Sunday, September 20, 2020

Proteins encoded by corona virus (SARS-CoV2)

by Swikriti Adhikari, Pratika Regmi, and Sangharshika Chaudhary

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the betacoronavirus of the family Coronaviridae that causes coronavirus disease 2019 (COVID-19). It is an enveloped and bear a non-segmented, positive sense, single-stranded RNA. This 30 kb genome (RNA)  encodes 14 open reading frames, Orfs (Orf is the part of the genetic material that has the ability to be translated). In particular, the 5’ Orf1a / Orf1ab of SARS-CoV-2 encodes for a single polyproteins, which is cleaved by proteolysis of virus’s own protease enzyme and fragmented into 16 non-structural proteins (Nsp1–16) creating the replicase / transcriptase complex (RTC). The proteins encodes by SARS-CoV-2 that are structural proteins, non-structural proteins and accessory proteins.

1. Structural Proteins
Structural viral proteins usually make up the outer coat of the virus and help in packaging of genome. SARS-Cov-2 encodes for four structural proteins and are encoded by the 3’-terminus of the viral genome. These are: 

Spike (S) glycoproteins: It is glycoprotein that gives crown like appearance thus named corona. It represent the largest structures of the virus and are essential for the entry into host cells. S protein attaches to the receptor protein ACE 2 (Angiotensin converting enzyme 2) of host alveoli and facilitate entry. Spike protein together with Hemaglutin esterase (HE) protein assist in entry to the human cell.

Envelope (E) proteins: E protein interacts with membrane protein to form the viral envelope. There is 2 types of  Envelope protein E1 & E2.  E1 is matrix glycoprotein transmembrane protein where as E2 is peplogenic glycoprotein. They are only present in small quantities and most likely function as ion channels, not necessarily needed for viral replication but essential for pathogenesis. 

Membrane/Matrix (M) proteins: They are the most abundant proteins in the virus structure and are responsible for viral membrane curvature and binding to the nucleocapsid.

Nucleocapsid (N) proteins: They bind to the viral RNA genome and ensure the maintenance of the RNA in a ‘beads-on-a-string’ conformation.

   Figure 1: Structural Proteins of SARS-CoV-2 (Picture source: biovendor.com)
  

2. Non-structural Proteins
The non-structural proteins are produced by the 5’-terminal end of the genome. Majority (~66%) segment of viral RNA located in the first ORF translates two polyproteins, pp1a and pp1ab, and encodes 16 non-structural proteins (NSP1-16), while the remaining ORFs encode accessory and structural proteins. The 16 non-structural protein includes;

  1. NSP3: Papain-like protease-Plpro, supplement polyproteins
  2. NSP5: Main protease-Mpro, also called Chymotrypsin-like protease (3CLpro): cuts the polyproteins translated from viral RNA to yield functional viral proteins.
  3. NSP7-8: Primase complex,
  4. NSP12: RNA-dependent RNA polymerase-RdRp
  5. NSP13: Helicase-Hel
  6. NSP14: 3′–5′ Exoribonuclease-ExoN, initiates cap formation
  7. NSP15: Endoribonuclease-NendoU
  8. NSP16: N7- and 2’O-methyltransferases: modify the cap of viral RNAs
  9. other NSPs (1,2,4,6,9,10,11)


Figure 2: Non-structural proteins (upper) and spike protein (lower) encoded by SARS-CoV-2
Picture Source: Viruses 2019, 11(1), 59; https://doi.org/10.3390/v11010059

Nonstructural proteins of corona-viruses and their function

Nonstructural protein (nsp)

functions

nsp1 & 3


Inhibit interferon signaling and block host innate immune response by promotion of cellular degradation and also blocks translation of host’s RNA

nsp2

Binding to proinhibition protein

nsp3 & 5

Promoting cytokine expression and cleavage of viral polyprotein

nsp4 & 6

Contribute to structure of DMVs as transmembrane scaffold protein (DMVs formation)

nsp7/8 complex

Processivity clamp for RNA polymerase by orms hexadecameric complex

nsp9

RNA binding protein phosphatase

nsp10, 16 & 14

Stimulation of ExoN and 2-O-MT activity

nsp12

Replication enzyme (RNA-dependent RNA polymerase)

nsp13

RNA helicase, 5′ triphosphatase

nsp14

Proofreading of viral genome

nsp15

Viral endoribonuclease and chymotrypsin‐like protease

nsp16

Avoiding MDA5 recognition and inhibit innate immunity regulation


3. Accessory Proteins

Apart from structural and non-structural proteins, SARS-CoV-2 encodes a group of unique proteins called accessory proteins. They help to change the environment inside the infected cell to make it easier for the virus to replicate. Many of these accessory proteins have no known homologues. The SARS-CoV-2 genome has an unusually high number of accessory genes in the 3′-end of the genome. The accessory proteins present in SARS-CoV-2 are named under the specific position of the ORFs and they are:

3a protein
3b protein
6 protein
7a protein
7b protein
8a protein
8b protein
9b protein
   

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