Abstract
The new coronavirus disease 2019 (COVID-19) caused by severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) are causing health
crisis of the world. To control the pandemic SARS-CoV-2 infection,
world-wide vaccination is under way. However, no specific therapeutic
drugs are available in the treatment of COVID-19 yet. To find the
effectively therapeutic targets for COVID-19, efforts should be focused
on the pathogenesis of COVID-19. SARS-CoV-2 induced COVID-19 involves
the processes of viral entry into the host cells, viral replication in
the host cells, and induction of cytokine storm and cellular damage.
Therefore, the potential targets may include the structural proteins of
the virus that play roles in the pathogenesis, viral replication
associated enzymes, inflammatory cytokines, and signaling proteins that
mediate the induction of cytokine storm. Further exploring this strategy
may benefit us in finding novel therapeutic targets and effective
treatment of COVID-19.
Key Words: SARS-CoV-2, Cytokine storm, Toll-like receptors,
Janus kinase, NLRP3 inflammasome
INTRODUCTION
Since December 2019, SARS-CoV-2 infection had hit over 134 million
people worldwide with 2.66 million cases of death until the date of
April 6, 2021. SARS-CoV-2 infection not only causes severe respiratory
impairment, but also leads to complications in other systems of the
body, including cardiac and nervous
system, which contribute to the
increased mortality in patients with COVID-19 (Helms et al., 2020; Huang
et al., 2020b; Mao et al., 2020; Thepmankorn et al., 2021). Although the
efforts are underway to control the pandemic with implementation of
vaccination, there is still a lack of specific drugs for the treatment
of COVID-19. However, multiple therapeutic targets have been proposed
and multiple associated therapeutic agents have been tried in the
clinical setting. To explore the pathogenic mechanisms associated with
COVID-19 and thereby find more effectively therapeutic targets are the
urgent task for the control of COVID-19 and reduction of mortality.
The induction of COVID-19 by SARS-CoV-2 infection involve multiple steps
that include viral entry into the host cells, replication of virus, and
induction of pathogenic processes such as cytokine storm. To block
either one of the steps should reduce the severity of infection and
lower the mortality of COVID-19 patients. As a result, targeting these
processes should be an effective strategy to fight against COVID-19. The
review will focus on the following potential target processes and
specific protein targets that are involved in these processes.
VIRAL INVASION
Viral entry into the host cells, such as epithelial cells in respiratory
duct, is the first step for infection. Blockade of the machinery that
mediates cell entry of SARS-CoV-2 can prevent the infection or reduce
the load of the virus and the severity of COVID-19. The following
proteins play important roles in the viral entry into the host cells.