Novel approach to combating MERS-CoV The
Novel approach to combating MERS-CoV
The outbreak of Middle East respiratory syndrome (MERS) in 2012 has made it a health problem that can not be ignored. Now scientists have developed a new approach to tackle this problem.
MERS is a viral respiratory illness that was first identified in Saudi Arabia in 2012. Until now, the infectious disease has been reported in 27 countries, according to the WHO. But the majority cases of MERS occurred in Saudi Arabia. Currently, there is no vaccine or specific treatment for MERS-CoV infection. In some regions, the mortality rate from the virus is as high as 41%. To tackle this urgent health threat, many research institutes and pharmaceutical companies are working to develop MERS-CoV vaccines and therapies.
One such group, consisting of scientists at the University of Toronto, the University of Manitoba, and Leiden University Medical Center, focused on the ubiquitin system in human cells that the virus uses to infect and spread in the body. The ubiquitin system, which contains hundreds of proteins, functions in various cellular processes, such as antigen processing, apoptosis, immune response and inflammation, and viral infection. However, many viruses including MERS-CoV produce deubiquitinating (DUB) enzymes that alter the ubiquitin system in a way that suppresses host antiviral innate immune responses. This enables the viruses to multiply and destroy the host tissue.
Using phage-displayed ubiquitin variant (UbV) libraries, the researchers identified inhibitors that effectively and selectively target the DUB enzymes of MERS-CoV. Then they tested the ability of UbVs to inhibit MERS-CoV in cell culture and found that expression of UbVs during MERS-CoV infection resulted in significantly lower virus titers, demonstrating the remarkable potency of UbVs as antiviral agents.
Collectively, the study establishes an approach to produce inhibitors that combat MERS-CoV by using UbVs. Since the approach may also apply to other viruses, findings of the study are of great importance. Moreover, the new approach takes only several weeks to produce viral inhibitors. This is a huge advantage over small-molecule approaches which often takes years. With this rational protein design technology, scientists may be able to quickly develop treatments for a broad spectrum of viral pathogens that infect humans, livestock and plants. During the outbreak of infectious disease, the shorter the time to produce potent therapies, the more lives we can save.
Like MERS-CoV, the Crimean-Congo hemorrhagic fever virus (CCHFV) also encodes DUB enzymes essential for virus replication. The researchers used the same approach to generate protein-based inhibitors targeting CCHFV’s DUB enzymes.
Previous studies have identified the virus DUB enzymes as promising antiviral drug targets. But virus DUBs and human DUBs share some structural similarities, making it different to selective small-molecular virus DUB inhibitors. The new study represents an alternative strategy to target virus DUBs.
The study “Potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants” is published May 18, 2017 in PLoS Pathogens. (Cusabio aims to provide excellent quality reagents for research, such as Recombinant EDNRB and ubiquitin.)
The outbreak of Middle East respiratory syndrome (MERS) in 2012 has made it a health problem that can not be ignored. Now scientists have developed a new approach to tackle this problem.
MERS is a viral respiratory illness that was first identified in Saudi Arabia in 2012. Until now, the infectious disease has been reported in 27 countries, according to the WHO. But the majority cases of MERS occurred in Saudi Arabia. Currently, there is no vaccine or specific treatment for MERS-CoV infection. In some regions, the mortality rate from the virus is as high as 41%. To tackle this urgent health threat, many research institutes and pharmaceutical companies are working to develop MERS-CoV vaccines and therapies.
One such group, consisting of scientists at the University of Toronto, the University of Manitoba, and Leiden University Medical Center, focused on the ubiquitin system in human cells that the virus uses to infect and spread in the body. The ubiquitin system, which contains hundreds of proteins, functions in various cellular processes, such as antigen processing, apoptosis, immune response and inflammation, and viral infection. However, many viruses including MERS-CoV produce deubiquitinating (DUB) enzymes that alter the ubiquitin system in a way that suppresses host antiviral innate immune responses. This enables the viruses to multiply and destroy the host tissue.
Using phage-displayed ubiquitin variant (UbV) libraries, the researchers identified inhibitors that effectively and selectively target the DUB enzymes of MERS-CoV. Then they tested the ability of UbVs to inhibit MERS-CoV in cell culture and found that expression of UbVs during MERS-CoV infection resulted in significantly lower virus titers, demonstrating the remarkable potency of UbVs as antiviral agents.
Collectively, the study establishes an approach to produce inhibitors that combat MERS-CoV by using UbVs. Since the approach may also apply to other viruses, findings of the study are of great importance. Moreover, the new approach takes only several weeks to produce viral inhibitors. This is a huge advantage over small-molecule approaches which often takes years. With this rational protein design technology, scientists may be able to quickly develop treatments for a broad spectrum of viral pathogens that infect humans, livestock and plants. During the outbreak of infectious disease, the shorter the time to produce potent therapies, the more lives we can save.
Like MERS-CoV, the Crimean-Congo hemorrhagic fever virus (CCHFV) also encodes DUB enzymes essential for virus replication. The researchers used the same approach to generate protein-based inhibitors targeting CCHFV’s DUB enzymes.
Previous studies have identified the virus DUB enzymes as promising antiviral drug targets. But virus DUBs and human DUBs share some structural similarities, making it different to selective small-molecular virus DUB inhibitors. The new study represents an alternative strategy to target virus DUBs.
The study “Potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants” is published May 18, 2017 in PLoS Pathogens. (Cusabio aims to provide excellent quality reagents for research, such as Recombinant EDNRB and ubiquitin.)
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