Developmental Biology - COVID 19|
Developing A New System Combatting COVID-19
A system that can be used for other viruses as well...
A multidisciplinary team at The University of Texas Medical Branch at Galveston working to combat the COVID-19 virus has a system that will unlock researchers' ability to more quickly develop and evaluate developing vaccines, diagnose infected patients and explore whether or how the virus has evolved.
The scientists, led by Pei-Yong Shi, developed the system by engineering a reverse genetic system for SARS coronavirus 2, or SARS-CoV-2, that is causing the current COVID-19 pandemic. The study is currently available in Cell Host & Microbe.
A Reverse genetic system is one of the most useful tools for studying and combatting viruses. The system allows researchers to make the virus in the lab and manipulate it in a petri dish. Using this system, the UTMB team has engineered a version of the SARS-CoV-2 virus that is labeled with neon green. When the labeled virus infects a cell, the infected cell turns green.
"The labeled virus could be used to rapidly determine whether a patient has already been infected by the new coronavirus or evaluate how well developing vaccines are inducing antibodies that block infection of the virus. The level of antibodies induced by a vaccine is the most important parameter in predicting how well a vaccine works," said Shi, I.H. Kempner professor of Human Genetics at UTMB. "The neon green labeled virus system allows us to test patients' samples in 12 hours in a high-throughput manner that tests many samples at once. In contrast, the conventional method can only test a few specimens at a time with a long turnaround time of a week."
"This technology can significantly reduce how long it takes to evaluate developing vaccines and ultimately bring them to the market. UTMB will be very happy to make this technology widely available to both academia and industry researchers working to quickly develop countermeasures."
Xuping Xie PhD, Research Scientist, Designer and Developer of the Genetic System, University of Texas, Medical Branch, USA.
"The genetic system allows us to study the evolution of the new coronavirus. This will help us to understand how the virus jumped from its original host bat species to humans. It remains to be determined if an intermediate host is required for the host switch from the original bats to humans for the new coronavirus," said Vineet Menachery, Assistant Professor at UTMB, who co-senior-authored the study. "The system has provided a critical tool for the research community."
"This is another example of team science at UTMB," said Dr. Ben Raimer, President ad Interim of UTMB. "The collective effort from teams with complementary expertise worked together to deliver this exciting study. We will expand the team science to areas of clinical care and patient diagnosis by deploying the technology for serological testing."
"This will not be the last emerging virus that plagues humanity. In the past two decades, we've seen other coronaviruses like SARS and MERS, as well as other viruses like Zika, Ebola and others.
It's critically important to have a system that can be used for any new future or re-emerging viruses so that we can very quickly respond to the pathogens and protect peoples' health."
Pei-Yong Shi PhD, I.H. Kempner professor of Human Genetics, University of Texas, Medical Branch, USA.
The ongoing pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the urgency to develop experimental systems for studying this virus and identifying countermeasures. We report a reverse genetic system for SARS-CoV-2.
Seven cDNA fragments spanning the SARS-CoV-2 genome were assembled into a full-genome cDNA. RNA transcribed from the full-genome cDNA was highly infectious after electroporation
into cells, producing 2.9×106 PFU/ml of virus. Compared with a clinical isolate, the infectious clone-derived SARS-CoV-2 (icSARS-CoV-2) exhibited similar plaque morphology, viral RNA profile, and replication kinetics. Additionally, icSARS-CoV-2 retained engineered molecular markers and did not acquire other mutations. A stable mNeonGreen SARS-CoV-2 (icSARS-CoV-2-mNG) was generated by introducing this reporter gene into OFR7 of the viral genome. icSARSCoV-2-mNG was successfully used to evaluate the antiviral activities of interferon. Collectively, the reverse genetic system and reporter virus provide key reagents to study SARS-CoV-2 and develop countermeasures
Xuping Xie, Antonio Muruato, Kumari G. Lokugamage, Krishna Narayanan, Xianwen Zhang, Jing Zou, Jianying Liu, Craig Schindewolf, Nathen E. Bopp, Patricia V. Aguilar, Kenneth S. Plante, Scott C. Weaver, Shinji Makino, James W. LeDuc, Vineet D. Menachery and Pei-Yong Shi. Other authors include UTMB's Antonio Muruato, Kumari Lokugamage, Krishna Narayanan, Xianwen Zhang, Jing Zou, Jianying Liu, Craig Schindewolf, Nathen Bopp, Patricia Aguilar, Kenneth Plante, Scott Weaver, Shinji Makino and James LeDuc.
The authors thank Natalie Thornburg and other colleagues from the Centers for Disease Control and Prevention for providing the clinical virus isolate. We also thank colleagues at UTMB for support 199 and discussions.
Research was supported by grants from NIA and NIAID of the NIH 200 (U19AI100625 and R00AG049092 to V.D.M.; R24AI120942 (WRCEVA) to S.C.W.; AI114657 and AI146081 to S.M.; 5UC7AI094660 to J.W.L.). Research was also supported by STARs Award provided by the University of Texas System to V.D.M., trainee funding provided by the McLaughlin Fellowship Fund at UTMB, and IHII Pilot grant to SM. P.-Y.S. was supported by NIH grants AI142759, AI145617, AI127744, AI136126, and UL1TR001439, and awards from the Kleberg Foundation, John S. Dunn Foundation, Amon G. Carter Foundation, Gilson Longenbaugh 11 Foundation, and Summerfield Robert Foundation. A.M. is supported by a Clinical and Translational Science Award NRSA (TL1) Training Core (TL1TR001440) from NIH.
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Graphic representation of the reverse genetic system for SARS-CoV-2.
CREDIT The University of Texas Medical Branch at Galveston