SARS-CoV-2- Infection, ACE-2 gene, herd immunity, vaccines

Last Updated on May 20, 2020 by Sagar Aryal

SARS-CoV-2 and COVID-19

Image created using biorender.com

Type of coronavirus strains

There are seven strains of coronavirus

  • Human Coronavirus 229E (HCoV-229E)
  • Human Coronavirus NL63 (HCoV-NL63, New Haven Corona Virus)
  • Human Coronavirus OC43(HCoV-OC43)
  • Human Coronavirus HKU1
  • Middle East Respiratory Syndrome Related Coronavirus (MERS-CoV) previously known as novel coronavirus 2012 & HCoV-EMC
  • Severe Acute Respiratory Syndrome Coronavirus, previously known as SARS CoV, or SARS Classic
  • Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), previously known as 2019-nCoV, or “novel Coronavirus-2019”

How SARS-CoV-2 infect humans?

Host ACE-2 protein act as a receptor for this virus, ACE-2 protein recognizes receptor binding domain on virus spike protein. After recognition and attachment, the virus may enter into the host cell via two types of pathways.

The first pathway SARS CoV-2 follow to enter the host cell is endocytosis and uptake of the virus in endosomes. Host’s pH dependent cysteine protease cathepsin L. cleave the receptor attached spike protein when this receptor attached spike protein gets activated introduce a conformational change and the later fusion of viral envelope with the endosomes will occur.

In the second mechanism, the SARS CoV-2 can enter the host cell directly by proteolytic cleavage of the receptor attached spike protein by the host’s TMPRSS2 or TMPRSS11D serine protease activation of C-terminal part of the spike protein triggers the fusion of the viral envelope with the host cell membrane by introducing conformation change.

After entry translation, as well as replication of viral genome takes place, and these particles assemble into several new viruses & librated by exocytosis to infect more cells. The librated virus can infect a new cell as well as new people.

Role of the high frequency of ACE-2 gene & homozygosity in prevention of infection

In some research it’s found that populations with a high frequency of ACE-2 genes are less susceptible to SARS CoV-2, in a recently reported study, overexpression of ACE2 has been reported to have an overall protective role in viral infection among patients, increase density on the cell surface has been helpful to protect from lung injury. It is observed and analyses that higher expression of the ACE2 gene may promote ACE2 homo-dimerization decrease binding affinity to SARS-CoV-2 RBD as well as masking TMPRSS2 cleavage site.

In some research and analysis, it’s also found that infection and death rate in male is about 1.4-2 times more than female. It is firstly seen in China where infection & death rate in the female is 1.7, and in males is 2.8 this observation is found in several other countries like Germany, France, Italy, and now in India also. Gene for ACE-2 located on X chromosomes and female are homozygous for X chromosomes having a high frequency of ACE2 than male, with several other reasons it’s also a reason females are less susceptible to SARS CoV-2

In some studies, it is found that host susceptibility in South Asians to the SARS CoV-2 will be more similar to East / Southeast Asians rather than the Europeans.

Concept of herd immunity

The immunity produced after the infection is acquired immunity, if more than 50% individuals of a population develop immunity against this virus, rate of infection decrease and can be a break of virus chains, is called as herd immunity. Herd immunity can develop with direct exposure to a virus which risky at this time to expose the population to the virus. The 2nd way to produce herd immunity is vaccination, but at the present time, no particular vaccine against corona is produced. There are several challenges in vaccine production and development of herd immunity

The vaccine against SARS CoV-2 virus and challenges in its production

Viruses are highly mutating, they can change their genome due to lack of proofreading activity during replication of its genome. Unlike bacteria, no permanent vaccine can be produced against viruses due to their changing ability. However, plasma therapy is applicable to the treatment of patient.

We have to develop legend which can alter the binding site of ACE2 to SARS CoV-2, a competitive inhibitor of binding can be also helpful, we have to focus on this. We have to produce a DNA vaccine against coronavirus, a gene that can produce antibodies (protein) against corona and give lifetime protection against this virus.

But there are more challenges to overcome for antibody production and trail which can take several times, and have to over-come several ethical issues. For vaccine production, exposure to the virus is risky due to its high infection and death rate

Plasma therapy

The person who is recovered from COVID-19 develops an antibody against it, plasma obtained from the person blood having antibody is injected in infected person to over-come it, is called plasma therapy. Plasma is obtained from the blood of a person who is recovered from corona and does not have any type of other infectious and blood born disease and injected into an infected person to deliver antibodies for treatment.

Reference

  1. Biotekzone.blogspot.com
  2. Most frequent South Asian haplotypes of ACE2 share identity by descent with East Eurasian population; Anshika Shrivastava, Rudra Kumar Pandey, et all
  3. ACE2 Homo-dimerization, Human Genomic variants and Interaction of Host Protein explain High Population-specific Differences in Outcomes of COVID19; Swarkar Sharma et al.

Internet Sources

  • 6% – https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus
  • 3% – https://en.wikipedia.org/wiki/SARSr-CoV
  • 2% – https://www.researchgate.net/publication/320413912_DnaSP_6_DNA_Sequence_Polymorphism_Analysis_of_Large_Datasets
  • 2% – https://sciencemonk.com/everything-you-need-to-know-about-coronavirus-ncov-2019/
  • 1% – https://www.sciencedirect.com/science/article/pii/S1471490620300570
  • 1% – https://www.researchgate.net/publication/51652847_Old_World_Arenaviruses_Enter_the_Host_Cell_via_the_Multivesicular_Body_and_Depend_on_the_Endosomal_Sorting_Complex_Required_for_Transport
  • 1% – https://www.precisionvaccinations.com/vaccines/coronavirus-vaccines
  • 1% – https://www.nytimes.com/2020/04/24/smarter-living/coronavirus-convalescent-plasma-antibodies.html
  • 1% – https://www.ncbi.nlm.nih.gov/gene/59272
  • 1% – https://www.dhakatribune.com/health/coronavirus/2020/04/18/bangladesh-to-explore-plasma-therapy-for-covid-19
  • 1% – https://cardiooncology.onlinejacc.org/content/early/2020/05/12/j.jaccao.2020.03.001
  • <1% – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699340/
  • <1% – https://hub.jhu.edu/2020/03/13/covid-19-antibody-sera-arturo-casadevall/

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