SARS-CoV

SARS coronavirus (SARS-CoV) is thought to be an animal virus from an as-yet-uncertain animal reservoir, perhaps bats, that spread to other animals (civet cats). The genome of SARS-CoV consists of a single, positive-strand RNA that is approximately 29,700 nucleotides long. The overall genome organization of SARS-CoV is similar to that of other coronaviruses. The reference genome includes 13 genes, which encode at least 14 proteins. Two large overlapping reading frames (ORFs) encompass 71% of the genome. The remainder has 12 potential ORFs, including genes for structural proteins S (spike), E (small envelope), M (membrane), and N (nucleocapsid). Other potential ORFs code for unique putative SARS-CoV-specific polypeptides that lack obvious sequence similarity to known proteins.

1093070-14-4
PLpro inhibitor
1093070-14-4

Background


An overview of SARS-CoV

The SARS virus is a variant of the coronavirus, a pathogen causing atypical pneumonia. The mutant coronavirus is related to influenza virus, but it is a very unique coronavirus. SARS-CoV is a single-stranded RNA virus with about 29,727 nucleotides long, and there are four major open reading frames downstream of the rep gene that encode the structural proteins of all four coronaviruses, S, E, M and N.

The structure of SARS-CoV

SARS-CoV particles are irregular in shape with a diameter of about 60-220nm. There are three glycoproteins on the surface of the membrane:Spike glycoprotein、Envelope Protein、Membrane Protein. The nucleic acid of SARS-CoV is non-segmental single-stranded (+) RNA, with a length of 27-31kb, which is the longest RNA nucleic acid chain in the RNA virus. It has the important structural characteristics of plus strand RNA. This structure is very similar to eukaryotic mRNA, and is an important structural basis for the genome RNA itself to play the role of translation template, which eliminates the transcriptional process of RNA-DNA-RNA. The recombinant rate between the RNA and RNA of SARS virus is very high, and the mutation rate of SARS virus is precise because of this high recombination rate.

The inhibitor of SARS-CoV

6-Thioguanine is an anti-leukemia and immunosuppressant inhibitor, which is an inhibitor of SARS and MERS coronavirus papain (PLpros), and can effectively inhibit the activity of USP2. The value of IC 50 is 25μM and 40μM.

PLpro inhibitor is a potent inhibitor against the papain-like protease (PLpro) from the coronavirus that causes severe acute respiratory syndrome (SARS-CoV).

Remdesivir is a nucleoside analogue, with effective antiviral activity, with EC50s of 74 nM for ARS-CoV and MERS-CoV in HAE cells, and 30 nM for murine hepatitis virus in delayed brain tumor cells.

SARS-CoV and disease

N protein is the most important structural protein of SARS-CoV, located at the core of SARS-CoV. Therefore, the study of N protein is of great significance to the immunization and treatment of SARS. Clinical trials have shown that N protein is widely distributed in many organs and tissues of SARS patients, and its genome sequence is basically conservative, with good antigenicity, early antibody production and strong and lasting immune response. Therefore, N protein can be a candidate gene for SARS vaccine.

References:

1. Peiris, J. S. M., Lai, S. T., Poon, L. L. M., Guan, Y., Yam, L. Y. C., Lim, W., ... & Cheng, V. C. C. (2003). Coronavirus as a possible cause of severe acute respiratory syndrome. The Lancet, 36 1 (9366), 1319-1325.

2. Stavrinides, J., & Guttman, D. S. (2004). Mosaic evolution of the severe acute respiratory syndrome coronavirus. Journal of virology, 78 (1), 76-82.