US and China-funded scientists in Wuhan lab studied coronavirus in bats for 5 years, and found lethal strains

Researchers from the CAS Key Laboratory of Special Pathogens and Biosafety at the Wuhan Institute of Virology in China spent five years studying severe acute respiratory syndrome (SARS) viruses found in multiple species of horseshoe bats that were living in a single cave in China's Yunnan Province. 

The cave was located approximately 60 km from the city of Kunming in China. The team found that "genetic recombination between viral strains in bats" may have produced the "direct evolutionary ancestor" of the strain that caused a deadly outbreak of SARS in humans, according to the 2017 study published in PLOS Pathogens. "This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases," concludes the research team from China and the US. 

Scientists say it is likely that the SARS-COV-2 virus, which causes the COVID-19 disease, was passed from bats to a mystery animal species that then passed it on to humans. There have been allegations that the COVID-19 virus escaped from a lab in Wuhan. Many scientists have, however, rubbished the rumors, stating that the deadly COVID-19 virus is not a bioweapon that escaped from a lab. An analysis by researchers from the Department of Immunology and Microbiology at Scripps Research, US, said the virus is a product of natural evolution.

Coronaviruses are a large family of viruses and the coronaviruses that can infect people are 229E (alpha coronavirus), NL63 (alpha coronavirus), OC43 (beta coronavirus) and HKU1 (beta coronavirus), says the CDC. The other human coronaviruses include MERS-CoV (the beta coronavirus that causes Middle East Respiratory Syndrome or MERS), SARS-CoV (the beta coronavirus that causes SARS) and SARS-CoV-2 (the novel coronavirus).

What did the researchers find?

In late 2002, a SARS epidemic broke out in southern China, ultimately killing hundreds of people in dozens of countries by the summer of 2003. Scientists traced the outbreak back to horseshoe bats, hypothesizing that the culprit, SARS coronavirus, originated in these animals and then spread either directly to humans or to animals that were later purchased by humans at markets.

However, the details of the outbreak's origin remained unclear. SARS strains found in bats are genetically distinct from the specific SARS strain that caused the outbreak, suggesting that known bat strains did not directly evolve into the outbreak strain. To address this issue, the research team spent five years studying SARS viruses found in horseshoe bats.

The 2017 study was jointly funded by Chinese and US agencies such as the National Natural Science Foundation of China, China Mega-Project for Infectious Disease, Scientific and technological basis special project from the Ministry of Science and Technology of China, the Strategic Priority Research Program of the Chinese Academy of Sciences, the National Institutes of Health (NIAID), and the USAID Emerging Pandemic Threats (EPT) PREDICT program, among others. 

The research institutes involved in the study are CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan; Yunnan Institute of Endemic Diseases Control and Prevention, Dali, China; Dali University, China; EcoHealth Alliance, New York, US; and Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.

The study says all sampling procedures were performed by veterinarians with approval from the Animal Ethics Committee of the Wuhan Institute of Virology. Bat samplings were conducted 10 times from April 2011 to October 2015 at different seasons in their natural habitat at a single location in Yunnan.

“We have carried out a five-year longitudinal surveillance on SARS-related coronaviruses (SARSr-CoVs) in bats from a single habitat in proximity to Kunming city, Yunnan province, China, which was mainly inhabited by horseshoe bats. A total of 602 alimentary specimens (anal swabs or feces) were collected and tested for the presence of CoVs. All members of field teams wore appropriate personal protective equipment, including N95 masks, tear-resistant gloves, disposable outerwear, and safety glasses. Bats were trapped and fecal swab samples were collected," says the study.

The research team identified 11 new strains of the SARS virus and sequenced their full genomes to uncover their evolutionary relationships. Genome analysis revealed that the newly-identified bat strains, as well as several strains identified in a previous study of the same bat cave, contained all the essential genetic building blocks of the human SARS coronavirus. In some of the strains, for instance, portions of a gene known as the S gene showed high genetic similarity to the same regions found in the SARS coronavirus genome.

Based on their genetic analysis, the researchers hypothesize that genetic recombination between precursor strains that later evolved into the newly-identified strains may also have given rise to a strain that directly evolved into SARS coronavirus.

"It is noteworthy that SARSr-CoVs detected in Yunnan are more closely related to SARS-CoV than strains from other regions in China. This finding implies that Yunnan, or southwestern China, is more likely to be the geographical source of SARS-CoV than other regions in China, but data from more extensive surveillance are yet needed to support this inference," the researchers say in their findings. 

Additional lab experiments showed that some of the newly-identified bat strains are capable of entering human cells via the same cellular receptor employed by SARS coronavirus. This suggests that the bat cave contains strains that could potentially be directly transmitted to humans, say experts. 

"In addition, we have also revealed that various SARSr-CoVs capable of using human ACE2 (the receptor of SARS-CoV in humans) are still circulating among bats in this region. Thus, the risk of spillover into people and emergence of a disease similar to SARS is possible," the researchers warn.

“This is particularly important given that the nearest village to the bat cave we surveyed is only 1.1 km away, which indicates a potential risk of exposure to bats for the local residents. Thus, we propose that monitoring of SARSr-CoV evolution at this and other sites should continue, as well as an examination of human behavioral risk for infection and serological surveys of people, to determine if spillover is already occurring at these sites and to design intervention strategies to avoid future disease emergence,” says the team.

Another bat study by Wuhan lab

In a 2018 study, researchers found that a newly identified coronavirus — that killed nearly 25,000 piglets in 2016-17 in China — had emerged from horseshoe bats near the origin of the severe acute respiratory syndrome coronavirus (SARS-CoV). The study investigators identified SADS-CoV on four pig farms in China's Guangdong Province.

The work was a collaboration among scientists from EcoHealth Alliance, Duke-NUS Medical School, Wuhan Institute of Virology and other organizations. It was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. 

The study says that the new virus, named swine acute diarrhea syndrome coronavirus (SADS-CoV), does not appear to infect people, unlike SARS-CoV. The researchers, however, say the finding is an important reminder that identifying new viruses in animals and quickly determining their potential to infect people is a key way to reduce global health threats.

SADS-CoV began killing piglets on a farm near Foshan in Guangdong Province in late October 2016. Investigators initially suspected porcine epidemic diarrhea virus (PEDV) as the cause. Detection of PEDV stopped ceased by mid-January 2017, yet piglets continued to die, suggesting a different cause. 

The investigators confirmed the connection of SADS-CoV to bats by identifying the new virus in the small intestine of piglets from the outbreak. They then determined that the genetic sequence of SADS-CoV is similar to that of a bat coronavirus discovered in 2007 and looked for evidence of SADS-CoV in bat specimens collected from 2013 to 2016 in Guangdong Province. The new virus appeared in 71 of 596 specimens (11.9%), says the study published in the journal Nature. The researchers also tested 35 farm workers who had close contact with sick pigs, none of which tested positive for SADS-CoV.