Researchers from the Institut Pasteur have identified three bat viruses in Laos that are the closest known relatives to SARS-CoV-2, surpassing all previously discovered pathogens. These findings strengthen the case for a natural origin of the COVID-19 pandemic and highlight evolving coronaviruses in wildlife that could pose risks to humans.
These discoveries are pivotal for understanding COVID-19's origins. Scientists at France's Institut Pasteur analyzed samples from bats and pinpointed three viruses closely related to SARS-CoV-2. Published on the Research Square preprint server, the study shows these viruses feature receptor-binding domains (RBDs) nearly identical to SARS-CoV-2's, enabling them to infect human cells via the ACE2 receptor.
The RBD, a key part of the spike protein, is what allows SARS-CoV-2 to latch onto and enter human cells through ACE2.
Marc Eloit and colleagues collected saliva, feces, and urine from 645 bats (Rhinolophus species) in northern Laos caves. These viruses—named BANAL-52, BANAL-103, and BANAL-236—share more than 95% identity with SARS-CoV-2.
Laboratory tests confirmed their RBDs bind to human ACE2 receptors as effectively as those in early SARS-CoV-2 variants.
"When SARS-CoV-2 was first sequenced, its receptor-binding domain was unlike anything we'd seen," notes Edward Holmes from the University of Sydney, Australia. "This fueled lab-origin speculation, but these Laos coronaviruses prove such features exist naturally."
"I'm more convinced than ever that SARS-CoV-2 has a natural origin," adds Linfa Wang, virologist at Duke-NUS Medical School in Singapore.
Building on prior finds in Thailand, China, and Cambodia, this research cements Southeast Asia as a hotspot for SARS-CoV-2-related coronavirus diversity.
While supporting a natural pandemic origin, gaps persist. Notably, the Laos viruses lack SARS-CoV-2's furin cleavage site on the spike protein, which enhances human cell entry.
Marc Eloit offers potential explanations: "A non-pathogenic virus may have circulated in humans first and mutated, or a close relative with the furin site awaits discovery."
