieces by a viral enzyme called the main protease. Nirmatrelvir binds to and inhibits this protease, preventing the virus from assembling its necessary parts.
Ritonavir is a "booster" that helps nirmatrelvir work more effectively. It is a potent inhibitor of an enzyme in the liver called CYP3A4, which is responsible for breaking down many drugs, including nirmatrelvir. By blocking CYP3A4, ritonavir significantly increases the concentration and prolongs the half-life of nirmatrelvir in the body, allowing it to continue fighting the virus longer.

Lagevrio (Molnupiravir)

Molnupiravir is another orally administered antiviral prodrug. Once inside the body's cells, it is converted into its active form, $\beta$-D-N4-hydroxycytidine (NHC).

Viral Error Induction: The mechanism of molnupiravir is a process known as viral error induction, or "error catastrophe". NHC acts as a nucleoside analog, mimicking the building blocks of RNA. When the viral RNA-dependent RNA polymerase (RdRp) attempts to copy the virus's genetic material, it mistakenly incorporates NHC instead of a correct nucleotide. This incorrect incorporation introduces mutations into the viral RNA.
Resulting Non-Viable Virus: The accumulation of errors during repeated replication cycles eventually leads to a non-functional, replication-incompetent viral genome. This drastically reduces the number of infectious viral particles produced.

Veklury (Remdesivir)

Remdesivir is an intravenous antiviral that was one of the first treatments approved for COVID-19.

RdRp Inhibition: Like molnupiravir, remdesivir targets the viral RNA-dependent RNA polymerase (RdRp). It is also a prodrug that is metabolized into an active nucleoside triphosphate analog.
Delayed Chain Termination: The active form of remdesivir is incorporated into the growing viral RNA chain during replication. However, instead of immediately stopping the process, it acts as a delayed chain terminator, causing the RdRp to stall after adding a few more nucleotides. This effectively halts further RNA synthesis and stops the virus from replicating.

Immunomodulators: Managing the Host Response

For patients with severe COVID-19, the main threat is often not the virus itself but the body's hyper-inflammatory response, known as a "cytokine storm." Immunomodulatory drugs are used in these later stages to manage this overwhelming immune reaction and prevent organ damage.

Corticosteroids (e.g., Dexamethasone)

Anti-inflammatory Action: Dexamethasone is a potent corticosteroid that suppresses the inflammatory response. It reduces the production of pro-inflammatory cytokines, lowers systemic inflammation, and is a life-saving treatment for severely ill, hospitalized COVID-19 patients requiring oxygen or ventilation.

JAK Inhibitors (e.g., Baricitinib)

Inhibition of Signaling Pathway: Baricitinib is a Janus kinase (JAK) inhibitor. JAK proteins are part of a signaling pathway that promotes inflammation. By blocking this pathway, baricitinib helps interrupt the inflammatory cascade that contributes to severe COVID-19.

Monoclonal Antibodies (Historically Relevant)

Early in the pandemic, laboratory-produced monoclonal antibodies (mAbs) were used to treat COVID-19. These therapies have since been phased out due to the virus's evolution.

Viral Entry Blockade: Monoclonal antibodies were designed to mimic the natural antibodies of the immune system. They targeted the spike (S) protein on the surface of the SARS-CoV-2 virus, blocking its ability to bind to the ACE2 receptor on human cells and preventing viral entry.
Limitations with Variants: Due to mutations in the spike protein, which is constantly evolving, many earlier monoclonal antibody treatments became ineffective against newer variants, such as Omicron and its subvariants.

Comparing Key COVID-19 Drug Mechanisms


Feature	Paxlovid (Nirmatrelvir/Ritonavir)	Molnupiravir (Lagevrio)	Remdesivir (Veklury)
Mechanism	Inhibits the main viral protease ($M^{pro}$), halting protein processing and viral assembly. Ritonavir boosts nirmatrelvir levels.	Acts as a nucleoside analog that induces lethal mutations (error catastrophe) in the viral RNA during replication.	Acts as a nucleoside analog that inhibits viral RNA-dependent RNA polymerase (RdRp) through delayed chain termination.
Target	Viral main protease ($M^{pro}$).	Viral RNA-dependent RNA polymerase (RdRp).	Viral RNA-dependent RNA polymerase (RdRp).
Administration	Oral pills, taken at home.	Oral pills, taken at home.	Intravenous (IV) infusion, administered in a healthcare setting.
Typical Use	Non-hospitalized, high-risk individuals with mild-to-moderate COVID-19.	Non-hospitalized adults (18+) with mild-to-moderate COVID-19 when Paxlovid or remdesivir are not suitable.	Hospitalized and some non-hospitalized, high-risk patients with mild-to-moderate COVID-19.

Conclusion

The diverse mechanisms of action of COVID-19 medications provide a multi-pronged approach to treatment. Antivirals like Paxlovid, molnupiravir, and remdesivir target specific viral enzymes to suppress replication early in the infection cycle, minimizing viral load and reducing disease severity. Later in the course of severe disease, immunomodulators like dexamethasone help mitigate the body's overactive inflammatory response. Although once vital, older monoclonal antibody therapies have become obsolete due to the evolution of viral variants. This dynamic pharmacological landscape underscores the importance of ongoing research to stay ahead of the virus and develop new treatment strategies. For up-to-date treatment guidelines, consult trusted health resources like the National Institutes of Health.

Frequently Asked Questions

Antiviral drugs directly target the virus to prevent it from replicating, making them most effective in the early stages of infection. Immunomodulators, on the other hand, manage the body's inflammatory response and are used in later stages for severe cases to prevent organ damage caused by an overactive immune system.

In Paxlovid, ritonavir is used as a booster, not an antiviral itself. It inhibits a liver enzyme called CYP3A4, which slows down the metabolism of nirmatrelvir, the primary antiviral component. This allows nirmatrelvir to remain active in the body longer and at higher concentrations.

The SARS-CoV-2 virus continually mutates, especially its spike protein, which is the target for monoclonal antibodies. Many older mAbs became ineffective against newer, dominant variants like Omicron because the viral mutations prevented the antibodies from binding correctly.

Molnupiravir works by introducing mutations specifically into the viral RNA genome. Studies have looked into the potential for mutagenic effects on host cells, and while there is some concern, the drug's mechanism is targeted toward viral replication. Due to potential risks, molnupiravir is typically only recommended when other treatments are not appropriate.

Remdesivir's mechanism of action targets the viral RNA-dependent RNA polymerase, a part of the virus that is highly conserved and less prone to mutation than the spike protein. Therefore, remdesivir has maintained its effectiveness across different SARS-CoV-2 variant periods.

No, oral antiviral treatments like Paxlovid and molnupiravir are not for pre-exposure or post-exposure prophylaxis. They are intended for treating existing, mild-to-moderate infections in high-risk individuals and must be started within a few days of symptom onset.

Timing is critical because the disease has different phases. Antivirals work best during the early phase when the virus is actively replicating, reducing viral load. In contrast, immunomodulators are used in the later phase to calm the hyper-inflammatory immune response that causes severe disease.