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Various treatments to fight COVID-19

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Oleh
Various countries have conducted research to find effective treatments against the type of SARS-CoV-2 virus that causes COVID-19 infection.


SARS-CoV-2 structure.
Characteristics of SARS-CoV-2 RNA :
  • Single stranded beta RNA virus Coronavirus.
  • Enveloped, positive-sense.
Produces protein :
  • Non-structural proteins : 3-chymotrypsin-like proteases, papain-like proteases, helicases, RNA-dependent RNA polymerases.
  • Structural protein : glycoprotein.
  • Accessory protein.
Potential treatment for SARS-CoV-2 virus.
Neutralizing antibodies.
The mechanism of attachment of SARS-CoV-2 through bonding between protein S and receptors on the cell surface ➡ neutralizing antibodies that target S protein on the surface is considered to be a therapeutic choice ➡ after the SARS-CoV-2 genome sequence is obtained ➡ a strategy using large animals (goats) , sheep, cattle) to make neutralizing antibodies ➡ after that polyclonal antibodies from these animals are purified ➡ for short-term neutralizing antibodies Oligonucleotide Antivirus Transfer, passive antibodies from the patient's serum that has been declared cured, inhibitors of ACE2 receptor bonds, ACE2 Immunoadhesin strategies can be performed ➡ see outbreaks that develop rapidly and have different immune responses between species, so this strategy is difficult.

Oligonucleotide.
Targeting small interfering RAN (siRNA) or antisense oligonucleotides (ASO) to fight viruses. The difficulties of this method, namely :
  • It's hard to get an RNA sequence domain because it's not yet known.
  • How to send oligonucleotides to the lungs.
  • Lipid nanoparticles have been found to mediate and send oligonucleotides to the lungs, but their effectiveness is unclear.
Antivirus.
Potential targets are :
  1. Viral polymerase.
  2. Protease inhibitors.
Both are components of antiviral HIV and HCV. In some reports, Lopinavir and Ritonavir have efficacy against SARS. Further research is needed to find out more about the effectiveness of this drug against the SARS-CoV-2 virus. Currently clinical trials to determine the effectiveness of Lopinavir + Ritonavir and Arbidol are being conducted in China. But no results have been reported to date.

In another study, Remdesivir + Chloroquine was used in vitro to fight SARS-CoV-2.
  • Remdesivir : an adenosine analogue that causes premature termination of the virus.
  • Chloroquine : antimalarial and autoimmune drugs that are widely used and have potential as broad spectrum antiviral drugs. Chloroquine works by increasing endosomal pH and interfering with SARS-CoV cellular receptor glycosylation.
Passive transfer of antibodies from the serum of patients who have been declared cured.
  • Patients who are infected and have recovered from COVID-19 will make antibodies with high titers.
  • Patients who have recovered can donate their plasma and then inject it into patients who are still sick.
This technique has been used in Ebola outbreak patients in 2014-2015. The problem that arises is because of the high outbreaks, the availability is also decreasing and there is variability in antiviral potential.

Inhibiting the binding of ACE2 receptors.
This strategy gives the ACE2 binding agent to the patient, so that the virus has no attachment and cannot replicate.

Use the small receptor-binding domain (RBD) of the S SARS protein which was known as the key domain of ACE2 receptor binding when the virus first entered ➡ this condition has been proven in cell culture, maybe this can be used for SAR-CoV-2.

Inserting antibodies that will bind to ACE2 protein penelitian in the study found effective results in preventing the entry and replication of the SARS virus.

Problems that arise are :
  • It is possible that the body formed antibodies to the SARS protein.
  • Substitution of ACE2 receptors on the cell surface will affect how often this therapeutic protein is needed.
  • Steps that can be taken are to increase the concentration of anti-ACE2 therapy to the lungs through nebulisation.
ACE Immunoadhesin Strategy.
  • Binding the corona virus directly, rather than protecting cells from viruses.
  • Research using soluble ACE2 receptors can inhibit the SARS virus from infecting cell culture.
  • Soluble ACE2 needs to be converted to the immunadhesin format and combined with the Fc immunoglobulin domain (ACE2-Fc) to increase the life time of the molecule and increase the function of the immune system effector to fight the virus.
As research develops to find effective treatments against SARS-CoV-2, it is hoped that this disease can be controlled immediately. The studies carried out to date have shown promising results.
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