Small Molecules for the Treatment of Long-COVID-Related Vascular Damage and Abnormal Blood Clotting: A Patent-Based Appraisal

People affected by COVID-19 are exposed to, among others, abnormal clotting and endothelial dysfunction, which may result in deep vein thrombosis, cerebrovascular disorders, and ischemic and non-ischemic heart diseases, to mention a few. Treatments for COVID-19 include antiplatelet (e.g., aspirin, clopidogrel) and anticoagulant agents, but their impact on morbidity and mortality has not been proven. In addition, due to viremia-associated interconnected prothrombotic and proinflammatory events, anti-inflammatory drugs have also been investigated for their ability to mitigate against immune dysregulation due to the cytokine storm. By retrieving patent literature published in the last two years, small molecules patented for long-COVID-related blood clotting and hematological complications are herein examined, along with supporting evidence from preclinical and clinical studies. An overview of the main features and therapeutic potentials of small molecules is provided for the thromboxane receptor antagonist ramatroban, the pan-caspase inhibitor emricasan, and the sodium-hydrogen antiporter 1 (NHE-1) inhibitor rimeporide, as well as natural polyphenolic compounds.