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.
Highlights
The rapid spread of the recently emerging coronavirus disease, COVID-19, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has given rise to the current pneumonia pandemic, which has a moderate (5%) fatality rate compared to SARSCoV-1 (10% fatality rate) and Middle East Respiratory Coronavirus (MERS-CoV) (34% fatality rate), due to sepsis/acute respiratory distress syndrome (SARS) [1,2]
In order to review the nature of coronavirus membrane reorganizations, it is important to note that all nidovirales rearrange host membranes in similar manners, thanks to nsps derived from pp1a and pp1ab
These authors had a different interpretation of their observations, we suggest that the N-terminal transmembrane domain of M may be capable amino acid substitution that allows it to form transmembrane pores, a suggestion that needs to be confirmed or refuted
Summary
The rapid spread of the recently emerging coronavirus disease, COVID-19, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has given rise to the current pneumonia pandemic, which has a moderate (5%) fatality rate compared to SARSCoV-1 (10% fatality rate) and Middle East Respiratory Coronavirus (MERS-CoV) (34% fatality rate), due to sepsis/acute respiratory distress syndrome (SARS) [1,2]. As of 20 November 2020, there have been over 55 million cases, worldwide, with over 12 million (~22%) being within the USA. The disease arose in the city of Wuhan (Hubei Province, China), and seems to have been caused by the sale of live wild animals as a food source in the Wuhan wholefood market [6]. These animals were thought to be the intermediate carrier of the virus, originating in Rhinolophus bats [1]. A greater incidence of the disease in older people, those with co-morbidities such as hypertension and cardiovascular disease, and disproportionate distributions of cases and fatalities among people of different ethnic groups (among African, Hispanic and Native Americans as compared with European Americans) are well established [9,10]
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