Laos: SARS-CoV-2-related COVID virus derived from bats, can also infect human cells

SARS-CoV-2-related viruses have been found in bats in Laos that may enter human cells by connecting to the ACE2 receptor, indicating that the COVID-19 causing virus may have evolved from an animal reservoir in Asia, according to a study lead by researchers at the University of Paris.

"The animal reservoir of SARS-CoV-2 is unknown despite reports of various SARS-CoV-2-related viruses in Asian Rhinolophus bats, including the closest virus from R. affinis, RaTG13, and in pangolins," senior author Marc Eloit, a researcher at the Pasteur Institute and the University of Paris, and his colleagues explained in a paper published in Nature on Wednesday.

The researchers further added that SARS-CoV-2 progenitor bat viruses that can enter human cells via a human ACE2 route had not previously been identified. With this in mind, the researchers used a nested PCR screening approach to look for Coronavirus sequences in 247 blood, 608 saliva, 539 anal/fecal, and 157 urine swab samples from 645 bats caught in limestone caves at four locations in the Oudomxay province of northern Laos from the summer of 2020 to early 2021.

Coronavirus sequences were found in 24 bats from 10 different species, spanning 46 species and half a dozen bat families, according to the researchers. When the researchers compared the amplicons to viral database sequences, they discovered sequences that matched numerous known alphacoronaviruses and betacoronaviruses, as well as sequences from the same sarbecovirus subgenus as SARS-CoV and SARS-CoV-2.

Researchers discovered close genetic links between SARS-CoV-2

Researchers discovered close genetic links between SARS-CoV-2 and three of the viruses detected in insectivorous Rhinolophus bat species in Laos using whole-genome sequencing and phylogenetic studies centred on five sarbecoviruses. The mosaicism seen in SARS-CoV-2 and comparable viruses was explained using recombination breakpoint analysis.

Meanwhile, the researchers demonstrated that viruses that differed from SARS-CoV-2 at one or two amino acid residues in the receptor-binding domain of the spike protein could enter human cells via the ACE2 protein and replicate in them, processes that were inhibited by the addition of SARS-CoV-2 neutralising antibodies.

The newly discovered sarbecoviruses appeared to be as good as or better at binding the ACE2 receptor protein than the SARS-CoV-2 strain first identified in Wuhan, China, according to the researchers, despite the fact that they all lack a furin cleavage binding site found in the SARS-CoV-2 RBD.

Further, researchers from the University of Texas Medical Branch and their colleagues published a study in Nature in early 2021 showing that a version of SARS-CoV-2 lacking the furin site could replicate in hamster and transgenic mouse models, but that it appeared to protect these animals from severe disease when they were later exposed to wild-type versions of SARS-CoV-2.

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