Functionality Of Antiviral Gene RSAD2 Discovered
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Functionality Of Antiviral Gene RSAD2 Discovered

Researchers at Albert Einstein College of Medicine have discovered, for the first time, how the antiviral gene called RSAD4 prevents a remarkable range of human viruses from multiplying through a unique compound known as ddhCTP. The compound offers a novel approach for attacking viruses which the researchers could replicate to develop a new potent drug that fights off various disease-causing viruses

Humans and other mammals normally have RSAD4. Steven C. Almo, leader of the study and a professor at the Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology at Einstein says that this is the safest platform they can use for creating a potent antiviral compound.

“The way this compound disrupts virus, most particularly the Zika virus, from replicating is unbelievably remarkable,” says Dr. Almo. It simply attacks its main replication machinery to prevent the Zika virus from spreading further. Scientists believed that this mechanism could be replicated to treat other viruses. However, they first need to test the compound’s reaction to other viruses to validate its efficacy.

Dr. Almo says that we’ve been living with ddhCTP for millions of years now. “And it has worked on its own to ward off viruses from our body,” says Dr. Almo. “If we can further modify the RSAD4 to the compound ddhCTP, we could actually create a more potent drug that doesn’t only disrupt the replication of Zika virus but other viruses as well.”

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Finding how RSAD4 Defeats Viruses

Every human cell that is infected with viruses releases proteins called interferons, which signals hundreds of gene expressions. One of these genes is called RSAD2 – a gene that codes for the enzyme “virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible” or viperin.

In their study, viperin inhibits different disease-causing viruses like hepatitis C, rabies, and HIV-1. Several studies have already been conducted to observe how viperin exerts anti-viral compounds but most scientists failed due to the gap in technology.

Today, scientists have revealed that viperin catalyzes the conversion of nucleotide called CTP (cytidine triphosphate) into a structurally similar compound, or analog known as ddhCTP. This compound is responsible for sabotaging the replication process.

A safer template for more potent drugs

Dr. Almo’s colleagues at Pennsylvania State University shows that ddhCTP also helps in preventing the replication of other viruses such as the Zika virus. “I believe that the ddhCTP may be able to inhibit the replication of all other flaviviruses including dengue, West Nile, yellow fever, Japanese encephalitis and hepatitis C.” Flaviviruses are a group of RNA viruses that usually have arthropod vectors and are responsible for a variety of serious diseases.

Dr. Almos says that ddhCTP reveals a completely “novel approach” to design a new antiviral drug. “We are hoping that we can generate variants of this molecule the natural way so we can provide a safer way to develop new drugs,” says Dr. Almo. “The problem with artificial nucleotide analogs is that they can be quite toxic although they yield the same results.”

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At present, the team is conducting further studies for the modification of the compound. The study is funded by different grants from the National Institute of Health, Pennsylvania State University Start-up Funds, and the Price Family Foundation.

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