Responding quickly to emerging respiratory viruses, such as SARS-CoV-2 the causative agent of coronavirus disease 2019 (COVID-19) pandemic, is essential to stop uncontrolled spread of these pathogens and mitigate their socio-economic impact globally. This can be achieved through drug repurposing, which tackles inherent time- and resource-consuming processes associated with conventional drug discovery and development. In this review, we examine key preclinical and clinical therapeutic and prophylactic approaches that have been applied for treatment of SARS-CoV-2 infection. We break these strategies down into virus- versus host-targeting and discuss their reported efficacy, advantages, and disadvantages. Importantly, we highlight emerging evidence on application of host serine protease-inhibiting anticoagulants, such as nafamostat mesylate, as a potentially powerful therapy to inhibit virus activation and offer cross-protection against multiple strains of coronavirus, lower inflammatory response independent of its antiviral effect, and modulate clotting problems seen in COVID-19 pneumonia.
【저자키워드】 Drug repurposing, coronavirus, Anti-inflammatory, Antiviral, COVID-19, Coronavirus disease 2019, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, HIV, Human immunodeficiency virus, ACE2, angiotensin-converting enzyme 2, COPD, Chronic obstructive pulmonary disease, SARS-CoV, severe acute respiratory syndrome coronavirus, MERS-CoV, Middle East respiratory syndrome coronavirus, Nafamostat mesylate, Anticoagulant, Ang II, Angiotensin II, RdRp, RNA dependent RNA polymerase, TTSP, type II transmembrane serine protease, VSV, Vesicular stomatitis virus, CoV, coronaviruses, PD-L1, Programmed death-ligand 1, MSC, mesenchymal stem cell, IL6, Interleukin 6, Host-targeting therapies, Mpro, virally encoded main protease of SARS-CoV-2, Nrf2, nuclear factor erythroid 2 p45-related factor 2, IL1B, interleukin 1B, AT1, angiotensin II type 1 receptor, FasL, Fas ligand,