COVID-19

What is SARS-CoV-2?

SARS-CoV-2 (COVID-19, 2019-nCoV) is a major public heatlh threat with more than 1,200,000 deaths worldwide. The first stage in the coronavirus life cycle is viral entry where the viral spike protein will bind to a specific cell surface receptor. The spike proteins of SARS-CoV-2, as well as SARS-CoV-1 and NL63 use angiotensin-converting enzyme 2 (ACE2) as a receptor for binding. An antibody for this ACE2 protein has been produced by ProSci Inc. (Catalog No. 3217) that has been shown to function in immunohistochemistry and immunofluorescence experiments in human samples, and western blot experiments in human, mouse, and rat samples.

SARS-CoV-2 (COVID-19) Background

COVID-19 is an acute respiratory disease caused by novel coronavirus SARS-CoV-2  also known as 2019-nCoV. On March 11, 2020, the World Health Organization (WHO) characterized COVID-19 as a pandemic[i]. COVID-19 coronavirus SARS-CoV-2 belongs to the Betacoronavirus genus originating from bats. Betacoronaviruses can infect mammals, are zoonotic pathogens, and can cause severe respiratory disease in humans. Other viruses in this family are SARS coronavirus and MERS coronavirus. COVID-19 (SARS-CoV-2) has approximately 79% sequence identity to SARS-CoV and 50% to MERS-CoV.[ii] In addition, homology modeling shows COVID-19 (SARS-CoV-2)  has a similar receptor-binding domain structure as SARS-CoV which suggests SARS-CoV-2 uses ACE2 receptor in humans for infection.

SARS-CoV-2 (COVID-19, 2019-nCoV) Structure

The structure[iii] of COVID-19 (SARS-CoV-2) consists of the following: a spike protein (S), hemagglutinin-esterease dimer (HE), a membrane glycoprotein (M), an envelope protein (E), a nucleocapsid protein (N), and RNA as seen in the figure below.

Spike protein (S) is heavily glycosylated, utilizes an N-terminal signal sequence to gain access to the ER and mediate attachment to host receptors. It is the largest structure and makes the distinct spikes on the surface of the virus. For SARS-CoV-2, S protein is cleaved by cellular furin-like protease TMPRSS2[iv] into two separate polypeptides S1 and S2. S1 also consists of a receptor binding domain(RBD) which binds to virus receptor ACE2

RNA is the genome of the virus.

Nucleocapsid protein (N) binds to RNA in vitro and is heavily phosphorylated. N proteins binds the viral genome in a beads on a string type conformation. This protein likely helps tether the viral genome to replicase-transcriptase complex (RTC), and subsequently package the encapsulated genome into viral particles.

Envelope protein (E) is found in small quantities in within the virus. It is most likely a transmembrane protein and with ion channel activity. The protein facilitates assembly and release of the virus and has other functions such as ion channel activity. It is not necessary for viral replication but it is for pathogenesis.

Membrane protein (M) is the most abundant structural protein. It does not contain signal sequence and exists as a dimer in the virion. It may have two different conformations to enable it to promote membrane curvature as well as bind to nucleocapsid.

Hemagglutinin-esterase dimer protein (HE) is present in a subset of betacoronaviruses. The protein binds sialic acids on surface glycoproteins. The protein activities are thought to enhance S protein-mediated cell entry and virus spread through the mucosa.

 

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