Three Main Inducers of Alphacoronavirus Infection of Enterocytes: Sialic Acid, Proteases, and Low pH

Abstract

Transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) are similar coronaviruses, causing diseases characterized by vomiting, diarrhea, and death from severe dehydration in piglets. Thus, they have caused huge losses to the swine-breeding industry worldwide. Nowadays, they are easily transmitted among the continents via vehicles, equipment, and cargo. Both viruses establish an infection in porcine enterocytes in the small intestine, and their spike (S) proteins play a key role in the virus-cell binding process under unfavorable conditions when the intestine with a low pH is filled with a thick layer of mucus and proteases. Sialic acid, proteases, and low pH are three main inducers of coronavirus infection. However, the details of how sialic acid and low pH affect virus binding to the host cell are not determined, and the functions of the proteases are unknown. This review emphasizes the role of three factors in the invasion of TGEV and PEDV into porcine enterocytes and offers more insights into Alphacoronavirus infection in the intestinal environment.

Severity Detection for the Coronavirus Disease 2019 (COVID-19) Patients Using a Machine Learning Model Based on the Blood and Urine Tests

“…So it would be interesting to investigate the underlining mechanism of how the serum sodium may induce the COVID-19 severeness. The feature "Urine | PH(Urine)" is the pH level in the urine, and quite a few investigations observed the aberrant pH levels in the body fluid or fecal matter of the coronavirus-infected animals (Raabis et al, 2018;Yuan et al, 2018). Although the urine pH level was not investigated in the coronavirus-infected animals, this may be worth of an investigation.…”

<p>Molecular Basis for Pathogenicity of Human Coronaviruses</p>

“…?? [(α2,3/2,6-linked Sialic acids)] 44,45 Middle Eastern respiratory syndrome coronavirus (MERS-CoV) DPP4 α2,3/2,6-linked Sialic acids 22,26,27 γ-CoVs Avian infectious bronchitis virus (IBV) _ Neu5Ac 9,11,22 Turkey coronavirus (TCoV) 47 _ _ genetic, receptor recognition, and clinical features (Figures 1 and 2). 6,7 Compared to the human representative SARS and MERS-CoVs, SARS-CoV-2 shows superior pathogenicity and inferior clinical outcomes that are addressed to the receptor recognition by the spike protein S and plasma membrane fusion capacity.…”

“…The cleavage at S1/S2 site is dispensable and could be performed before viral particle budding/release by furin protease (as in MERS) in producing cells or after release by a host protease, while the S2ʹ site is pivotal to host entry and is mostly cleaved by host proteases such as TMPRSSII (as in SARS-CoV-2) at the cell surface or Cathepsin in endosome. 8,9 The N-terminal S1 subunit constitutes the globular region and makes up the large receptor-binding subunit of the S protein while the stalk part is made up of the membrane-proximal S2 subunit ( Figure 2B). The N-terminal S1 and C-terminal S2 of the S protein play a similar role in all CoVs, the S1 region is related to receptor binding, and the S2 domain plays a role in the membrane fusion process ( Figure 2C and D).…”

“…However, two genes in human SARS-CoVs showed major variation with civet SARS-CoVs where the first detected variable region was the accessory gene orf8. 9,15,18 On the basis of orf8 variation, the human transmission of SARS-CoV 2002-2003 outbreak was divided into three phases. The early phase was characterized by a limited number of localized cases.…”

“…Herein, the novel pathogen, SARS-CoV-2, has been categorized into the BetaCoronaVirus family (group B), the 7th recognized as a human pathogen, and the 3rd causing a severe clinical syndrome after SARS and MERS-CoV. [3][4][5] Despite the name and some similarities, there are differences between MERS, SARS, and SARS-CoV-2 in Porcine epidemic diarrhoea coronavirus (PEDV) APN Neu5Ac 9 Human coronavirus 229E (HCoV-229E) APN _ 28 Human coronavirus NL63 (HCoV-NL63) ACE2 _ 22 β-CoVs Bat coronavirus (BCoV) _ N-acetyl-9-O-Sialic acids (Neu5,9Ac2) 22,28 Porcine hemagglutinating encephalomyelitis virus (PHEV) _ N-acetyl-9-O-Sialic acids (Neu5,9Ac2) 22,28 Murine hepatitis virus (MHV) 22 CEACAM1 Neu5,9Ac2, Neu4,5Ac2 28 Human coronavirus 4408 (HCoV-4408) _ _…”