PROTEIN COMMUNICATION VIA RNA TRANSLATION IN CORONAVIRUS INFECTED CELLS: ROLE OF ACE-2 PROTEIN and MRNA VACCINES | Adamas University

PROTEIN COMMUNICATION VIA RNA TRANSLATION IN CORONAVIRUS INFECTED CELLS: ROLE OF ACE-2 PROTEIN and MRNA VACCINES

Covid-19, SARS-CoV-2

PROTEIN COMMUNICATION VIA RNA TRANSLATION IN CORONAVIRUS INFECTED CELLS: ROLE OF ACE-2 PROTEIN and MRNA VACCINES

Student Contributor: Anusuya Patra (B.Sc Biotechnology IV sem)

Coronavirus was recognized in mid-1960 and later known to affect humans and a variety of mammals. Since, 2002 two types of coronavirus infecting animals and give risen into humans: Severe Acute Respiratory Syndrome (SARS-CoV) recognized in South China in 2003, & Middle East Respiratory Syndrome (MERS-CoV) identified in Saudi Arabia in 2012. 

The Novel Coronavirus has been identified as Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) identified in Wuhan & responsible for Pneumonia outbreak throughout the world. This outbreak was started in China in 2019; during December & became worldwide in a timeframe of a few months. World Health Organization recognized it as a pandemic on 11th March 2020. So far, more than 200, countries that resulted in above 160,000 deaths as of 19th April 2020. This highly infectious virus spread via respiratory droplets and aerosols when an uninfected person comes with contact with an infected person. Viruses play a crucial role in Covid19 though it’s important to understand the mechanisms of viral mRNA translation via Protein Synthesis. 

PROTEIN STRUCTURE: SCARs-CoV-2 has spherical particles and has proteins called spikes. The viruses are to blame morvic envelope particle (virion) & the RNA in this virus has a single-stranded, positive sense. These viruses are the largest members of the RNA virus with a diameter of around 80-160 nanometer in diameter and genomes range from 21-34 kbs. Coronavirus consists of 5 structural proteins.

  1. S (spike)
  2. N (nucleocapsid)
  3. E (envelop)
  4. M(membrane)
  5. HE (Hemagglutinin Esterase).

The most important and specific proteins are Spike Protein (S) & Hemagglutinin Esterase Protein (HE) and they have covered the outer side of the virus. Both are significantly responsible for attaching, infusing, infecting the particular cells of the body. 

S protein binds with HE protein assists in viral entry to the human cells, and this protein attaches to the receptor protein ACE2, this gives a crown-like appearance, and comes up with a name “Corona”. N protein is a ribonucleoprotein that forms the complex with ribonucleic acid to assists the viral assembly. E protein forms the viral envelope. There are two types of “E protein.” 

E1: is a type of glycoprotein transmembrane protein matrix. 

E2: is a protein that helps in the fusion in human cells. M protein: protein forms a viral envelope. HE protein is a peplomer which has a role in hemagglutination. Communication between viruses and infected lung cells: Once, the virus gets into the respiratory system it loves to attack alveoli. In alveoli, there are two types of pneumocytes. Type 1 pneumocytes: is for gastric exchange.  

Type 2 pneumocytes: culture and expressed the surfactant protein (SP-A, SP-B, & pro-sp-C) at mRNA and protein level it decreases the surfactants in alveoli and collapsed in pressure. S protein binds to a specific receptor on Type 2 pneumocytes, this receptor is known as Angiotensin-converting enzyme-2 (ACE-2). When RNA virus enters into the cell binds enlarge the virus action and engulf the virus taken into the cell, then positive sense RNA comes inside the cytoplasm if the Type 2 pneumocytes, it produces host cell ribosomes and it comes to known as mRNA through the translation process. 

In general virus protein has two receptor binding domain ORBDs, facing downward, and another one facing upwards. These receptor binding domains help viruses to bind and invade human cells. The virus targets human ACE-2 receptor binds with amino acid transporter. The rearrangement of spike proteins that cover the viral surface helps to penetrate the virus cells & these viruses dissolve in the own protein shell & RNA releases bellowed inside the cell. 

Coronavirus hijacks the structure of the cell to reproduce the RNA of the virus takes help the host cells an endoplasmic reticulum (ER) in replicating self and magnification the protein part to make a new virus. Once the hijacked cells go to the Golgi bodies the viral RNA & the proteins in a viral protein shell start packaging.

Cell death is a result when the infection function homeostasis. Single-stranded RNA enhances the production of another enzyme called RNA dependent RNA polymerase; it takes RNA and synthesized RNA and coverts into more copies of single-stranded RNA. There are different types of specific polyproteins also included in the virus cells. 

To make the whole virus structure (like nucleocapsid, specific enzymes, spike proteins), there is a specific enzyme that proteolyzes these polyproteins to individual points to need to make a whole virus structure. So, we have enzymes here specific type of proteinases proteolytically cleave this polyprotein into the different viral components that involved for making into the nucleocapsid, specific enzymes, and spike proteins. 

The cells use RNA dependent RNA polymerase and ribosomes to make a protein, to make the components of the viral protein structure. If we combined all nucleocapsid enzyme spike proteins with single-stranded RNA, it comes out with a whole structure virus. Significance of ACE-2 Protein: Angiotensin released from the liver and this is converted into Angiotensin 1 when it comes to the bloodstream, it gets the lungs to release something known as ACE (Angiotensin Converting Enzyme) this allows the conversion of ACE-1 to ACE-2. 

ACE-2 stimulates sympathetic activity and also stimulates Na2+/Cl- re-absorption and K+ excretion & H2O retention virus from ACE which converts into ACE-2. And in hypertension ACE inhibitors are the first-line drugs. In SCARS-CoV-2 ACE-2 (Angiotensin-converting enzyme 2) is a door from where the cells enter the human body and ACE2 protein have important enzymatic functions influencing blood pressure to the organ. The spike protein interacts with the ACE2 receptor and gets entered into the interior of the human cell and the virus can replicate. Simultaneously the spike protein undergoes in the process of unfolding or refolding. This transformation occurs via coiled-spring that start buried at the core of the spike & the spike hooks reconfigured into the cell and helps to crash virus particles. In this way, the viral genetic material can mediate its way into the unsuspecting cell.

If ACE-2 is decreased then the lungs will be more prone to many viral injuries because the ACE-2 protects the lungs. If ACE-2 inhibitor is activated then there will be more number of dying people from heart failure and the chances of death become two-three folds. Though the tough point is that the ACE-2 protein is very controversial but inhibition of the progression of ACE-1 might be helpful to decrease the level of COVID 19. 

Prevention via ACE-2 and some mRNA vaccines: Human recombinant soluble ACE-2 drug is newly synthesized for the treatment of coronavirus, this drug decodes receptor and connects with the spike proteins envelop of the virus to prevent it from connecting and entering in human cells. Another vaccine is known as the mRNA1273 vaccine stabilizes the mRNA and also encodes for a stable form of SARS-CoV-2 spike proteins. mRNA’s vaccines carry the molecular instruction to make protein. The host body uses to produce viral protein provided via the mRNA vaccine, the mRNA vaccine comes out from synthetic mRNA of the virus & the mRNA vaccines mimic as the natural infection of the virus. 

Advantages of mRNA vaccine: The significant advantage of mRNA vaccines that they can produce pure viral proteins & sometimes saving months or years to standardize and ramp up mass production. 

References:

  • Sarah A. Kopecky-Bromberg, Luis Martinez-Sobrido, and Peter Palese, “7a Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cellular Protein Synthesis and Activates p38 Mitogen-Activated Protein Kinase”, J Virol. 2006 Jan; 80(2): 785–793.
  • The Conversation “What the coronavirus does make to your body that makes it so deadly” National Institute of Allergy and Infectious Diseases, NIH Benjamin Neuman Texas A&M University. Published by April 2 2020.
  • Sanjay Mishra, Robert Carnahan, Coronavirus: A new type of vaccine using RNA could heplp defeat Covid 19 NIAID-RML Vanderbilt University Published by March 26.
  • Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Feb 15,395(10223):497-506.
  • Peter & Jack, Coronavirus-Covid 19 | Viral Structure and Pathogenesis Anatomy Zone Published April 3 2020. 

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