Information used appropriately can change the world. We highlight the need for simple strategies with corona – in much the same way that humanity has  used simple knowledge and simple strategies to control the complications of cholera infection. High-tech emergency management gives way to low-tech low-cost high efficiency solutions.

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Erasmus Erasmus : Let’s get back to talking about the virus.

 

Dr Xxxxx Dr Xxxxx :  The Coronaviridae family has two subfamilies - Coronavirinae and Torovirinae.


Taxonomic structure of the subfamily: Subfamily Coronavirinae

* Genus   Alpha coronavirus
* Genus   Betacoronavirus
* Genus   Gammacoronavirus
* Genus   Deltacoronavirus

Taxonomic structure of the subfamily: Subfamily Torovirinae

* Genus   Torovirus,
* Genus Bafininivirus

The Corona Virus Family Tree Corona Virus Genetics displayed as a family tree of evolution.

 

 

Common human coronaviruses
* 1. 229E (alpha coronavirus)
* 2. NL63 (alpha coronavirus)
* 3. OC43 (beta coronavirus)
* 4. HKU1 (beta coronavirus)

* Other human coronaviruses
* 5. MERS-CoV (the beta coronavirus that causes Middle East Respiratory Syndrome, or MERS)
* 6. SARS-CoV (the beta coronavirus that causes severe acute respiratory syndrome, or SARS)
* 7. SARS-CoV-2 (the novel coronavirus that causes coronavirus disease 2019, or COVID-19)
People around the world commonly get infected with human coronaviruses 229E, NL63, OC43, and HKU1.

Sometimes coronaviruses that infect animals can evolve and make people sick and become a new human coronavirus. Three recent examples of this are 2019-nCoV, SARS-CoV, and MERS-CoV.

A Human Family Tree Human Family Tree

Erasmus Erasmus : Since these viruses can mutate so much, how can we tell that they are related?

Dr Xxxxx Dr Xxxxx : The replicase polyproteins of the Coronaviridae comprise a number of characteristic domains arranged in a conserved order. Viruses that share more than 90% sequence identity in the conserved replicase domains are considered to belong to the same species. This 90% identity threshold serves as the sole species demarcation criterion.

Dr Xxxxx Dr Xxxxx :  The members of the family Coronaviridae are enveloped and positive stranded RNA viruses. They affect mammals, birds, even fishes.

Enveloped Virus The concept of an "enveloped" virus

An Enveloped Virus

Being an enveloped virus is a fact critically important to its control. Enveloped means that the virus has a lipid coat. This helps hide the virus from the immune system, but makes it very fragile as well.

Target for  IIPI: Intensive Infection Process Intervention
: Any factor affecting the lipid envelope: either of the virus or even of the host cells in the interaction with the virus.

The Viral Lipid Envelop: the enveloped virus
The viral Envelope contains a variable number of viral membrane protein species, two of which seem to be conserved throughout the entire viral family and are essential for virion growth/replication and infectivity.
• A 200- to 250-aa triple-spanning NexoCendo integral membrane protein M
• An extensively N-glycosylated, 1100- to 1600-amino acid class I fusion protein S which forms peplomers.

Coronaviruses acquire their lipid envelopes by budding at membranes of the endoplasmic reticulum, intermediate compartment and/or Golgi complex. The S and E proteins are palmitoylated. These facts provide potential critical intervention targets.

Enveloped Virus The concept of an "enveloped" virus

Erasmus Erasmus : So knowing about the structure and functions of the virus would give us targets for intervention to control viral replication/ infection.
Dr Xxxxx Dr Xxxxx : Just so. So let’s try to summarize a few of these issues.

Target: vaccination and immunity ,the development of antibodies to exposed proteins.

 

Enveloped Virus The concept of an "enveloped" virus with spike proteins prtruding from its structure: hence the name "corona" or crown like covering of spike protein particles.


 

Viral Assembly & Membrane Proteins

Dr Xxxxx Dr Xxxxx :  Morphogenesis: virion assembly occurs through budding of preformed nucleocapsids at smooth intracellular membranes of endoplasmic reticulum/early Golgi compartments. These facts provide critical intervention targets.

Target: there is approximately 60%-70% homology between MP3 the protease of the coronavirus and the protease found in the HIV virus. This means that there is some potential for action by one specific HIV protease, perhaps on the coronavirus protease.

Dr Xxxxx Dr Xxxxx : In terms of genome size and genetic complexity, the Coronaviridae are among the largest RNA viruses identified so far. They are complex constructs. - With many components and proteins. Being a complex virus means that there are many potential targets for medication intervention.

Target: multiple functions and multiple proteins. Potential targets for future research and development.

Dr Xxxxx Dr Xxxxx :  Coronaviruses are so named because of their characteristic solar corona (crown-like) appearance when observed under an electron microscope. This appearance is produced by the peplomers of the spike [S] glycoprotein (large, club- or petal-shaped large (15–20 nm) surface projections) radiating from the virus lipid envelope. Members of the family Coronaviridae all seem to share two envelope protein species, the membrane (M) and spike (S) proteins. The S glycoprotein is a major antigen responsible for both receptor binding and cell membrane fusion and the transmembrane glycoprotein [M] is involved in budding and envelope formation; the M protein has also been found to play a pivotal role in virion assembly.

 

Corona Virus Structure The concept of an "enveloped" virus with spike proteins prtruding from its structure: hence the name "corona" or crown like covering of spike protein particles.

 

A few coronavirus species have a third glycoprotein, the haemagglutinin-esterase [HE]. The viral genome is associated with the basic phosphoprotein [N] within the capsid.

Virions attach to dedicated host cell surface receptors via their spikes and release their genome into the target cell via fusion of the viral envelope with the plasma membrane and/or the limiting membrane of an endocytic vesicle.

 

Dr Xxxxx Dr Xxxxx : All members of the Coronaviridae family also share the following structural characteristics:

Nucleocapsid: helical, comprised of genome and multiple copies of a single basic phosphoprotein species (N). The nucleocapsids are helical and can be released from the virion by treatment with detergents. The susceptibility of the virus to detergent action either by action on the envelope or the nucleocapsid is a critical intervention target.

Target: if detergents can destroy viral structure, it suggests that handwashing is a very effective control strategy.

The nucleocapsid protein N, a 349 to 470 amino acid RNA-binding phosphoprotein. Besides its obvious function in genome encapsidation, the N protein also is involved in RNA synthesis and translation, displays RNA chaperone activity, and acts as a type I interferon antagonist. This is a potential critical intervention target.
This appears to be the viruses’ main trick for success. By suppressing interferon, viral replication can occur for longer. Local infections get worse, last longer, and are harder for the immune system to control.

Viral growth - exponential. Infection> Epidemic

Dr Xxxxx Dr Xxxxx : Corona Virus Genome
Interspersed between the structural protein genes, there may be up to at least eight accessory (also called “group” or “niche-specific”) genes, the products of which are generally dispensable for replication in vitro, but key to efficient replication during natural infection).

Apparently, these accessory genes were acquired through horizontal gene transfer and occasionally also lost again as the different coronaviruses evolved and diverged while adapting to new hosts and niches. The diversity of accessory genes, most of which are specific only to a distinct CoV lineage species or strain (, attest to the plasticity and highly dynamic nature of the coronavirus genome.

 

Target: Possible future Research and Development focus.

Replication
The entire replication cycle takes place in the cytoplasm and involves the production of full-length and subgenome-sized (sg) minus-strand RNA intermediates with the viral genome serving both as mRNA for the replicase polyproteins and as a template for minus-strand synthesis.

Antigen To Antibody Reactions Antigen- Antibody interactions

 

Antigenic Properties
Dr Xxxxx Dr Xxxxx : Antigenic properties
Cross-reactivity among coronaviruses is limited to (closely-related) species within the same genus.

The S protein is the major inducer of virus-neutralizing antibodies that are elicited mainly by epitopes in the amino terminal half of the molecule. The surface-exposed amino-terminus of the M protein induces antibodies that neutralize virus infectivity in the presence of complement.

While the HE protein of group A betacoronaviruses induces antibodies that prevent virion binding to O-acetylated sialic acids or inhibit sialate-O-acetylesterase activity.
The N protein is a dominant antigen during the natural infection and while N-specific antibodies may provide little immune protection, they are of serodiagnostic relevance.

The ectodomains of the S and HE proteins are highly variable, suggestive of extensive antigenic drift. Studies performed with murine and feline coronaviruses indicate that both structural and non-structural (replicase) proteins serve as CD4+ and CD8+ T cell antigens.

There is no serologic cross-reactivity between corona-, toro- and bafiniviruses.