Is a New SARS-like Virus on the Horizon?

Researchers at the University of North Carolina (UNC)-Chapel Hill have identified what they describe as a new, “SARS-like” virus that will not need to adapt in order to infect humans.

Severe acute respiratory syndrome, or SARS, is caused by the SARS-coronavirus. In 2002-2003, an outbreak of SARS that started in southern China resulted in more than 8,000 reported cases globally, with nearly 800 fatalities. At the time, the virus was linked to animals sold in outdoor markets in China, primarily horseshoe bats.

For this study, the results of which were published on March 14 in the journal Proceedings of the National Academy of Sciences (PNAS), the UNC team led by Ralph S. Baric, PhD, Professor of Epidemiology at the university’s Gillings School of Public Health, reconstructed newly identified coronavirus sequences—which earlier research has identified as WIV1—isolated from Chinese horseshoe bats to assess their potential to infect both mice models and humans. Using the SARS-coronavirus infectious clone as a template, they “designed and synthesized a full-length infectious clone” of WIV1-coronavirus with six plasmids. They were able to “enzymatically cut, ligate, and electroporate” the clone into cells for replication. They also produced a WIV1-coronavirus “chimeric virus” within the mouse-adapted backbone (WIV1-MA15) that “incorporates the original binding and entry capabilities of WIV1-coronavirus, but maintains the backbone changes to mouse-adapted SARS-coronavirus” without the Y436H mutation in spike that is required for SARS-MA15 pathogenesis.

To confirm growth kinetics and replication, the UNC team infected Vero cells with SARS-coronavirus Urbani, WIV1-MA15, and WIV1-coronavirus, and found that each had similar replication kinetics and overall titers. Indeed, they determined that WIV1-coronavirus is capable of binding to the same receptors—human angiotensin converting enzyme (ACE2) orthologs—as SARS-coronavirus and that it can be “readily replicated” in cultured human airway tissue. Although their findings suggest that the new virus could be transmitted directly to humans, the authors believe it will require further adaptation to become an “epidemic disease.”

“[Our model provides] the opportunity to identify future threats for epidemics that are currently circulating in animal populations,” noted Vineet Menachery, PhD, lead author of the PNAS paper and a postdoctoral scholar at Gillings. “Significant efforts have been made to capture these viral sequences from animal sources around the world. The approach that we outlined extends this resource to examine the threat these viruses may pose in terms of ability to infect human cells, cause disease in mice, and the efficacy of the drugs/treatments. While we did this for SARS-like viruses, this approach could be expanded to other viral families and potentially help prevent or control a future outbreak.”

Their findings may also provide a template for managing an outbreak of WIV1-coronavirus should one occur. The research team focused on the potential role for monoclonal antibody therapies in this regard, starting with a SARS-coronavirus monoclonal derived via phage display and antibody escape and found that both wild-type SARS-coronavirus Urbani and WIV1-MA15 were “strongly neutralized at low antibody concentrations.” They noted that in earlier research a panel of monoclonal antibodies derived from B cells from SARS-infected patients also prevented virus infection via WIV1-coronavirus.

“The Ebola outbreak highlighted potential holes and problems with the public health infrastructure both in the US and around the world,” Dr. Menachery said. “As such, I believe we are better equipped to deal with future outbreaks. However, it is not clear where new outbreaks will come from and what we will know about them. For Ebola, MERS and Zika viruses, public investment in broad basic science provided the knowledge base for our responses. In my opinion, it is key to continue building on this broad basic science foundation to prepare for the next epidemic whose origins may be distinct from any previous outbreaks.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.