In the last 20 years, the world has seen three different coronavirus outbreaks – SARS-CoV-1 (causing SARS) outbreak in 2004, MERS-CoV (causing MERS) outbreak in 2012 and now the SARS-CoV-2 (COVID-19) pandemic. The three viruses cause respiratory illness, however, SARS-CoV-2 is more transmissible and less lethal than SARS-CoV-1 and MERS-CoV. The former has infected millions worldwide in the past ten months while SARS and MERS outbreaks affected over 8,000 and 2,000 people respectively.
Since the three viruses belong to the same family, experts believe that they may share some vulnerabilities which can be exploited to treat the diseases caused by these viruses. About 200 researchers from 14 different institutions across six countries joined hands to find these vulnerabilities.
The findings of the research, now published in the journal Science, suggest that these vulnerabilities may also be used to deal with and quickly find a treatment should a new coronavirus outbreak occur in the future.
Similarities in host-virus interactions
As per a news release by the European Molecular Biology Laboratory – European Bioinformatics Institute (one of the institutions included in the study), the researchers built on previous studies concerning host-protein interactions of SARS-CoV-2 to find the where viral proteins are located and how they interact with the host cell infected by different coronaviruses.
The researchers made three different human-protein and viral protein interaction maps to identify the molecular mechanisms in these viruses. They found that several proteins in all these viruses are conserved (do not mutate) and hence may have a crucial role in infection. These proteins usually take up the certain specific cellular compartment, wherever they are functioning or wherever their corresponding host protein is present. However, the same cellular processes (viral host interactions that are the same in two or more coronaviruses) may be targeted by different viral or host proteins in different coronaviruses. Since we now know more about these proteins, we can target them with the right drug.
The researchers also found that the three viruses share at least five different host-protein interactions that can be targeted by the same therapy.
Genetic screening identified more host factors that can affect all three viruses and specific host factors that can affect SARS and COVID-19 proliferation and hence can be used to target therapy.
The studies showed that increased sIL17RA (a protein) in plasma corresponds to a lower risk of COVID-19. This is because the protein binds to SARS-CoV-2 and disrupts its genetic structure.
The authors mentioned in the study that this pathway should be studied more for its use as both diagnostic and therapeutic target for COVID-19.
Druggable targets that interact with various coronaviruses
To study the druggable host factors against the common targets in the three coronaviruses identified in the study, the researchers analysed clinical data from over 738,000 COVID-19 patients in the US.
It was found that patients who received antipsychotic drugs targeting the sigma-ligand fared better than those who got other antipsychotics. Sigma receptors are specific receptors present in various tissues, especially the brain and play a role in intracellular signaling and regulation of metabolism. These receptors have previously been suggested to be a potential target for COVID-19 treatment since SARS-CoV-2 interacts with these receptors to infect the host.
However, more studies are still needed to better understand the effect of these drugs and how exactly they mediate their function.
For more information, read our article on Coronavirus infection.
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