The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis

Abstract

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of Betacoronavirus that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic Betacoronaviruses include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family. We include information on their structures, functions, and participation in pathogenesis. While the shared proteins among the different coronaviruses may vary in structure and function, they all seem to be multifunctional, a common theme interconnecting these viruses. Many transmembrane proteins encoded within the SARS-CoV-2 genome play important roles in the infection cycle while others have functions yet to be understood. We compare the various structural and nonstructural proteins within the Coronaviridae family to elucidate potential overlaps and parallels in function, focusing primarily on the transmembrane proteins and their influences on host membrane arrangements, secretory pathways, cellular growth inhibition, cell death and immune responses during the viral replication cycle. We also offer bioinformatic analyses of potential viroporin activities of the membrane proteins and their sequence similarities to the Envelope (E) protein. In the last major part of the review, we discuss complement, stimulation of inflammation, and immune evasion/suppression that leads to CoV-derived severe disease and mortality. The overall pathogenesis and disease progression of CoVs is put into perspective by indicating several stages in the resulting infection process in which both host and antiviral therapies could be targeted to block the viral cycle. Lastly, we discuss the development of adaptive immunity against various structural proteins, indicating specific vulnerable regions in the proteins. We discuss current CoV vaccine development approaches with purified proteins, attenuated viruses and DNA vaccines.

SARS-CoV2 infection impairs the metabolism and redox function of cellular glutathione

“…In fact, similarly to other viruses, pathogenic aspects of SARS-CoV2 infection observed at cellular level include an abnormal synthesis and accumulation of viral proteins in the endoplasmic compartment during the earliest phases of virus replication [ 22 ]. SARS-CoV proteins, such as the E protein, may have a direct role in ER stress and in the apoptotic signaling of the infected cell, as well as in the release of the matured virus by the formation of the ER–Golgi intermediate compartment [ 41 , 42 ]. In our study, the ER stress response to SARS-CoV2 infection was demonstrated by PERK expression analysis.…”

Structural basis for SARS-CoV-2 envelope protein recognition of human cell junction protein PALS1

“…1a ). In SARS-CoV-2-infected lung epithelial cells, the replication and transcription of the virus genome produces a high load of the E protein, which localizes to the ERGIC region for viral assembly and budding 12 . It is proposed that the specific interactions between E and PALS1 recruit PALS1 to the site of virus assembly, and could possibly disrupt the polarity complex and vascular structure 4 .…”

The Significance of COVID-19 Immunological Status in Severe Neurological Complications and Multiple Sclerosis—A Literature Review

“…It has been assumed that the early CD4 + and CD8 + response is protective, and if it is not inhibited after a while, the late response is excessive and destructive for the organism [ 21 , 22 ]. It is worth mentioning that the SARS-CoV-2 infection is divided into four phases, of which phase III is characterized by an abnormal inflammatory response, which is associated with systemic complications and extrapulmonary manifestation of the disease that led to phase IV infection, including acute respiratory distress syndrome (ARDS) and multi-organ failure [ 23 , 24 ]. In critically ill patients, a drastic decrease in T-lymphocytes has been noted [ 21 , 25 ].…”