Development of an innovative inhaler formulation of Nafamostat Mesilate for the management of COVID-19
Project no. 22174 · Status: Kapanmış · 2020
Summary
<p>Antiviral strategies targeting host systems in viral infections may have both therapeutic and prophylactic potential and may help reduce the development of virus resistance. SARS-CoV-2 infections can be fatal with rapid inappropriate excessive inflammatory response, development of severe pneumonia or acute coronary syndrome. Current antiviral drugs offer little protection against the disease. There is an urgent need for effective drugs in disease management that will provide protection before viral disease occurs or prevent the progression of the disease to severe forms in infected individuals. Nafamostat Mesylate (NM), its intravenous form, is a synthetic serine protease inhibitor used in the treatment of acute inflammatory diseases such as intravascular coagulation, shock and pancreatitis. At the same time, there are in vitro studies showing the suppressive effect of SARS-CoV-2 infection with the ability of NM to inhibit serine protease, which causes the development of airway inflammation. Entry of the virus into the lung airway epithelial cell; It occurs through the trans-membrane serine protease-2 (TMPRSS2) enzyme of the virus spike (S) protein, using the angiotensin converting enzyme-2 (ACE2) binding receptor. With the inhibition of serine protease, the penetration of the virus into the lower airway epithelium and its passage into the systemic circulation can be prevented, and a possible pneumonia or excessive systemic inflammatory response can be suppressed. Within the scope of the study carried out in the industrial partnership of Birgi-Mefar Pharmaceuticals, it was aimed to develop an innovative inhaler formulation of NM in the viral infection management process and to evaluate its <em>in vitro</em> and <em>ex vivo</em> antiviral activities against SARS-CoV-2 and H1N1 viruses.</p>