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COVID 19 : A structural insight.

       Understand the problem, give it a thought ..and act accordingly to find a solution towards it..


This holds very much true in case of the recent 
pandemic COVID-19.What started off as a unusual respiratory  infection, in late 2019 reported from Wuhan,China..has come on to affect 2,627,630 to date. The source of the infection identified as a novel coronavirus has emerged related to Severe Acute Respiratory Syndrome ( SARS ).  
                                                                              
Similar to other coronaviruses, SARS-CoV-2 particles have a spherical structure and have proteins which have spike like structure protruding from their surfaces. Mechanism of action involves the protein spike like structures attach onto human cells, then undergo a structural changes that enables the viral membrane to fuse. And similar to any other virus, this new configuration enables the viruses to multiply. These spikes bind to receptors on the human cell surface called angiotensin-converting enzyme 2 ( ACE2 ).

Cryo electron microscopy method was used to image these biological molecules ( Zhou et al, 2020). The researchers found that the bond between SARS-CoV2 and ACE2 has a profound similarity to the pattern of virus that had caused the 2003 SARS outbreak. However, the difference lies with the amino acids which bind these two molecules. The importance of these bonds and the difference in the structural configuration somehow impacts its transmission. Although SARS causing viruses focused on upper respiratory tract infections, the SARS-CoV2 shows its lethal power by interaction with other receptor cells as well.



The very structural configuration of SARS-CoV 2 and its interaction with the human cells project the key and lock which needs to be understood for anti-viral drugs production. As most anti-virals focus on halting this very interaction, so that targeted viral entry can be avoided. 



SARS-CoV-2 spike proteinAtomic-level structure of the SARS-CoV-2 spike protein. The receptor binding domain, the part of the spike that binds to the host cell, is colored green. UT Austin, McLellan Lab


PiCo Vacc ?


A study funded by NIH's National Institute of Allergy and Infectious Diseases (NIAID) published the atomic- level structure of the SARS- CoV 2. It was found the SARS- CoV 2 spike was 10-20 times more likely to bind ACE2 on human cells than the spike from the SARS virus from 2002. Which might be a potential cause for its easier spread than the earlier virus.

It was also reported that antibodies used for 2002 SARS could not successfully bind to the SARS-CoV 2 spike proteins, suggesting a more targeted study for the potential vaccine and antibody-based strategy which has to be unique to the new structural configuration of the virus.

What seems to be a recent advancement towards the drug discovery against this novel virus, which has led to potential disruption of the mankind comes in the form of a inactivated vaccine PiCo Vacc putforth by  Qiang Gao et al, 2020. The authors concluded that a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology.



Use of convalescent plasma? Antiviral drug/steroid ?


With novel coronavirus, the degree of illness varies, ranging from asymptomatic to fulminant and fatal. What seems to be the way in regards to this illness, involves sepsis, acute respiratory distress syndrome (ARDS), and/or multiple organ failure which are not unique to coronavirus.
 This host response to infection has been well described and involves a complex interaction of cytokine storm, inflammation, endothelial dysfunction, and pathologic coagulation.

The pathway is common to multiple inciting events and has been the target of treatment for years, with therapeutic plasma exchange uniquely offering benefit on multiple levels by removing inflammatory cytokines, stabilizing endothelial membranes, and resetting the hypercoagulable state. 
Convalescent plasma therapy for SARS-CoV-2 has been brought into effect considering the effectiveness of plasma therapy.

THERE IS NO SINGLE ANSWER RATHER A COMPLEX SYNERGISTIC EFFECT MIGHT BE FRUITFUL..

The targets of COVID-19 treatment should be largely divided into two categories. First, it is aimed at the virus itself. The first thing you can think of is destroying the body of the virus. However, destroying the virus itself is a concept of disinfection and is too dangerous for humans to apply. As a therapeutic agent, there are drugs that inhibit RNA-dependent RNA polymerase by inhibiting the replication of viruses (e.g., remdesivir), or drugs that inhibit protease (e.g., lopinavir/ritonavir).





Another target is angiotensin converting enzyme 2 (ACE2), a gatekeeper and receptor for viruses to enter human cells. By raising the intracellular pH, glycosylation of ACE2 can be prevented to block the entry of the virus (e.g., chloroquine) or it can be prevented from binding to ACE2 in advance by sticking to the spike protein of the virus.

Considering the above treatment mechanisms, it can be seen that it is difficult to succeed with only one mechanism to treat COVID-19. Blocking a virus with antibodies is not enough to win the battle. We must also suppress the replication of the virus, and prepare for a cytokine storm that occurs during treatment.

 In conclusion, it makes no sense as to which of these treatment methods was a decisive factor in the successful treatment. Rather, it is necessary to combine all of these to engage in treatment.


It’s hard for people to focus on other people’s problems when we have our own fears — that’s human nature — but that’s exactly the opportunity to show human greatness in these moments. Until then, lets just prepare ourselves and take care of each other. 



Sources - as mentioned



Sources :

Convalescent Plasma Therapy for Corona Virus Disease 2019: a Long Way to Go but Worth Trying

A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19

A New Study Indicates Asymptomatic People are Still Highly Contagious 

The convalescent sera option for containing COVID-19

WHO

coronavirus.jhu.edu

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