Therapeutic monoclonal antibodies at phase 3 clinical study for management of Covid-19

Since the emergence of the novel SARS-CoV-2 coronavirus in December 2019, various drugs have been proposed as antiviral agents for treating the coronavirus disease-2019 (COVID-19) patients. Among the very first drugs to be utilized in the clinic were the aminoquinolines chloroquine and hydroxychloroquine (HCQ). At the time this work started, the US FDA and EU EMA had given emergency approval for the use of chloroquine and HCQ in COVID-19 patients. Chloroquine and HCQ have been commonly used for treating malaria and various autoimmune diseases. Additionally, both drugs have been shown to exert other therapeutic effects, including antiviral effects against SARS and MERS causing viruses.  The exact antiviral mode of action of Chloroquine and HCQ is unclear even though these drugs exert a broad range of antiviral effects. HCQ is classically considered as an inhibitor of endocytic pathways through  elevation of endosomal pH, its detailed molecular mechanisms of action as an antiviral compound remains elusive In-vitro studies show that both drugs can block the viral replication of SARS-CoV- 2 in cell cultures, but a high-level assessment suggested that calculated extracellular lung concentrations are well below the in vitro efficacy values and therefore the drug has low potential for in vivo activity at standard dosing regimens.