Antiviral Drugs

An article in The Star of Malaysia illustrates why the public is often confused by stories about viruses in the popular press.

The article reports that ‘a four-man medical research team from the University Malaya Medical Centre has achieved a first by discovering an anti-virus for dengue fever from herbs’.

Let’s take apart this sentence to understand what it means.

Dengue fever is a disease caused by Dengue virus. It is transmitted by mosquitoes and is endemic (restricted to a locality or region) in the Caribbean, Central and South America, Africa, and Southeast Asia. It is an extremely important disease as billions of people in these areas are at risk. The first infection with Dengue virus is not often very serious (fever, severe headache, back and limb pain, rash). The problem arises when a person is infected a second time, when a fatal disease, called dengue shock syndrome, may occur. As a result of the serious nature of dengue shock syndrome, much effort is being devoted to producing vaccines and antiviral drugs to prevent the disease.

As is so typical for science reporting in many newspapers, this article provides little information on what exactly has been done. We are only told that the team has discovered an ‘anti-virus…from herbs’. I speculate that they have found that an extract from a plant can block virus infection. The article further suggests that capsules containing this anti-Dengue virus drug will be available early next year.

What exactly have the investigators in Malaysia done? There are two general ways of discovering antiviral drugs. The oldest approach, called ‘blind screening’, involves searching through random chemicals and natural product mixtures (e.g. plant extracts) for compounds that block virus replication in cell cultures. When a ‘hit’ is obtained – in other words, a compound that blocks virus replication in cells – it is further tested for safety and efficacy in animals. The specific inhibitory molecule is identified and perhaps further modified to reduce toxicity and improve efficacy. After testing hundreds or thousands of compounds, the antiviral may then be evaluated in humans (clinical trials). One notable antiviral discovered in this way in the 1960s was amantadine (also known by the trade name Symmetrel), used to treat influenza infections. The second approach to identifying antiviral drugs iscalled ‘mechanism-based screening’; we’ll talk about that in a subsequent post.

Although plants are known to have medicinal effects, and indeed contain antimicrobial compounds, none have been reported in the scientific literature as having been tested against Dengue virus. I conclude that the Malaysian group has found that a crude extract of an herb inhibits Dengue virus replication in cells. To think that such extracts could be used directly in people is ludicrous. Plant extracts contain many different compounds and can even be toxic. It would be foolish to give such extracts to humans without purifying the anti-Dengue virus molecule – the side effects could be fatal.

Further increasing my skepticism of this report is the claim that this discovery is ‘a first’. A search of the scientific literature (PubMed) reveals that other antivirals against Dengue virus have already been described, although none have been used in humans.

There are at least two morals to this story. One, don’t always believe what you read in the paper. Two, safe and effective antiviral compounds are very difficult and costly to identify. Unfortunately, a Dengue antiviral is still many years away.