The coronavirus is a master of camouflage - and San Antonio scientists caught it in the act
Lead investigator Yogesh Gupta works in his lab at UT Health San Antonio’s Greehey Children's Cancer Research Institute. His research team discovered how coronaviruses are able to evade our immune defenses by using changes in metal ions. Could new treatments for hospitalized COVID-19 patients emerge from San Antonio? Scientists at four local research institutions have laid the groundwork for such discoveries with a study that showed how coronaviruses such as SARS-CoV-2 can hide in the body and circumvent our immune defenses. It turns out that the virus camouflages itself by exploiting changes in metal ions — positively charged atoms such as magnesium, manganese and calcium. Varying concentrations of metal ions have been observed in hospitalized COVID-19 patients. Lead investigator Yogesh Gupta, an assistant professor of biochemistry and structural biology at UT Health San Antonio, says that by studying how this mechanism works, scientists may be able to develop effective therapies to treat coronavirus infections. The research also involved experts from the Texas Biomedical Research Institute, the University of Texas at San Antonio and the Southwest Research Institute. It was published this month in the journal Nature Communications . Lead investigator Yogesh Gupta, at UT Health San Antonio, says that by studying how the virus camouflages itself, scientists may be able to develop effective therapies to treat coronavirus infections. “What we do is we isolate the virus’s proteins and RNA, assemble it, crystallize it in our lab and then send those crystals to a national laboratory, where we have very sophisticated instruments called synchrotrons to measure high-resolution X-ray diffraction data,” said Gupta, who has a lab at the Greehey Children’s Cancer Research Institute at UT Health San Antonio. Gupta said the samples were sent to the U.S. Department of Energy’s Advanced Photon Source at Argonne National Laboratory outside Chicago. The researchers used the equipment remotely to capture atomic-level snapshots of the virus during its camouflaging process. Then the team solved and studied the three-dimensional structures of viral protein-mRNA complexes in their San Antonio lab. Gupta says the metal ions have an architectural purpose: They form a bridge between viral messenger RNA (which carries instructions for encoding the virus) and a protein complex consisting of viral proteins nsp16 and nsp10. Imagine a scaffold swaying in the wind and workers using their hands to steady it. With this “scaffold” stabilized by the ions, the virus uses nsp16 to modify its messenger RNA cap, so it is unrecognizable to the immune system. The COVID-19 pandemic has caused the deaths of an estimated 3.7 million people, according to the World Health Organization . In Bexar County , at least 3,489 people have died from COVID-19. This project was one of several funded by the San Antonio Partnership for Precision Therapeutics, which was created to boost the work of local scientists with research grants and is funded by the city’s four major research institutions. Liz Tullis, the partnership’s executive director, said it has provided $1.6 million for seven projects, including Gupta’s. The partnership is reviewing proposals from research teams to study the long-term impact of COVID-19. Those awards will be announced next month.