Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread
worldwide and caused widespread devastation. In the absence of
definitive therapy, symptomatic management remains the standard of care.
Repurposing of many existing drugs including several anti-viral drugs is
being attempted to tackle the COVID-19 pandemic. However, most of them
have failed to show significant benefit in clinical trials. An
attractive approach may be to target host proteases involved in
SARS-CoV-2 pathogenesis. The priming of the spike (S) protein of the
virus by proteolytic cleavage by the trans-membrane serine protease-2
(TMPRSS2) is necessary for it to bind to its receptor, angiotensin
converting enzyme-2 (ACE2) and subsequently enter the cell. There are
other proteases with varying spatiotemporal locations that may be
important for viral entry and subsequent replication inside the cells,
and these include trypsin, furin and cathepsins. In this report, we
discuss the tentative therapeutic role of inhibitors of TMPRSS2,
cathepsin, trypsin, furin, plasmin, factor X and elastase in infection
caused by SARS-CoV-2. Both available evidence as well as hypotheses are
discussed, with emphasis on drugs which are approved for other
indications such as bromhexine, ammonium chloride, nafamostat, camostat,
tranexamic acid, epsilon amino-caproic acid, chloroquine, ulinastatin,
aprotinin and anticoagulant drugs. Simultaneously, novel compounds being
tested and problems with using these agents are also discussed.