By Alexander Bernstein
First reported in Saudi Arabia in 2012, Middle East Respiratory Syndrome (MERS) is a coronavirus-caused respiratory illness that has claimed over a 100 lives in Saudia Arabia and has a deadly fatality rate of around 40%. Caused by a virus called MERS-CoV, this illness has since spread to 6 countries near the Arabian peninsula. With patients suffering from fairly generic symptoms such as cough, fever, and shortness of breath, MERS is often compared to the SARS epidemic, which infected over 8,000 people in Asia in 2013. Some of the most notable differences, however, include transmissibility and fatality rate. While MERS is more deadly (40% versus 10% fatality rate), it does not appear to have the same infectious capacity. As such, the disease has primarily been confined to the Middle East.
Such is no longer the case. Several weeks ago, as per a report from the Associated Press in New York, the first case of MERS in the United States was confirmed. As might be expected, the afflicted individual had recently returned from a trip to Saudi Arabia, where he had been in Riyadh as a healthcare worker. Flying from Riyadh to London to Chicago and then boarding a bus for Indiana, the man ended up in an Indiana hospital emergency room on April 27th.
Although the man is in a stable condition at the Indiana hospital as per a report from Dr. Anne Schuchat, the director of respiratory diseases at the CDC, there are many concerns regarding possible transmission of the disease during the man’s travels. With a typical five-day incubation period for MERS and the patient’s checking in at the hospital on April 27th, experts are still uncertain if he may have infected other individuals. Reporting as a spokesman for the CDC, Tom Skinner explains that although plane tickets can be tracked to determine who the infected man sat next to on his two flights, the “bus ride may be a challenge” since tickets aren’t recorded and monitored in the same way.
This particular likely-bat-originated coronavirus hasn’t been found to rapidly spread from person to person. However, localized outbreaks have occurred in hospitals and families where multiple healthcare workers have worked in close proximity to an infected patient.
While symptoms can be treated, no cure exists, and potential antibody virus-blocking treatments are still in the early stages of development. The identification of antibodies that attack the particular coronavirus does mark legitimate progress. As per a Harvard led group study, two separate antibodies have been found to interact with the surface of the MERS-CoV and prevent the spike shaped viral protein from attaching to human cells. Of further interest is the discovery that mutations allowing the virus to partially escape the antibodies also appear to result in impaired ability to replicate. Yet, despite the identification of these two antibodies, labeled as MERS-4 and MERS-27, which appear to demonstrate a synergistic effect, researchers are still far from a potential treatment. As Dr. Wayne Marasco, a leading researcher in the Harvard study explains, so far, progress on the matter is only nearing animal testing, with the lack of ideal animal models providing further hindrance to drug development.
By Ian MacArthur
In the effort to find a definitive cure for Human Immunodeficiency Virus (HIV), researchers will first have to discover a method of arresting viral replication in host cells. The cells of two young children with a congenital defect may provide a new means of preventing the replication of HIV in otherwise healthy people.
Two siblings, a boy of 11 and a girl of 6, have a genetic defect termed a congenital disorder of glycosylation (CDG), and their cells were found unsuitable for the replication of HIV and other viruses. The condition of the pair is unique, as the inability to facilitate viral replication is evident alongside hypogammaglobulinemia, which is a condition characterized by low levels of antibody: a mark of compromised immunity.
The diagnosis of hypogammaglobulinemia indicates that it is not a unique feature of the children’s immune systems that explains the inhibition of viral replication. Rather, this finding points to the CDG of the children as the cause. Glycosylation is the process by which carbohydrates are post-translationally added to proteins in the endoplasmic reticulum of cells. Glycosylated proteins are a particularly important class of compounds, as many of them are present at the cell surface and function as receptors involved in intercellular communication. The patients’ particular CDG, CDG-IIb, is caused by a defective gene that codes for MOGS, a protein found in the endoplasmic reticulum involved in the glycosylation of cell surface proteins.
The research team studying the patients’ cells discovered that only viruses with glycosylated proteins on the surface of their capsids were unable to replicate in the cells, indicating that improper glycosylation leads to an inability of viruses to infect other cells. Since viruses exploit the enzymes of host cells to replicate themselves, a defect in MOGS of a host cell will result in defective glycosylation of viral proteins.
A major implication of this finding is that it points to the use of MOGS inhibitors for halting the replication of virus in patients with HIV and other glycosylated viral diseases. More research will have to be conducted once potential MOGS inhibitors are identified.
The study is also interesting in that it sheds light on the methods of medical science. Unfortunately, CDGs can cause life-threatening neurological impairments due to the importance of glycosylated proteins in human development. Although the condition of the two children has provided insight into how HIV might be combated, the discovery comes at the price of their health. Often, the function of a protein or enzyme is identified by its absence in patients with genetic disorders. Thus, the progress of medical science is inextricably linked to morbidity and mortality. While this thought is certainly unsettling, it can also be viewed as an element of solace for patients suffering from rare disorders and their families. In this way, the antithesis of health can contain the way towards its recovery.