Strategic Approaches to COVID19 Combining Antivirals, ACE2 Modulation, and Immune Therapies

Introduction

The COVID-19 pandemic has pushed the medical community to explore dynamic, multi-pronged treatment strategies beyond standard protocols. In this insightful review by Mohamed SA Mohamed, the author presents a translational immunology perspective, proposing innovative combinations of antiviral drugs, ACE2-focused therapies, and immune modulators to counter SARS-CoV-2 effectively.
Visit https://www.clinvirologyjournal.com for more groundbreaking research in this field.

Understanding the Viral Mechanism and Lung Impact

SARS-CoV-2 primarily infects Pneumocytes II in the lungs by binding to ACE2 receptors. Once inside the cells, it hijacks host machinery to replicate, resulting in:

• Decreased surfactant production
• Alveolar collapse and pulmonary edema
• Severe inflammation and potential cytokine storm, leading to multi-organ failure

The infection’s progression often necessitates advanced respiratory support, including mechanical ventilation or CPAP.

Diagnosis and Transmission Pathways

The virus manifests through symptoms like fever, dry cough, and shortness of breath, with CT thorax playing a key diagnostic role.
PCR and genetic sequencing remain the gold standards for confirmation.

Additionally, since ACE2 is expressed in lungs, GIT, kidneys, and blood vessels, the virus’s effects extend beyond the lungs—emphasizing the need for multi-organ consideration in treatment strategies.

Blocking the Viral Cycle: Antiviral Intervention

A central recommendation involves Remdesivir, shown to improve outcomes in 68% of severely ill patients. Other promising agents include:

• Ciclesonide (anti-inflammatory)
• Lopinavir–Ritonavir + Ribavirin + Interferon-β: This triple combo reduced symptoms and hospital stay duration in a Hong Kong trial.

Read the full study at https://doi.org/10.29328/journal.ijcv.1001018

Immunity Modulation: Balancing the Body’s Response

Active Immunization

Vaccines like the Moderna mRNA candidate showed early success, with neutralizing antibodies in all participants tested.

Passive Immunization

Antibodies from recovered patients can aid critically ill onesespecially where age or comorbidities worsen outcomes.

Controlling Cytokine Storms

CD24Fc, a recombinant fusion protein, inhibits inflammatory cytokines by preventing DAMPs-TLR interaction. It is under Phase II/III trials for COVID-19.

The Role of Mesenchymal Stem Cells (MSCs)

MSCs regulate immune responses through:

• Secretion of IL-10, TGFβ, VEGF
• Suppression of cytokines like IL-8
• Immunomodulation via PGE2, reducing NK cell activity and inflammation

These cells offer promising regenerative and anti-inflammatory benefits in early clinical trials.

ACE2: A Dual-Faced Target

While ACE2 facilitates viral entry, it also offers protective anti-inflammatory roles. Strategies include:

• Recombinant human ACE2 (rh-ACE2) such as GSK2586881, which may slow viral spread and prevent lung injury
• Trials indicate increased Ang1-7 levels and decreased IL-6, reducing inflammation

As noted by the American Thoracic Society, therapeutic strategies should consider maintaining ACE2’s protective signaling while inhibiting its viral entry function.

What About Hydroxychloroquine

Though initially promising, Hydroxychloroquine trials yielded mixed results. Despite its anti-inflammatory and antiviral potential in vitro, its clinical efficacy remains unproven, with potential adverse effects.

Further Reading and Resources

• https://doi.org/10.29328/journal.ijcv.1001018
• Internal Resource: Browse our COVID-19 treatment strategies category
• Homepage Link: Discover more at https://www.clinvirologyjournal.com your portal to virology breakthroughs.

Conclusion & Recommendations

COVID-19 differs significantly from influenza due to its ACE2 interaction, disrupting tissue protection pathways. The author recommends a combination therapy approach that targets multiple phases:

• Antiviral (e.g., Remdesivir)
• ACE2 modulation
• Immune response regulation CD24Fc, MSCs)

These strategies, supported by clinical trials, promise a comprehensive treatment outlook for the future of pandemic response.

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