Abstract
An acute respiratory disorder (COVID-19) that accelerated across the globe has been found to be caused by a novel strain of coronaviruses (SARS-CoV-2). The absence of a specific antiviral drug or vaccination has promoted the development of immediate therapeutic responses against SARS-CoV-2. As increased levels of plasma chemokines and, cytokines and an uncontrolled influx of inflammatory cells were observed in lethal cases, it was concluded that the severity of the infection corresponded with the imbalanced host immunity against the virus. Tracing back the knowledge acquired from SERS and MERS infections, clinical evidence suggested similar host immune reactions and host ACE2 receptor-derived invasion by SARS-CoV-2. Further studies revealed the integral role of proteases (TMPRSS2, cathepsins, plasmin, etc.) in viral entry and the immune system. This review aims to provide a brief review on the latest research progress in identifying the potential role of proteases in SARS-CoV-2 viral spread and infection and combines it with already known information on the role of different proteases in providing an immune response. It further proposes a multidisciplinary clinical approach to target proteases specifically, through a combinatorial administration of protease inhibitors. This predictive review may help in providing a perspective to gain deeper insights of the proteolytic web involved in SARS-CoV-2 viral invasion and host immune response.
Highlights
Since early 2020, the world has been experiencing the uncontrollable spread of novel coronavirus (2019-nCOV) dependent acute respiratory illness, the outbreak of which was first reported in the city of Wuhan, Hubei, China in late 2019
This review aims to provide a brief review on the latest research progress in identifying the potential role of proteases in Severe Acute Respiratory Syndrome (SARS)-CoV-2 viral spread and infection and combines it with already known information on the role of different proteases in providing an immune response
This review focuses on gathering recent clinical data on the host immune response and correlating these with our current knowledge about the viruses, providing updates on the application of host cell proteases as a potential therapeutic approach against COVID-19 viral replication, and discussing the severity of disease
Summary
Since early 2020, the world has been experiencing the uncontrollable spread of novel coronavirus (2019-nCOV) dependent acute respiratory illness, the outbreak of which was first reported in the city of Wuhan, Hubei, China in late 2019. Generation sequencing (NGS) revealed a genome sequence similarity between, and distinct genomic composition of, the causative agent of SARSCoV and MERS-CoV, identified in 2002/03 and 2011 respectively, that caused global pandemics of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) (Wu F. et al, 2020). Full-length genome sequences obtained from five patients suffering from an early stage of illness revealed a 79.6% sequence identity to SARS-CoV and 96% identicality at the whole-genome level to a bat coronavirus (Zhou et al, 2020).
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