Overview of Corona virus PART 2

 Replication of SARS-COVID 2:-

• How corona virus replicate in our body??

Ans:--

   1. Attachment:-

                is the first stage in the infection process in which the phage interacts with specific bacterial surface receptors . Most phages have a narrow host range and may infect one species of bacteria or one strain within a species. This unique recognition can be exploited for targeted treatment of bacterial infection by phage therapy or for phage typing to identify unique bacterial subspecies or strains

 2. penetration:-. 

               The second stage of infection is entry  which occurs through contraction of the tail sheath, which acts like a hypodermic needle to inject the viral genome through the cell wall and membrane. The phage head and remaining components remain outside the bacteria.

  3.Uncoating:--

                The process by which an incoming virus is disassembled in the host cell to release a replication-competent viral genome.

  4.Replication or bio synthesis:--

                 After uncoating,first the genomic RNA of coronavirus acts as an m-RNA for translation of replicase polyprotein 1a {pp1a} and {pp1ab}

                Autoproteolytic cleavage of these polyprotein then produce number of non-structural proteins:-

1.RNA-dependent RNA polymerase

2.Helicase

3.Non-structural protein 3,4 and 6:--

                These Non-structural protein 3,4 and 6 are responsible for anchoring coronavirus replication/transcription complex through recruitment of intracellular endoplasmic reticulum membrane to form double membrane vesicles abbreviated as DMV

                 RNA-dependent RNA Polymerase  {RdRp} and helicase localize double membrane vesicles and drive the production of subgenomic RNA's {sg RNA's}

                  The "N" protein on the other hand bind the viral genomic RNA in cytoplasm to form nucleocapsid.

                  Once the final virion assembly occurs in the intermediate compartment, mature virions are released via smooth-walled vesicles by exocytosis.

                 There are few antiviral drugs that are already on the market that have been reported as potentially effective against coronavirus.

                  One of them is anti-malarial drug called "CHLOROQUINE" which is thought to exert it's antiviral activity in part by increasing the PH in host cells lysosomes,which in turn inhibits hydrolytic activity of protease enzyme that are required for processing of viral glycoprotein during infections.

                 Other drugs are combo of:-

1. Lopinavir {protease inhibitor}
2. Ritonavir  {protease inhibitor.                            And
3. Darunavir {protease inhibitor}
4. Cobicistat {protease inhibitor}

                These interact with proteins required for replication of Corona virus by which the structural and accessory proteins are produced in the next phase of translation

                RNA-dependent RNA -polymerase is a target of investigation drugs such as:-

1.REMDESIVIR

2.FAVIPIRAVIR

                 Preliminary research has shown that both of these agents inhibit RNA-dependent RNA-polymerase and thus might be useful in treatment of early or mid-stage covid disease.

   5.After Biosynthesized:--

                Once synthesized,transmembrane structural proteins "S" "M" and "E" are inserted and folded into endoplasmic reticulum(ER) and then transported to the endoplasmic reticulum-golgi intermediate compartment (ERGIC)

+ss RNA--PROTEIN.

• ATTACK POLICY OF CORONA:-

• Step 1:- the virus binds with ACE2 receptor

• Step 2:- makes into vesicles and comes inside.

• Step 3:- lysosomes binds with virus and acid dissolves in it,RNA is released and comes outside into cytoplasm.The virus binds with the ribosomes and creates protein.

• Below are the vaccine of corona virus which on being tested for treatment:--

         

         1.  MODERNA {NIH} vaccines(based on m-rna)Moderna develops vaccines based on messenger rna to produce viral proteins in the body.Government has bankrolled nearly $1billion

             In partnership with national institutes of health (NIH),they found the vaccine protects monkey's from coronavirus.

              In March the first phase 1 human trails was conducted,later the phase 2 was also carried out.They launched phase 3 trails in july-27th.the final trail will enroll 30000 healthy people at about 89 sites around U.S.

             Genetic vaccines phase-3 trails have started on August 11th govt. Awarded them $1.5billion in exchange of 100 million doses.

             2. Astra-zeneca and Oxford-

Based on chimpanzee adenovirus called "ChAdOxL"In may,the U.S. awarded the project $1.2billion in support.

Their phase 1/2 trails revealed that the vaccine was safe,causing no severe side effects,it raised antibodies.

              The vaccine is in 2/3 phase in England and India and phase 3 trails in Brazil and South Africa 

               Emergency vaccines could be delivered by October.

                The company says the total manufacturing capacity for the vaccine stands at 2 billion doses,SII(serum institute of india) has already produced millions of doses to be used in trails.

              3.  Gamaleya research institute (Sputnik-V) A part of Russian ministry of health launched phase 1 trails in June of vaccine called {gram-covid-VAC Lyo)

It is combination of 2 adenovirus"AD-5 and AD-26, both engineered with a coronavirus gene.

                   On August 11th-the president Putin announced that a Russian health care regulator had approved the vaccine renamed as "SPUTNIK-V" before phase 3 trails

                  Vaccine experts described the move as RISKY.

                   The TASS reported,the Vietnam soon agreed to purchase 50 to 150 million doses.