Pathophysiology and treatment strategies for COVID-19

Abstract

The outbreak of Coronavirus disease of 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has posed a serious health threat. The increasing number of COVID-19 cases around the world is overwhelming hospitals and pushing the global death toll to over 746,000, which has pushed the sprint to find new treatment options. In this article, we reviewed the SARS-CoV-2 pathophysiology, transmission, and potential treatment strategies.

Keywords: 2019 novel coronavirus; ACE-2 receptor; Pandemic; Receptor binding protein; SARS-CoV-2; Viral inhibitor.

Fig. 1

Taxonomy of Coronaviridae. HCoV, human coronavirus; MERS-CoV, Middle East respiratory syndrome coronavirus; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; SW1, Beluga whale coronavirus; and BuCoV-HKU11, bulbul coronavirus HKU11

Fig. 2

Schematic representation of the SARS-CoV-2 structure, genome and functional domain of SARS-CoV-2 S protein. The viral surface proteins, envelope membrane and spike, are embedded in a lipid bilayer, while the single-stranded positive-sense viral RNA (SS-RNA) is associated with the nucleocapsid protein. The spike proteins contain S1 and S2 subunits and the cleavage sites for furin and TMPRSS2. The spike proteins mediate the viral attachment to the host cells after activation by the enzyme TMPRSS2. SP, signal peptide; NTD, N-terminal domain; RBD, receptor-binding domain, contains core binding motif in the external subdomain; FP, fusion peptide; HR, heptad repeat 1 and heptad repeat 2; TM, transmembrane domain; CP, cytoplasm domain

Fig. 3

An infection and replication model of SARS-CoV-2 in host cells and current treatment strategies to interfere with steps in the SARS-CoV-2 replication cycle. SARS-CoV-2 binds to host cells through the ACE2 receptor, and after endocytosis and subsequent uncoating, the components of SARS-CoV-2 use host cells machinery to produce new viruses. Finally, the SARS-CoV-2 virions are released from the host cell by exocytosis. During this process, the viral replication can be inhibited at different stages by repositioned drugs (highlighted in red). On the other hand, SARS-CoV-2 stimulates the host immune system to release the cytokines and subsequent inflammation and immune-dysfunction through activation or impairment of various immune cells, such, dendritic cells, NK cells, macrophages, and neutrophils. This process can lead to sepsis, septic shock, multiple organ failure, and death. SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; TMPRSS2, transmembrane protease serine 2; NK, natural killer; DC, dendritic cell; IL-1, interleukin-1; IL-6, interleukin-6