How to stop SARS viruses from reproducing

3:47 PM
The bright spot surrounded by a corona looks harmless, but it is a deadly pathogen: A corona virus causing SARS. The virus was first identified by the Bernhard Nocht Institute for Tropical Medicine in Hamburg. Picture by Bernhard Nocht Institute for Tropical Medicine.

In times of the “bird flu” SARS seems to be no threat anymore. This notion is deceptive. Experts assume that viruses causing the severe acute respiratory syndrome SARS, or other related corona viruses, could re-emerge at any time and might pose a global public-health threat.

From November 2002 to June 2003, 8,500 patients were infected with an at that time unknown pathogen originating in southern China; 800 humans died. Then, the epidemic was controlled and it’s cause detected. The pathogen was a novel corona virus. Such viruses are extremely alterable.

Now, researchers of the “Leibniz-Institut für Molekulare Pharmakologie” (FMP) in Berlin have synthesized substances that target a vital enzyme of the SARS virus, namely it’s main protease. “We were systematically looking for molecules to prevent the corona virus from reproducing itself”, says Prof. Jörg Rademann. He heads the group “Medical Chemistry” at the FMP. Rademann adds: “We hope that our research can help to produce suitable drugs against such viruses in a short time, especially in the case of a new epidemic.”

The main protease proved to be a good starting-point for the researchers: The group of Prof. Rolf Hilgenfeld at the University of Lübeck provided the protein and solved its structure. The viral enzyme cuts long protein molecules manufactured by the virus in the host cell into small pieces. The main protease is essential for the reproduction of all corona viruses and it has an almost identical structure in all of these pathogens. Thus, once a substance that attacks the main protease is found, scientists would have a wide range of possibilities to fight different corona viruses.

Rademann and his team, together with colleagues, have synthesized for the first time molecules that attach themselves to the main protease without being chemically reactive. Most importantly, this process is reversible, thus minimizing side-effects of potential drugs. The researchers presented a collection of substances that resemble the natural substrate of the main protease.

Even if it is still a long way from such a collection to suitable drugs, the newly synthesized peptide aldehydes mark an important step towards a therapy for SARS. The next goal is to identify the most effective peptide aldehydes out of the collection and then to further optimize the substance. “If we are successful, the next outbreak of SARS will pose a much smaller threat to public-health and we will not be helpless”, says Rademann.

Mutated Bird Flu Virus Might Not Spread Easily

3:41 PM
Although many scientists have been concerned that the H5N1 bird flu virus may mutate one day and become easily human transmissible, a recent study seems to indicate that it might not spread easily among humans. Researchers from the Centers for Disease Control and Prevention (CDC), USA, tried to combine a common human flu virus with H5N1 and found it does not spread easily.

This could mean that the mutated virus may not be such a giant threat to global human health. You can read about this study in the Proceedings of the National Academy of Sciences, August 2.
Scientists infected ferrets with genetically engineered H5N1 viruses and found that the infected animals did not spread their illness to other healthy ferrets - all the animals were very close to each other. They also found that the ‘mutated’ virus was not as virulent as the original H5N1.

(Virulent = Potent, powerful)

The H5N1 bird flu virus strain may one day mutate by exchanging genetic information with a normal human flu virus. It could infect a human who also had the normal human flu and mutate. Dr. Jackie Katz, one of the researchers, said the study was carried out to see what would happen when H5N1 acquired the genetic changes needed for better transmission.

The researchers mixed H5N1 genetic material with other viruses. Ferrets and humans catch and transmit flu in a very similar way, hence, ferrets were used in this study. Ferrets infected with ‘mutated’ H5N1 viruses did not pass on the virus to healthy ferrets in the same cage.

This does not mean that a mutated H5N1 will never be dangerous to humans. It just means that the chances of a mutated virus being a serious threat to global public health are smaller than feared. There are 50 possible combinations of the viruses.

The current H5N1 virus can only infect a human deep down in the lungs, not the upper respiratory tract. This has advantages and disadvantages:


– It is more difficult to make someone ill because the virus has to go a long way down. A human has to be exposed to a large cluster of the virus for longer to get ill.
– An infected human who coughs and sneezes will not emit many viruses, because they are deep down in the lungs - that is one of the reasons humans cannot infect other humans easily.


– A human who has an infection deep down in the lung(s) will not know about it until it has progressed further than a person who has an upper-respiratory infection. This is one of the reasons the human death rate is so high.

For the H5N1 to become more human transmissible will most likely need to mutate so that it infects the upper-respiratory tract. If it manages to do this, the theory goes, it will spread more easily, but will probably not be so deadly.

Test Tamiflu, A Tamiflu Review

3:31 PM

Bird Flu Studies Urgently Needed to Test Tamiflu, WHO Says
More studies are urgently’ needed to determine how bird flu patients can be best treated with oseltamivir, the antiviral drug marketed by Roche Holding AG as Tamiflu, the World Health Organization said.

Tamiflu is approved to treat seasonal flu. No direct clinical trial evidence shows the medicine is effective in treating people infected with the lethal H5N1 avian influenza virus because no such studies have been conducted, the Geneva- based United Nations health agency said yesterday.

“Because the optimal dosage has not been resolved by clinical trials, and because H5N1 infections continue to have a high mortality rate, prospective studies are needed urgently to determine optimal dosing and duration of treatment,'’ the WHO said in a statement on its Web site.
The WHO and governments around the world are stockpiling Tamiflu for use as a prophylactic against any potential influenza pandemic. The medicine is also one of several drugs being used to treat patients with H5N1, which health officials worry may mutate into a form that’s more contagious to humans.

Since 2003, H5N1 has killed at least 98 of 177 people infected, the WHO said on March 13.
There is limited evidence suggesting that some oseltamivir can reduce the duration of viral replication and improve prospects of survival, provided it is given within 48 hours following symptom onset, according to the WHO’s fact sheet on avian flu, published on the Internet. Prior to an H5N1 outbreak in Turkey earlier this year, most patients were detected and treated late in the course of illness, it said.

Turkish Data
Roche said last week it has data from 21 patients in Turkey who took the drug after being infected with H5N1. Four of the patients were given the drug “very, very late'’ and died, David Reddy, head of Roche’s pandemic task force, said. The remaining patients recovered and were discharged from the hospital.

“The evidence for effectiveness of oseltamivir in human H5N1 disease is based on virological data from in vitro, animal models, and limited human studies and extrapolation from the results of trials in patients with ordinary human influenza, ‘’ the WHO said.
Optimal treatment of H5N1 cases using oseltamivir may be different than recommended for seasonal flu, the WHO said in the statement yesterday. For seasonal flu, it is recommended that adults take 75 milligrams of oseltamivir twice a day for five days.

In H5N1 cases, it is possible that severely ill patients might benefit from taking the medicine for seven to 10 days or given as much as 300 milligrams a day, the WHO said, adding that “prospective studies are required.'’

Higher Doses
Gastrointestinal side effects in particular may increase with higher doses, particularly above 300 milligrams a day, the WHO said. There is no adequate data on the use of oseltamivir in pregnant women, it said.

“Animal toxicology studies do not indicate direct or indirect harmful effects with respect to pregnancy or fetal development,'’ the WHO said. “Decisions to use oseltamivir in pregnant women should be made on a case by case basis where the potential benefit to the mother justifies the potential risk to the fetus.'’

Basel, Switzerland-based Roche said on March 16 it will use 15 partners, including Sanofi-Aventis SA and Clariant AG, to increase production of Tamiflu by 33 percent by year’s end.
Based on the current manufacturing capacity, it will take a decade to produce enough oseltamivir to treat a fifth of the world’s population, according to the WHO.

Bird Flu Vaccine Makes Big Strides

9:38 AM
A vaccine for avian influenza has been developed by the Bhopal-based High Security Animal Disease Laboratory. This discovery brings India on par with China, Pakistan, Indonesia and Thailand. The vaccine used killed H5N1 virus and can be used during a H5N1 bird flu outbreak.
The immune response is good and the vaccine offers protection of above 90 percent. The lab is now in the process of looking into the duration of protection.

Dr. H.K. Pradhan, Joint Director of the laboratory told the Hindu, “According to the literature, the immunity [protection] can last up to six months.” The question of increasing the duration with a booster dose is under investigation.

The vaccine has been tested for safety, dosage, and route of inoculation. Dr. Pradhan said, “We found the intra-muscular [route] to be better.”
On the whole, there is little chance of the avian flu occurring following vaccination since the vaccine uses a killed virus to bring on a good immune response.

The vaccine was developed over a short period of time since the lab had been working on bird flu for the last six years. The Indian Council of Agricultural Research had requested research on a vaccine following the first outbreak in India in February 2006 and it was completed in early July.
Dr. Pradhan revealed, “We had the viruses collected during this year’s outbreak and the cell lines taken five years ago.”

The vaccine may be used right after an outbreak to control the spread of the virus as well as for vaccination prior to an outbreak. However, vaccination before an outbreak is not advisable since the vaccine has its limitations.

In a process referred to as “ring vaccination” poultry in a 5 km (3 miles) radius of the location of outbreak has to be killed followed by vaccination on birds in a 5-10 km (3-6 miles) radius or more. The cost and the licensing of the technology for commercial use remains to be worked out.

New Bird Flu Vaccine

9:22 AM

A British company’s report that it may have come up with a viable bird-flu vaccine comes as a rare dose of good news this summer. GlaxoSmithKline says that the new vaccine appears to work very well in small amounts, improving the prospect that millions could be shielded from a possible pandemic.

Since it began spreading a few years ago, the avian-flu strain known as A(H5N1) has sparked fears among health officials that it could turn spectacularly destructive. Although it has mainly attacked birds, it has killed more than 130 people who presumably came in contact with infected fowl. So far, it does not appear to be spreading from person to person. But if it mutates, as many scientists fear, that could change. Meanwhile, the virus has steadily extended its range, from Asia to Europe and Africa.

So far, drug companies have had little luck coming up with a potent vaccine. Countries and individuals have been stockpiling the flu-fighter Tamiflu, which has shown some success in treating infected humans but is difficult to make.

Now, GlaxoSmithKline says it has created a vaccine that protects more than 80 percent of those who receive just two shots. An added substance (and trade secret) permits a relatively small dose of the main active ingredient to be used.

Public-health officials reacted to the news with cautious optimism. More testing must be done to see if the documented immune-system response holds up outside simple blood tests. Another concern is that the new vaccine could prove ineffective if the virus mutates.

Nevertheless, the preliminary evidence suggests that the vaccine should get a speedy review from the U.S. Food and Drug Administration. If approved, it could conceivably be made on a large scale, then saved for distribution in the event of a pandemic. GlaxoSmithKline estimates that it could produce 60 to 70 million doses a year.

Despite health officials’ considerable fears of an outbreak, it remains unclear how grave a problem bird flu will turn out to be. However, having a response at hand is far better than waiting for the worst to happen. Hurricane Katrina has at least taught us that.

Symptoms of Bird Flu

5:25 PM

Symptoms of bird flu in humans:

The current H5N1 strain is the same strain that killed an estimated 25-50 million people in the 1918 flu worldwide pandemic. Detecting bird flu early can be critical to a patient’s survival. Because bird flu symptoms are similar to ordinary human flu, it is important to separate the presenting symptoms.

Common bird flu symptoms:
High fever (101-104 degrees Fahrenheit)
Cough - when mucus is produced it may be bloody
Shortness of breath
Low white blood cell counts
Chest “crackles” heard with a stethoscope
Bleeding gums
Bleeding nose

Not common: These symptoms are common to influenza but not common to bird flu:
Sore throat
Runny nose

Like ordinary flu, bird flu presents with high fever (101-104 degrees Fahrenheit) and cough. There are two distinguishing features that may indicate bird flu: (1) shortness of breath (usually accompanied by a higher than normal respirations rate) and/or (2) diarrhea. The diahrrea can be bloody and may precede the cough and respiratory symptoms by up to one week. The cough may or may not produce sputum, but when it does it can be bloody.

Almost all patients present with what is called “crackles” in their chest, which is a sound that a health care practitioner can hear with a stethoscope. Bird flu kills primarily by attacking the tissues in the lungs, so it is really important to have your chest symptoms evaluated by a medical professional if bird flu is in your area. Another thing your doctor can check for is laboratory findings. One well documented study reports significantly low white blood counts as a specific indicator in bird flu cases.

With bird flu, it is not typical to have a sore throat, conjunctivitis, a rash or a runny nose. It is with normal flu.

The average time between exposure and onset of illness was 2-4 days when bird flu first appeared in 1997. Recent reports indicate the range could now be 5-8 days, with 2-4 days still the most common. The median time from death to onset of illness is 9 days. Recent bird flu cases have caused high rates of death in infants and children. The bird flu is fatal in over 50% of adult cases worldwide. The death rate was actaully 89% for children in Thailand at one point. Bird flu is particularly dangerous for young people, and close attention should be paid to infants/children/teenagers with the above referenced symptoms.