Overview of corona virus PART 1

The overview of CORONA VIRUS :---

• There are 4 types of corona virus :-

1. Alpha coronavirus( bat/ rat)

2. Beta coronavirus (bat /rat)

3. Gamma coronavirus

4. Delta coronavirus

• Disease caused by coronavirus:-

1. Respiratory 

2. enteric 

3. hepatic 

4. neurologic infection{pig,chicken,dog}

•  Humans:-

1.  The coronavirus was thought to cause mild self limiting respiratory infection until 2002 when beta coronavirus cross-species barriers from bats to mammalian host, before jumping to humans, causing SARS.
2.  More recently another beta Coronavirus in response for the serious Middle East respiratory syndrome MERS started in 2012.
3.  The covid-19 is also a beta coronavirus the genome of the virus is fully sequence and appeared to to the most similar to a strain in bat suggesting it also originated from bats.
4. The virus is also very similar to the SARS coronavirus therefore it is  renamed as SARS COV-2
5. It is still not confirmed that the virus jump from bat to human or have a intermediate host (mammalian host)

 

• Structure of the Coronavirus:-

1.  Coronavirus genome is the large single stranded positive sense RNA molecule that contains all information necessary for making of the viral components 

1.        The RNA is coated with the structural protein forming a complex known as the nucleocapsid. 
2.   The nucleocapsid is enclosed in an envelope which is basically a lipidmembrane with embedded protein. 
3.  From the envelope,club- like spikes emanate giving the appearance of the Crown. 
4.   This is where the Corona name came from. 
5.   The integrity of the envelope is essential for viral infection and is the heel of the virus because the lipid membrane can easily destroyed by lipid solvents such as detergents,alcohol and some disinfectants. 
6.   In fact the enveloped virus are the easiest to inactivate when they are outside the host 
7.   In order to infection host cell the Spikes of the virus must bind to the molecule on the cell surface called receptor. 
8.  This binding explains why viruses are usually species specific,they have receptor in some species and not other.

           "No binding =No infection"

•  The virus binds to the receptor which is ACE2 ⇨⇨

•  Infection usually starts with the cells of the respiratory mucosa then it spread to the   epithelial cell of the alveoli in lungs.

         

•   The virus then uses the host machinery to replicate producing virus RNA and protein.

•        These are then assembled into new viral particles called "VIRIONS" by binding into intracellular membrane .

•        The new virions are replaced and the host cell dies 

•        Uncontrolled growth of the virus destroy the respiratory tissue producing symptoms. 

•        Infection triggers the body inflammation response which bring immune cells to the site to fight virus.

•        Well,the inflammation is an important defence mechanism it may become excessive and cause damage to body tissue contributing to the severity of disease.

• Pathogenesis:-

1. Growth of virus destroys respiratory tissue

2. Inflammation also causes damage

• Prognosis :-

1. Healthy people under 60 years 1 to 2% fatality (may require supportive treatment)

2. Elderly or with chronic disease up to 50%fatality,can cause acute pneumonia.

• Binding of SARS COVID 2:--

Que:-  How corona virus enters in our body and infect it??

Ans :-

• In the first step of the receptor binding spike protein is cleaved in to S1 and S2 by the host cell protease main function of S1 is to bind with the host cell surface receptor while S2 function  mediate membrane fusion. 

•  one of the potential therapeutic approaches is to discover a vaccine that either contains antigen derived from the spike protein which can boost recognition of the virus by immune cells to develop monoclonal antibodies that bind to the virus spike protein and block the interaction with the human cell.

• TMPRSS-2. Means (TRANSMEMBRANE PROTEASE SERINE 2) 

•       It is essential for entry and viral spread of coronavirus
  
•       One agent which is currently being tested called camostat mesylate has shown to inhibit TMPRSS-2 and thus consider as potential anti coronavirus candidate
•        The spike has a strong binding affinity to human angiotensin converting enzyme (ACE2) receptor and likely use them as a mechanism for cell entry.
•        The location where ACE2 receptor are highly Expressed is type 2 Alveolar cells ( found in lungs) also found in many extrapulmonary tissues including heart, kidney,endothelium and intestine.
•        So,another potential drug targets could be the interaction sites between ACE2 and spike protein.
•         One compound found which binds with the binding interface of the spike and ace2 complex is the natural flavonoid called herperidin.
•         When there is binding of ace2 and spike protein it causes severe lung injury.
•         This suggests that delivery of excessive solutes form of ACE2 may compitatively binds with SARS COV-2 .
•         This not only neutralize the virus but also reduces cellular ACE 2 which regulate the renin angiotensin to protect the lungs from injury.
•         A small study has already found Recombinant human ACE 2 to the safe with no negative haemodynamic effect in healthy subject.