New Drug Stops Replication of Virus that Causes the Common Cold

New Drug Stops Replication of Virus that Causes the Common Cold

The common cold is usually a relatively minor inconvenience, although for some patients such as those with COPD, cystic fibrosis, or asthma, a cold can potentially be a life-threatening illness. While there are various treatments that can alleviate symptoms, there is no cure for the common cold.

Developing a cure for the common cold is problematic. There are more than 100 known variants of rhinoviruses that can cause the common cold, so a vaccine is not an option. Further, the viruses can mutate rapidly and develop resistance to any drug that targets them directly. However, a cure could well be just around the corner.

A team of scientists at University College London has developed a new class of drug molecules that are capable of preventing the common cold virus from replicating. Further, the molecules have also been shown to be effective at preventing the replication of other types of picornaviruses, including poliovirus and those responsible for causing foot and mouth disease.

The rhinovirus capsid relies on the human enzyme N-myristoyltransferase (NMT), which modifies the virus capsid protein VP0 through a process called myristoylation. Previous studies have shown that NMT is a prerequisite for capsid replication and infectivity. The researchers explain that “host NMT may therefore be an attractive antiviral drug target that is minimally susceptible to both serotypic variation and the propensity of the virus to mutate, because host NMT is an invariant factor in viral replication.”

While the researchers have previously developed NMT inhibitors, to date they have only managed to reduce activity of the human enzymes by a modest degree. However, the researchers have now developed a new class of human NMT inhibitor, called IMP-1088, which has been shown to be highly effective at reducing human enzyme activity and preventing virus replication.

“Remarkably, IMP-1088 significantly inhibited the production of infectious virus even when added up to 3 hours post infection, which suggests that efficacy can be maintained even in the face of an active infection.”

The compound has been shown to be effective in vitro. Now the researchers are hoping to move to preclinical in vivo testing, followed by clinical trials. First, they must conduct extensive toxicological studies and determine whether the benefits of the drug outweigh the risks.

Should that be the case, the researchers expect they will need to administer the drug in a way that will get it into the lungs rapidly, such as via a nasal spray.

If the drug is administered early enough it could prevent viral replication and thus serve as a cure for the common cold. Unfortunately, quick administration could be an issue. Symptoms of the common cold could be caused by other diseases and conditions: Hay fever for instance. Treatment would require a correct diagnosis, and also that diagnosis would need to be made extremely quickly – within a few hours.

“The way the drug works means that we would need to be sure it was being used against the cold virus, and not similar conditions with different causes, to minimize the chance of toxic side effects,” wrote the researchers.

Should the diagnosis prove incorrect, it is possible that resistance to the drug may not develop since the drug targets host myristoylation. “Viral mutations would not influence the inhibitor potency against a host enzyme,” wrote the authors.

The research is detailed in the paper – Fragment-Derived Inhibitors of Human N-Myristoyltransferase Block Capsid Assembly and Replication of the Common Cold Virus – recently published in the journal Nature Chemistry.

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