The Place of Mature Drugs in COVID-19 Era

COVID-19 infection, caused by the SARS-CoV-2 virus, is associated with substantial morbidity and mortality. COVID-19 infection has three distinct phases: 1, early infection phase; 2, pulmonary phase; and 3, the hyperinflammatory phase. Despite a major focus on vaccines and new therapeutics, existing drugs sharing some known mechanistic with this virus, have also gained interest. The potential positioning of three mature innovative drugs, which could be of potential use in this pandemic environment, is discussed in this chapter: OM-85 and calcium dobesilate, and their salt form etamsylate, have revealed anti-viral and anti-inflammatory properties. OM-85, a bacterial extract originating from 21 pathogenic strains isolated from human lungs and indicated for the prevention of recurrent respiratory tract infections, stimulates both innate and adaptive immunity, resulting in non-specific loco-regional immune responses. It has shown anti-viral activity in a number of virus infection models, including influenza H1N1, rhinovirus, and more recently, coronaviruses. It has also shown some immunoregulatory properties. Accordingly, there is a rationale for further investigations on OM-85 to be used as prophylaxis for other respiratory infections and potentially in long-COVID. For calcium dobesilate, currently indicated for the treatment of microvascular diseases while preserving microvascular integrity via antioxidant and anti-inflammatory properties, there are cumulating data that could promote its potential use for the treatment during phase 2 to protect the vascular endothelium. Calcium dobesilate has anti-viral properties and was recently shown to interfere with the SARS-CoV-2 spike-protein binding to the ACE2 receptor. Accordingly, one could also postulate to use it during phase 1. Etamsylate, an anti-haemorrhagic and antiangiogenic agent that improves platelet adhesiveness and restores capillary resistance, is indicated for the prevention and treatment of capillary haemorrhages. Considering its mechanism of action, etamsylate could be envisage for use as potential treatment during phase 3 for viral-induced complications. Importantly, none of these afore mentioned drugs are currently approved for the prevention or treatment of SARS-CoV-2 viral infection. Further, the conduction of well-designed clinical trials is warranted.

Keywords: Angiogenesis, Bacterial Lysate, Calcium Dobesilate, Cell Attachment, Cell Entry, Comorbidities, Coronavirus Disease 2019, COVID-19, Drug Repurposing, Etamsylate, Immune System, Immunotherapy, Inflammation, Infection, OM-85, Respiratory Tract Infection, RTI, SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2, Vascular Endothelium.