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1.
Nature ; 604(7905): 330-336, 2022 04.
Article in English | MEDLINE | ID: covidwho-1692583

ABSTRACT

The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV-2-related viruses in Asian Rhinolophus bats1-4, including the closest virus from R. affinis, RaTG13 (refs. 5,6), and pangolins7-9. SARS-CoV-2 has a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range10-12. SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 (hACE2) pathway have not yet been identified, although they would be key in understanding the origin of the epidemic. Here we show that such viruses circulate in cave bats living in the limestone karstic terrain in northern Laos, in the Indochinese peninsula. We found that the receptor-binding domains of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2, bind more efficiently to the hACE2 protein than that of the SARS-CoV-2 strain isolated in Wuhan from early human cases, and mediate hACE2-dependent entry and replication in human cells, which is inhibited by antibodies that neutralize SARS-CoV-2. None of these bat viruses contains a furin cleavage site in the spike protein. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses that are potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.


Subject(s)
COVID-19 , Chiroptera , Angiotensin-Converting Enzyme 2 , Animals , Asia , Caves , Chiroptera/virology , Disease Reservoirs , Humans , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323389

ABSTRACT

Background: Lao PDR has low reported COVID-19 cases but it is unclear whether this masks silent transmission. A nationwide seroprevalence study was done between August and September 2020 to determine SARS-CoV-2 exposure.Methods: Participants were from the general community/healthcare workers in five provinces. Bat/wildlife contacts were from Vientiane province. ELISAs detected anti-Nucleoprotein (N;n=3173 tested) and anti-Spike (S;n=1417 tested) SARS-CoV-2 antibodies. Double-positive samples were checked by IgM/IgG rapid tests. Positive controls were confirmed COVID-19 cases and negative controls were pre-COVID-19 samples.Findings: In pre-COVID-19 samples, 14/265 (5·3%, [95% CI=3·1-8·7%]) were anti-N antibody single-positive and 3/265 (1·1% [0·3-3·5%]) were anti-S antibody single positive. None were anti-N and anti-S antibody double positive. Anti-N and anti-S antibodies were detected in 131/2417 (5·4% [4·5-6·3%]) and 19/1061 (1·8% [1·1-2·8%]) of the general population, 13/666 (2·0% [1·1-3·3%]) and 4/282 (1·4% [0·5-3·7%]) of healthcare workers and 15/74 (20·3% [12·6-31·0%]) and 5/74 (6·8% [2·8-15·3%]) of bat/wildlife contacts. Only 2/3173 (0·1% [0·02-0·3%]) were double positive for anti-N and anti-S antibodies (rapid test negative).Interpretation: We find no evidence for significant circulation of SARS-CoV-2 in Lao PDR during or before September 2020. This likely results from decisive measures taken by the government early in the pandemic, social behavior, and low population density. High anti-N antibodies/low anti-S antibodies in bat/wildlife contacts may indicate exposure to cross-reactive animal coronaviruses with threat of emerging novel viruses.Funding: Core;Agence Française de Développement. Additional support;Institut Pasteur du Laos, Institute Pasteur, Paris and Luxembourg Ministry of Foreign and European Affairs (“PaReCIDS II”). Declaration of Interests: The authors have no conflict of interest to declare.Ethics Approval Statement: The study protocol was approved by all participating institutes and by the Lao National Ethics Committee for Health Research (NECHR) (Ref #052/2020).

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322622

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.

4.
Lancet Reg Health West Pac ; 13: 100197, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1309327

ABSTRACT

BACKGROUND: In 2020 Lao PDR had low reported COVID-19 cases but it was unclear whether this masked silent transmission. A seroprevalence study was done August - September 2020 to determine SARS-CoV-2 exposure. METHODS: Participants were from the general community (n=2433) or healthcare workers (n=666) in five provinces and bat/wildlife contacts (n=74) were from Vientiane province. ELISAs detected anti- SARS-CoV-2 Nucleoprotein (N; n=3173 tested) and Spike (S; n=1417 tested) antibodies. Double-positive samples were checked by IgM/IgG rapid tests. Controls were confirmed COVID-19 cases (n=15) and pre-COVID-19 samples (n=265). Seroprevalence for the general community was weighted to account for complex survey sample design, age and sex. FINDINGS: In pre-COVID-19 samples, 5·3%, [95% CI=3·1-8·7%] were anti-N antibody single-positive and 1·1% [0·3-3·5%] were anti-S antibody single positive. None were double positive. Anti-N and anti-S antibodies were detected in 5·2% [4·2-6·5%] and 2·1% [1·1-3·9%] of the general community, 2·0% [1·1-3·3%] and 1·4% [0·5-3·7%] of healthcare workers and 20·3% [12·6-31·0%] and 6·8% [2·8-15·3%] of bat/wildlife contacts. 0·1% [0·02-0·3%] were double positive for anti-N and anti-S antibodies (rapid test negative). INTERPRETATION: We find no evidence for significant SARS-CoV-2 circulation in Lao PDR before September 2020. This likely results from early decisive measures taken by the government, social behavior, and low population density. High anti-N /low anti-S seroprevalence in bat/wildlife contacts may indicate exposure to cross-reactive animal coronaviruses with threat of emerging novel viruses. FUNDING: Agence Française de Développement. Additional; Institut Pasteur du Laos, Institute Pasteur, Paris and Luxembourg Ministry of Foreign and European Affairs ("PaReCIDS II").

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