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.