Coronaviruses with a SARS-CoV-2-like receptor-binding domain allowing ACE2-mediated entry into human cells isolated from bats of Indochinese peninsula

Abstract

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. Several studies have suggested the involvement of pangolin coronaviruses in SARS-CoV-2 emergence. SARS-CoV-2 presents a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain (RBD) to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range. SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 pathway have not yet been identified, though they would be key in understanding the origin of the epidemics. Here we show that such viruses indeed circulate in cave bats living in the limestone karstic terrain in North Laos, within the Indochinese peninsula. We found that the RBDs of these viruses differ from that of SARS-CoV-2 by only one or two residues, bind as efficiently to the hACE2 protein as the SARS-CoV-2 Wuhan strain isolated in early human cases, and mediate hACE2-dependent entry into human cells, which is inhibited by antibodies neutralizing SARS-CoV-2. None of these bat viruses harbors a furin cleavage site in the spike. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.

Interspecies Jumping of Bat Coronaviruses

“…Such an insertion allows the SASRS-CoV-2 S protein to undergo proteolytic cleavage, resulting in cell-cell fusion enhancement and contributes to pathogenesis [31,[156][157][158]. It is of note that the additional cleavage site in the S gene has not been observed in any bat SARSr-CoV strains discovered so far since 2003, including those recently discovered in southeast Asia [155,[159][160][161][162][163], nor in any pangolin SARS-CoV-2 strains [153,154,161]. This has raised concerns in both the scientific community and the general public globally, pending further research into its possible origin.…”

“…Shortly after the beginning of the pandemic, two independent groups have found in their surveillance studies that SARSr-CoVs were detected in pangolins in the Guangdong province of southern China and that the RBD region of the S protein in SARS-CoV-2 shares the closest relationship (~97% amino acid identity) with those observed in these pangolin SARSr-CoVs [153,154]. In addition, a recent pre-print research article has described the discovery of a bat SARSr-CoV strain BANAL-20-52 from the Indochinese peninsula, which also carries an RBD region with ~97% amino acid identity to that of SARS-CoV-2 [155].…”

Zoonotic disease and virome diversity in bats

“…Astroviridae , Reoviridae and Picornaviridae ) ( Figure 2 ). As a case in point, a range of SARS-CoV-2 related coronaviruses have been characterised through mNGS of bats sampled in China and parts of south-east Asia [ 19 •• , 20 , 21 ]. The viruses carried by bats also vary markedly by bat family ( Figure 2 ).…”

“…SARS-CoV-2 was first reported to cause severe pneumonia in humans in Wuhan, China in late 2019 [ 33 • ]. Metagenomic surveys and associated phylogenetic analyses have identified viruses closely related to SARS-CoV-2 in Rhinolophus bat species from several Asian countries (China, Cambodia, Thailand, Japan and Laos) [ 19 •• , 20 , 21 , 34 , 35 • , 36 ]. For example, five SARS-CoV-2 related coronaviruses were detected in pooled faecal samples collected from bats ( Rhinolophus pusillus, Rhinolophus stheno and Rhinolophus malayanus ) in two studies of a single tropical botanical garden in Yunnan province, China [ 19 •• , 20 ].…”

Coronavirus Pandemics Era and Cancer Patients

“…There are more and more studies that establish that viruses similar to the coronavirus (SARS) can be transmitted from animals to people hundreds of thousands of times a year, facilitating new adaptations in humans and therefore the development of pandemics 1 . Recently, a work under review based on samples from the Indochinese peninsula, concludes that these viruses can move rapidly in wide geographic ranges in bat reservoirs, frequently infecting people who work in caves, such as guano collectors, or certain ascetic religious communities who spend time in or very close to caves, as well as tourists who visit caves, at particular risk of exposure 2 . In addition, it must be considered that it will also depend on the evolution of the SARS-CoV-2 (COVID- 19) variants associated with global vaccination campaigns in order to maintain the efficacy of current vaccines 3 .…”