THROWING A WRENCH INTO CORONAVIRUS’S WORKINGS
Chinese physicians confront disease with cutting-edge science, traditional medicine
Almost everything about COVID-19 is debatable except for the fact that the disease first appeared in China and spread from there around the world. Chinese physicians were therefore the first to confront the disease and did so with a mix of cutting-edge science and traditional Chinese medicine. Researchers were quick to crack the genetic code of the SARS-COV-2 virus and map its molecular structure. To their credit, the Chinese scientists immediately released the information online, allowing others around the world to begin exploring possible routes to vaccines and treatments. Knowing the details of the structure of the virus and the tools it uses to infect cells is the key to finding ways to prevent the virus from replicating in the body.
A group of scientists from various research institutions in China just published an impressive collaborative effort in the prestigious journal Science that offers hope for a drug to prevent viral replication. The study focused on a specific enzyme, a protease, that the virus needs for its life cycle. Proteases are proteins that act as biological catalysts in reactions that chop other proteins into smaller fragments. The genetic material of the coronavirus, its single-stranded RNA, encodes for the production of “polyproteins” that are then broken down into simpler proteins by Mpro, the main protease. Those simpler proteins include the “spike protein” the virus uses to invade cells. The researchers hypothesized that if a means were found to inactivate the Mpro enzyme, then the ability of the virus to infect cells and replicate would be curbed.
Like all proteins, a protease is a long molecule composed of a chain of amino acids twisted into a specific three-dimensional shape. One of the turns of the twisted chain forms a pocket into which the proteins that are going to be chopped up fit. If this pocket were to be permanently occupied by another molecule, the Mpro enzyme would be unable to carry out its task. The Chinese researchers managed to identify the sequence of amino acids that form the pocket and then considered the features that a molecule would have to have to bind to those amino acids. They synthesized two prototype compounds believed to have the right shape and binding ability and tested them on the enzyme isolated from the virus. Indeed, both compounds blocked the activity of the enzyme. Of course, this was just a “test tube” trial and only amounts to a proof of concept, but it is encouraging. Even more so, because tests in mice and dogs showed that the compounds caused no adverse effects and had a long enough half-life to potentially serve as a treatment.
What is truly amazing here is that the internal workings of a virus and all the molecular machinery involved in replication can be determined in such detail and that molecules with a specific structure cannot only be conceptualized, but can actually be synthesized to throw a wrench into the works. This is the brilliance of modern science.
Interestingly, at the same time that they are pushing the envelope of cutting-edge science, Chinese researchers are also exploring the use of traditional Chinese medicine in combating COVID -19. There are a large number of clinical trials underway with a plethora of herbal preparations that are unfamiliar to western scientists. We really do not know what to make of capsules of Huo Xiang Zheng Qi Shui, or injections of Xi Yan Ping. It is certainly possible that something will emerge from these trials since traditional Chinese medicine has shown efficacy in some conditions. For example, Artemisia annua, has been used for more than 2,000 years to treat fever, and with the help of modern science has given rise to an extract that contains the active ingredient artemisinin in a standardized dose for the treatment of malaria.
On the other hand, deer penis, tiger eyes, rhino horn, donkey hide, ground goat horn, dried placenta or bear bile have no evidence of efficacy for anything, yet they are popular among segments of the Chinese population. Aside from being ineffective, there is a dark side to the procurement of some of these “remedies.” Bears are raised in captivity, sometimes for decades, for the sole purpose of inserting a catheter into their gall bladder to drain the bile, causing pain and often infections. Bear farms are legal in China, but on top of the myth that the bile has various benefits is the myth that bile from wild animals is more effective than from farm-raised ones. This leads to the poaching of wild animals putting pressure on their population.
Bears are not the only target of poachers. Rhinoceros horn traditionally is believed to have aphrodisiac properties, but is now also being touted as a treatment for COVID-19 infection. Angong Niuhuang Wan is a traditional Chinese medicine that consists of 11 herbal and mineral components including potentially toxic mercury and arsenic sulphides that is “approved” for the treatment of fever and stroke. According to a Chinese government website, it also incongruously contains ground buffalo horn. However, some “underground” products contain rhino horn instead because it is thought to be more effective. COVID-19 not only affects our lives but unfortunately that of bears, rhinos and tigers as well. Joe Schwarcz is director of Mcgill University’s Office for Science & Society (mcgill.ca/oss). He hosts The Dr. Joe Show on CJAD Radio 800 AM every Sunday from 3 to 4 p.m.