Unveiling the Antiviral Potential of Chlorpheniramine Maleate (CPM) Against SARS-CoV-2: Mechanisms and Implications


Since its initial outbreak in Wuhan, China, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound impact on global health and economies.

As researchers scramble to find effective treatments for coronavirus disease 2019 (COVID-19), a multitude of strategies have emerged, including the repurposing of existing drugs with antiviral potential.

Among these agents, antihistamines like Hydroxyzine, Azelastine, Carbinoxamine maleate, and Chlorpheniramine maleate (CPM) have gained attention due to their intriguing ability to combat viral infections.

In particular, CPM, a first-generation H1 antihistamine, has shown promise not only in its conventional use for allergic conditions but also as a potential therapeutic option for COVID-19.

CPM’s Diverse Applications and Anti-Inflammatory Properties

Chlorpheniramine maleate (CPM) has enjoyed a long history as a reliable remedy for various allergic manifestations, such as allergies, hay fever, common cold symptoms, cough, and nasal congestion. The efficacy of CPM can be attributed, in part, to its potent anti-inflammatory and immunomodulatory properties, which extend beyond mere histamine blockade. These attributes underscore its multifaceted role in addressing the symptoms of allergies and viral infections.

Antiviral Potential of CPM: A Brief Overview

In the context of viral infections, CPM’s potential to serve as an antiviral agent has captured researchers’ interest. Early studies revealed its ability to exert antiviral activity against respiratory viruses, including influenza and SARS-CoV-2. This intriguing antiviral effect prompted further investigation into CPM’s mode of action against these pathogens.

CPM’s Mechanism of Antiviral Action: A Puzzle to Solve

While the mechanisms by which antihistamines such as Hydroxyzine exert antiviral effects on SARS-CoV-2 have been partially elucidated, CPM’s modus operandi remains largely enigmatic. Hydroxyzine and related antihistamines have demonstrated their potential to hinder SARS-CoV-2 entry by engaging in off-target inhibitory activities involving ACE2 receptors. These compounds also interact with the sigma-1 receptor, thereby curbing virus replication. However, the precise mechanisms that underpin CPM’s antiviral prowess against SARS-CoV-2 have remained elusive.

Unraveling CPM’s Antiviral Mechanisms: A Step Forward

In light of the gaps in our understanding, researchers have endeavored to unveil the intricacies of CPM’s antiviral mode of action against SARS-CoV-2. By employing cutting-edge molecular and cellular techniques, investigators have embarked on a journey to uncover the precise molecular targets within the viral replication cycle that CPM engages with. This research avenue aims to decipher whether CPM’s antiviral effect stems from its interaction with viral components or if it primarily modulates host factors to inhibit viral replication.

Clinical Insights: CPM’s Promise Against COVID-19

Building upon the foundational research, clinical studies have corroborated CPM’s potential effectiveness in treating COVID-19. The collective data from these studies, spanning various geographical regions and patient populations, support the notion that CPM could be a valuable therapeutic tool in the fight against the pandemic. Reports suggest that CPM not only targets viral replication but also potentially mitigates the excessive inflammatory response associated with severe COVID-19 cases.


The investigation into the potential of Chlorpheniramine maleate (CPM) as an antiviral agent against SARS-CoV-2 has yielded valuable insights into its multifaceted mechanism of action. In this study, we sought to understand how CPM impacts the various stages of the SARS-CoV-2 replication cycle, specifically focusing on viral adsorption, replication, and direct virucidal effects. Our findings reveal the potential of CPM to exert a broad-spectrum antiviral effect through its multitarget action, suggesting its potential utility as a therapeutic agent against COVID-19.

The Impact on Viral Replication Cycle Compartments

Our research unveiled that CPM affects multiple stages of the SARS-CoV-2 replication cycle. It inhibits viral adsorption, thereby preventing the initial binding of the virus to host cells. Additionally, CPM interferes with viral replication within host cells, impeding the virus’s ability to propagate. Notably, the direct virucidal effect of CPM adds to its arsenal of antiviral actions, directly targeting and deactivating viral particles. These findings highlight CPM’s multi-pronged approach in disrupting the SARS-CoV-2 lifecycle.

Chemoinformatic Analysis and Multitarget Effects

Chemoinformatic analysis of CPM further reinforced its potential as an anti-SARS-CoV-2 agent with multitarget effects. The structural similarities between CPM and drugs known for their anti-inflammatory and antiviral effects underscore its potential to act on multiple viral and host factors simultaneously. This multitarget action presents an advantage, as viruses like SARS-CoV-2 often rely on diverse mechanisms for replication and immune evasion.

Clinical Implications and Efficacy

Our study aligns with growing clinical evidence supporting the efficacy of CPM in treating COVID-19. Clinical studies have demonstrated that CPM contributes to improved clinical recovery and reduced hospitalizations in COVID-19 patients. In particular, intranasal administration of CPM has emerged as a promising early intervention strategy, alleviating symptoms and expediting clinical recovery. The ACCROS-I and ACCROS-II studies underscore CPM’s potential to decrease the severity of cases and hospitalization rates, addressing a significant unmet need in the treatment landscape.

Comparison with Existing Therapeutics

Comparing CPM to the FDA-authorized medications Paxlovid and remdesivir, which have encountered challenges in meeting treatment goals, highlights CPM’s potential as an effective intervention. While Paxlovid’s efficacy has been questioned, CPM’s prior clinical evidence and in vitro studies suggest its potential to reduce symptom severity and accelerate recovery. This evidence supports the notion that early intervention with CPM could mitigate the severity of COVID-19 cases and contribute to better outcomes.

Broad-Spectrum Antiviral Effects and Future Directions

CPM’s broad-spectrum antiviral effects extend beyond SARS-CoV-2 and encompass other viruses such as influenza and Ebola. While our study focused on viral targets, the possibility of host-directed effects cannot be discounted. Transcriptomic and proteomic studies should explore these mechanisms in more detail. The diverse antiviral effects of CPM raise the prospect of its utility in addressing a range of viral infections, positioning it as a versatile candidate for future antiviral research.


As the global scientific community grapples with the challenges posed by COVID-19, the quest for effective treatments remains paramount. Among the arsenal of repurposed drugs, Chlorpheniramine maleate (CPM) stands out as a potential antiviral agent with a proven track record in allergic conditions and emerging promise in combating SARS-CoV-2.

The efforts to uncover the intricate mechanisms by which CPM exerts its antiviral effects represent a significant step forward in our battle against the pandemic. With continued research and clinical trials, CPM could emerge as a critical tool in alleviating the burden of COVID-19 and other viral infections.


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