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Biological Chemistry

Cell-Based Screens Detect Drugs Active Against Middle East Respiratory Syndrome

Preliminary results will be tested in animals infected with the MERS coronavirus

by Carmen Drahl
June 2, 2014 | APPEARED IN VOLUME 92, ISSUE 22

The coronavirus that causes Middle East respiratory syndrome (MERS) first appeared in humans in 2012. An unexplained spike in MERS cases this spring, including the first two cases in the U.S., has placed public health officials on alert. About 30% of the more than 600 confirmed infections have proved fatal. No specific treatment exists for MERS, so researchers are seeking drugs or vaccines to combat the disease in humans or its animal hosts. Two screening efforts, each of a different small library of FDA-approved drugs, have turned up potential MERS leads (Antimicrob. Agents Chemother. 2014, DOI: 10.1128/aac.03036-14 and 10.1128/aac.03011-14). One screen was carried out by Matthew B. Frieman of the University of Maryland School of Medicine and colleagues. The other screen was conducted by Eric J. Snijder of Leiden University Medical Center, in the Netherlands; Johan Neyts of Catholic University of Leuven, in Belgium; and coworkers. After confirmatory tests, the two hits the teams had in common were chloroquine and chlorpromazine. Both compounds prevent endocytosis, which is the cell’s process of engulfing outside molecules and absorbing them. This finding suggests the compounds interfere with entry of MERS into cells. The teams are preparing to verify their results in small-animal studies.

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Comments
Jim Parsons (October 25, 2015 4:43 PM)
I’ve heard of the MERS virus before --- the drugs that I heard of first that inhibit was in the June 2, ’14, page 24 of C&EN. Namely chloroqine (an antimalarial) and chlorpromazine (an antipsychotic drug). The article, Early Hits for MERS Inhibitors’ described that the drugs inhibit endocytosis, which I thought was pretty interesting. And clever too. Liked the described mechanism. I don’t know about the last drug but the first one that can be used for malaria might be expensive. Which would limit its use, which would not help as many folks as one might hope. There is another material, butylhydroxytoluene or \BHT, that has been known since the late 6os to disrupt the viral coat of some viruses thereby reducing the infectiveness of a virus particle. The key to this is the ratio of lips or fatty materials to proteins in the viral coat or shell. With those viral types having more lipids in their viral coats being more susceptible to disruption (for lack of a better word) than those that have viral coats that are more protein based. An example of a susceptible virus is the one that causes Herpes and one that is not susceptible is Polio. The starting dose is something like 50 mg or so and is taken neat and orally --- a glass of water? The number of times that the dose is given depends on the virus --- they come in crops and that is when you want to take the dose. Some of the viruses that cause intestinal problems and are susceptible ‘crop’ every 2 to 4 hours depending on the virus --- the ‘cropping’ can be guessed at when the person has to head of to the toilet. It is my understanding that BHT is effective for about 2/3 of all human infective viruses. Food quality BHT can often be gotten through your local butcher or meat packer as BHT has been used (I think) since the early 50s as a food preservative for potted foods such as hot dogs and salami (again, I think). Hope this helps.
Jim Parsons (November 16, 2015 3:23 PM)
I see that the information is still on the web page. Suggesting that some may have found it worthwhile. I am pleased. Although, I might have paid a little more attention to spelling and the like! An effective and inexpensive way to stop a diarrhea, especially for the young and us older folk, some in nursing homes, can’t be overstated I think. A particularly nasty intestinal virus went through and killed a half dozen or so (population was about 35 individuals) in less than a week in the nursing home that my Mom was staying in recovering from her hip replacement surgery (I was able to get her and the other gal in that room some BHT -- Mom shared.). Butylhydroxytoluene (also knows as BHT) might be a good first-line defense against intestinal virus --- well other viruses too? As noted previously, the material's affects been known since the sixties. It is a wonder why it is not often used, perhaps because of its use as a food additive limits its use in clinical settings? A legal matter then? A puzzle it is.

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