Acute coronary syndrome (ACS) in patients with SARS-CoV-2 infection represents a critical intersection of viral-induced inflammation and cardiovascular pathology. This review explores the dual mechanisms driving SARS-CoV-2-associated ACS and evaluates emerging therapeutic strategies, including phytomedicine and nanotechnology, to address both viral and cardiovascular complications.
SARS-CoV-2 and ACS Pathogenesis
SARS-CoV-2 infection exacerbates ACS through systemic inflammation, endothelial dysfunction, and plaque destabilization. The virus triggers a cytokine storm, marked by elevated inflammatory biomarkers (e.g., IL-6, C-reactive protein), which promote platelet activation, thrombus formation, and coronary microvascular dysfunction. These processes are amplified by hypoxia and hemodynamic instability, creating a perfect storm for myocardial injury.
ACE2 Receptor: A Double-Edged Sword
The angiotensin-converting enzyme 2 (ACE2) receptor, essential for viral entry, is abundantly expressed in cardiovascular tissues. SARS-CoV-2 binding to ACE2 disrupts the renin-angiotensin system, exacerbating endothelial injury, vasoconstriction, and pro-thrombotic states. This receptor-mediated damage underlies both direct myocardial injury and indirect ischemic events, positioning ACE2 modulation as a therapeutic target.
Myocardial Protective Agents
While ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are debated due to their potential ACE2-upregulating effects, melatonin emerges as a promising adjunct. It enhances nitric oxide bioavailability, stabilizes plaques, and mitigates oxidative stress, offering cardioprotection during viral-induced inflammation.
Herbal Medicine: Bridging Antiviral and Cardioprotective Effects
Traditional Chinese medicine (TCM) demonstrates dual efficacy against SARS-CoV-2 and ACS:
Licorice (Glycyrrhiza spp.): Glycyrrhizic acid inhibits viral replication via NF-κB and MAPK pathways while reducing oxidative damage through Nrf2 activation.
Lianhua Qingwen Granules: This formulation blocks ACE2-S protein binding, suppresses cytokine storms (IL-6, TNF-α), and improves endothelial function.
Astragalus membranaceus and Honeysuckle: These herbs modulate immune responses, inhibit viral entry, and attenuate fibrosis, showcasing synergy in COVID-19 and cardiovascular management.
Non-Herbal Interventions
Peptide fusion inhibitors (e.g., EK1C4) and IL-1 antagonists (anakinra) show promise in reducing thromboembolic events and ACS incidence. Anakinra, in particular, improves survival in severe COVID-19 by curbing hyperinflammation, though its efficacy in advanced respiratory failure remains contentious.
Nanotechnology: Precision in Therapy and Prevention
Nanoparticle platforms revolutionize COVID-19 management:
mRNA Vaccines: Lipid nanoparticles in Pfizer-BioNTech and Moderna vaccines enhance mRNA stability and immunogenicity, achieving >95% efficacy.
Nanoceria (NC): These antioxidant nanoparticles mitigate pulmonary fibrosis and acute respiratory distress syndrome (ARDS) via TGF-β inhibition.
Silver Nanoparticles (AgNPs): AgNPs disrupt viral replication and reduce cytokine storms, though toxicity and biodegradability challenges persist.
Nanocarriers functionalized with ACE2-targeting ligands enable precise delivery of antiviral phytochemicals, enhancing therapeutic specificity.
Future Directions
Key priorities include:
Clinical Trials: Large-scale studies to standardize TCM dosages and validate long-term safety.
Mechanistic Insights: Cryo-EM and molecular docking to elucidate herb-ACE2 interactions.
Nanotech Optimization: Improving nanoparticle targeting and clearance mechanisms.
Multi-Omics Integration: Identifying biomarkers for personalized phytotherapy.
Conclusion
SARS-CoV-2-associated ACS demands integrated strategies addressing viral pathogenesis and cardiovascular injury. Phytomedicine, exemplified by TCM, offers multi-targeted benefits, while nanotechnology enhances drug precision. Despite challenges in nanoparticle toxicity and herb standardization, these approaches herald a new era in managing COVID-19 complications. Bridging traditional wisdom with cutting-edge science could redefine therapeutic paradigms, emphasizing safety, efficacy, and holistic care in post-pandemic cardiology.
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The study was recently published in the Exploratory Research and Hypothesis in Medicine .
Exploratory Research and Hypothesis in Medicine (ERHM) publishes original exploratory research articles and state-of-the-art reviews that focus on novel findings and the most recent scientific advances that support new hypotheses in medicine. The journal accepts a wide range of topics, including innovative diagnostic and therapeutic modalities as well as insightful theories related to the practice of medicine. The exploratory research published in ERHM does not necessarily need to be comprehensive and conclusive, but the study design must be solid, the methodologies must be reliable, the results must be true, and the hypothesis must be rational and justifiable with evidence.
