Phylogeographic evolution of horseshoe bat sarbecoviruses in Vietnam and implications for the origins of SARS-CoV and SARS-CoV-2

Abstract

Previous studies on horseshoe bats (Rhinolophus spp.) have described many coronaviruses related to SARS-CoV (SARSCoVr) in China and only a few coronaviruses related to SARS-CoV-2 (SARSCoV2r) in Yunnan, Cambodia, Laos and Thailand. Here, we report the results of several field missions carried out in 2017, 2021 and 2022 across Vietnam during which 1,218 horseshoe bats were sampled. We assemble 38 Sarbecovirus genomes: 26 SARSCoVr from R. thomasi; six SARSCoVr and four SARSCoV2r from R. affinis; and two recombinants of SARSCoVr and SARSCoV2r from R. pusillus, one showing a receptor-binding domain of the Spike protein very similar to SARS-CoV-2. We detected a bat co-infected with four coronaviruses, including two sarbecoviruses. Our phylogeographic analysis suggests a divergent evolution between sarbecoviruses from subtropical northern Vietnam and those from tropical southern Vietnam, emergence of SARS-CoV in horseshoe bats from northern Yunnan and emergence of SARS-CoV-2 in horseshoe bats from southern Yunnan.

Virological characteristics of a SARS-CoV-2-related bat coronavirus, BANAL-20-236

“…The origin of SARS-CoV-2 is an issue in the field of virology. Importantly, the discovery of SARS-CoV-2-related coronaviruses (SC2r-CoVs) in feces or rectal swabs of horseshoe bats (genus Rhinolophus ) (e.g., RaTG13, 6 RmYN02, 7 RacCS203, 8 RpYN06, 9 RshSTT182, 10 Rc-o319, 11 Rp22DB159 12 ) provided evidence supporting that SARS-CoV-2 originated from the zoonotic transmission of certain SC2r-CoV into the human population. A clear difference between SARS-CoV-2 and SC2r-CoVs is the presence of the furin cleavage site (FCS) only in the spike (S) protein of SARS-CoV-2.…”

SARS-CoV-2 isolates missing part of the furin cleavage site

“…The discovery of bat coronaviruses (sarbecoviruses) in Southeast Asia very similar to SARS-CoV-2 (1,2) is key to deciphering SARS-CoV-2's origin. They are remarkable the Rhinolophus malayanus BANAL52 isolate from Laos (1) and the Rhinolophus pusillus Rp22DB159 isolate from Vietnam (2) which are the closest known relatives of SARS-CoV-2.…”

“…In general, direct contact between humans and bats is limited, and an intermediate species often plays a role in the transmission of emerging viruses from bats to humans (3), however, several studies have recently concluded that SARS-CoV-2 emerged directly from a bat virus (1,2). Bat Rhinolophus species circulating in Southeast Asian harbour a diversity of coronaviruses (e.g., BANAL52, Rp22DB159) capable of infecting very distant mammal species, including humans.…”

“…The discovery of bat coronaviruses (sarbecoviruses) in Southeast Asia very similar to SARS-CoV-2 (1,2) is key to deciphering SARS-CoV-2's origin. They are remarkable the Rhinolophus malayanus BANAL52 isolate from Laos (1) and the Rhinolophus pusillus Rp22DB159 isolate from Vietnam (2) which are the closest known relatives of SARS-CoV-2. The BANAL52 and Rp22DB159 spike glycorpotein angiotensin-converting enzyme 2 (ACE2) receptor binding domain is almost identical to that of SARS-CoV-2, they can therefore infect human cells, despite the absence of the polybasic furin cleavage motif (1,2).…”

SARS-CoV-2 XBB.1.16.20 lineage study sample: 21% shows a synonymous base substitution in the S gene arginine codons CGG–CGG encoding the S protein furin cleavage site

“…The infection of human cells by SARS-CoV-2 is greatly favoured by a positive region in the furin cleavage site at the S1/S2 junction of the viral spike glycoprotein (1)(2)(3)(4)(5). It has no analogy in other Becoronavirus sarbecoviruses, including the new discovered Laos and Vietnam bat coronaviruses closest known relatives to SARS-CoV-2 (6,7). The key evolutionary step leading to the pandemic virus was the acquisition in a progenitor of SARS-CoV-2 the S gene 12 nucleotide insert encoding the polybasic furin site (PRRA).…”