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UniProt release 2020_01

Published February 26, 2020

Headline

Coronavirus SARS-CoV-2 in UniProtKB

At the end of 2019, a novel coronavirus (nCoV) of animal origin started infecting humans, initiating a severe outbreak in China. nCoV infection can result in severe and even fatal respiratory diseases, such as acute respiratory distress syndrome. The virus is highly contagious and transmission occurs via airborne droplets and contact. On January 30th, 2019-nCoV was designated a global health emergency by the WHO. On February 11th, the WHO called the disease caused by the virus COVID-19, and the virus itself was named Severe Acute Respiratory Syndrome-related coronavirus 2 or SARS-CoV-2 by the International Committee on Taxonomy of Viruses (ICTV).

SARS-CoV-2 belongs to the large family of Coronaviridae, genus Betacoronavirus. This genus comprises mainly vertebrate respiratory viruses, including HCoV-OC43, which is responsible for 10% of common colds, and SARS, which caused an epidemic in 2003, resulting in over 8,000 infected individuals in 26 countries. The novel coronavirus genome has been sequenced. Its close similarity to SARS suggests it has emerged from the same reservoir, namely bats.

With a size of 30 kb, coronaviruses have the largest RNA genomes known to date. The genome encodes a polyprotein 1a that can be elongated by ribosomal frameshifting to produce polyprotein 1ab. The short and elongated polyproteins contain 11 and 15 chains, respectively, and are dedicated to viral RNA transcription and replication, while controlling the host antiviral defense. A strategy used by the virus to escape host cell innate immunity is to induce the formation of a specialized intracellular compartment from the endoplasmic reticulum, called endoplasmic spherules, which protects viral dsRNA replication intermediates. Later on subgenomic mRNAs are translated to produce virion structural proteins and yet another set of immune modulatory factors. Virions are assembled at the ER-Golgi intermediate compartment (or ERGIC) and exported out of the cell. The freshly exported virion is not yet infectious. Its surface is covered by spikes, giving the impression a crown (corona in Latin, hence its name), but spike proteins have to be cleaved in order to become functional and to confer infectivity on the virion. The activating proteolytic cleavages occur in the extracellular space.

It is at the level of spike proteins that SARS-CoV-2 diverges from SARS, differing in both amino acid sequence and glycosylation. The SARS-CoV-2 spike protein cleavage site comprises several arginines, making it an excellent substrate for many host proteases. This feature is predicted to enhance virus tropism and virulence. SARS-CoV-2 interacts with the same host receptor as SARS, ACE2, which presumably explains why both viruses infect lungs, as well as the small intestine and kidney. The functions of several other SARS-CoV-2 proteins are still unclear and need further investigations. Among them is SARS-CoV-2 NS8 protein, which shares sequence similarity with some Bat-hosted coronavirus NS8 proteins, but is entirely different from SARS NS8a or NS8b. Thus, in spite of many similarities to SARS and other coronaviruses, SARS-CoV-2 displays unique molecular features that lead to unpredictable behavior during infection.

SARS-CoV-2 protein sequences from the current public health emergency have been annotated in UniProtKB and made available as a pre-release dataset on the UniProt FTP site. These entries will be available in the usual file formats as part of release 2020_02.

UniProt release news

Starting with release 2020_01 of February 26th, UniProt releases are published every 8 weeks. Release 2020_02 is scheduled for April 22nd, 2020.

See also: How frequently is UniProt released? What is the synchronization delay with other databases?

UniProtKB news

Changes to the controlled vocabulary of human diseases

New diseases:

Deleted disease

  • Popov-Chang syndrome

Changes to the controlled vocabulary for PTMs

New term for the feature key 'Modified residue' ('MOD_RES' in the flat file):

  • N6-lactoyllysine

Modified term for the feature key 'Modified residue' ('MOD_RES' in the flat file):

  • 6-(S-cysteinyl)-8alpha-(pros-histidyl)-FAD (Cys-His) -> 6-(S-cysteinyl)-8alpha-(pros-histidyl)-FAD (His-Cys)
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