Markets offering wildlife including pangolins are thought to have served as the springboard for the emergence of SARS-CoV-2, the coronavirus that causes COVID-19 disease. Photo credit: Wikipedia.
By Kambiz Shekdar, Ph.D.
Perhaps no one could have imagined that a new cousin of the same virus that causes the common cold could emerge to cause a global pandemic, but that is our reality today. Here, I provide a basic-level scenic tour of the science behind SARS-CoV-2, the coronavirus that causes COVID-19 and its potential Achilles’ heels for use to develop therapies and cures.
Genetic testing has traced the origins of SARS-CoV-2 to horseshoe bats. Horseshoe bats and pangolins are wild animals that are consumed as delicacies in China. It is believed that close proximity of these animals in a food market in Wuhan, China provided the springboard for the virus to jump species from bat to pangolin, and from there, to its first human hosts.
SARS and MERS coronaviruses, also traced to animals as their natural hosts, caused the first fatal coronavirus outbreaks in 2003 and 2012, respectively. These outbreaks had overall fatality rates of approximately 10 percent and 34 percent, respectively. The current outbreak has a lower fatality rate but it is more contagious. According to John’s Hopkins University, the global death toll for COVID-19 stands at 171,810 with 2,501,156 confirmed infected individuals as of this writing on April 21, 2020. New York City accounts for 14,604 of these deaths, or 8.5 percent.
It is estimated that a natural extinguishing of the outbreak may begin to set in once at least half of the population is infected and becomes naturally immune, a concept referred to as “herd immunity.” In the meantime, numerous research, biotech and pharmaceutical laboratories, including my own, are working against time to develop vaccines and therapeutics. The biology of the virus and these efforts based upon it are described, below.
Briefly, SARS-CoV-2 coronaviruses are like little bubbles of grease with each particle made up of a thin, fatty outer envelope that, like a layer of skin, surrounds an inner genetic core. Infected persons shed viral particles directly into the air simply by the act of normal breathing. When inhaled by someone who is healthy, spike-like structures (called Spike proteins) that protrude from the viral particles bind to cells that line the individual’s respiratory tract. The virus fuses with these cells and empties its genetic core into them. The virus then takes command of the cell and uses its machinery like a factory to produce thousands of new viral particles. In the final step of the viral life-cycle, the new viral particles bud off the infected cell and go on to infect ever more cells. In severe cases, the lungs become severely damaged and vital lung functions like breathing and the supplying of oxygen to the body are destroyed.
Right here in our own backyard, Northwell Health is signing up those who have recovered from COVID-19 for its Convalescent Coronavirus Patient Registry. In addition to using antibodies generated by the immune response of those already exposed to SARS-CoV-2 as a potential COVID-19 therapy, at least 115 candidate vaccines are currently being pursued around the world. Here, various non-infectious forms of the virus or its components are provided to healthy subjects to prime the body’s immune system against a future challenge by live SARS-CoV-2. Countless brave and healthy volunteers will be needed for numerous vaccine trials to identify the safest and most effective vaccines that must then be scaled up for worldwide use.
On the therapeutics front, a number of known drugs are currently being investigated in clinical trials to determine if any existing prove effective against COVID-19, including Hydroxychloroquine and Azithromycin. In addition, efforts are underway to discover novel drug candidates directed to various stages of the SARS-CoV-2 life-cycle. The development of new drugs is a long and risky process that normally takes eight to 12 years or more at an average cost of billions of dollars. Northwell Health is pursuing clinical trials with Gilead Sciences to test the antiviral drug Remdesivir and with Regeneron and Sanofi to test Sarilumab, an antibody being investigated for possible amelioration of COVID-19 complications. My own biotechnology company, Chromocell Corporation, is exploring the re-purposing of its ENaC-modulating compounds, currently commercialized in other applications, for possible use to help clear excess fluid in the COVID-19 lung.
Many ideas must be tested to find winning formulas, and as my mentor, the late Nobel laureate Günter Blobel, used to say, “Beautiful ideas can get destroyed by ugly facts.” That said, some of the world’s best, brightest and most creative scientists, physicians, clinicians, research institutions and hospitals right here in New York City and around the world have joined the effort. Thanks to decades of breakthrough advances, we have an incredible tool chest of cutting-edge technologies, instrumentation, analytics and research and clinical infrastructures and capabilities. Unlike the coronavirus curve, the curve of biomedical innovation has never been flattened. The scientific world is as ready as it could ever be to rise up to the coronaviral challenge.
Kambiz Shekdar, Ph.D. is a biologist, a biotech inventor, co-founder of Chromocell Corporation, gay man, and president of Research Foundation to Cure AIDS (RFTCA). Contact kambiz.shekdar@rftca.org to inquire about joining RFTCA’s founders’ circle.
