Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine DOI Creative Commons
Peter Halfmann, Kathryn Loeffler, Augustine Duffy

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 12, 2024

Abstract The 2002 SARS outbreak, the 2019 emergence of COVID-19, and continuing evolution immune-evading SARS-CoV-2 variants together highlight need for a broadly protective vaccine against ACE2-utilizing sarbecoviruses. While updated variant-matched formulations are step in right direction, protection needs to extend beyond its include SARS-like viruses. Here, we introduce bivalent trivalent using our spike protein nanoparticle platform that completely protect female hamsters BA.5 XBB.1 challenges with no detectable virus lungs. cocktails elicit highly neutralizing responses all tested Omicron bat sarbecoviruses SHC014 WIV1. Finally, 614D/SHC014/XBB formulation protects human ACE2-transgenic WIV1 Collectively, these results illustrate protein-nanoparticle cocktail can provide broad SARS-CoV-2-like SARS-CoV-1-like

Language: Английский

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2 DOI Creative Commons
Jonathan E. Pekar, Andrew F. Magee, Edyth Parker

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6609), P. 960 - 966

Published: July 26, 2022

Understanding the circumstances that lead to pandemics is important for their prevention. We analyzed genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in disease 2019 (COVID-19) pandemic. show SARS-CoV-2 before February 2020 likely comprised only two distinct viral lineages, denoted "A" and "B." Phylodynamic rooting methods, coupled with epidemic simulations, reveal these lineages were result at least separate cross-species transmission events into humans. The first zoonotic involved lineage B viruses around 18 November (23 October 8 December), introduction A occurred within weeks this event. These findings indicate it unlikely circulated widely humans define narrow window between when jumped cases COVID-19 reported. As other coronaviruses, emergence resulted from multiple events.

Language: Английский

Citations

202

The Evolution and Biology of SARS-CoV-2 Variants DOI Open Access
Amalio Telenti, Emma B. Hodcroft, David L. Robertson

et al.

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2022, Volume and Issue: 12(5), P. a041390 - a041390

Published: April 20, 2022

Our understanding of the still unfolding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic would have been extremely limited without study genetics and evolution this new human coronavirus. Large-scale genome-sequencing efforts provided close to real-time tracking global spread diversification SARS-CoV-2 since its entry into population in late 2019. These data underpinned analysis origins, epidemiology, adaptations population: principally immune evasion increasing transmissibility. SARS-CoV-2, despite being a pathogen, was highly capable human-to-human transmission. During rapid humans, has evolved independent forms, so-called "variants concern," that are better optimized for The most important adaptation bat progenitor both SARS-CoV-1 infection (and other mammals) is use angiotensin-converting enzyme (ACE2) receptor. Relaxed structural constraints provide plasticity SARS-related spike protein permitting it accommodate significant amino acid replacements antigenic consequence compromising ability bind ACE2. Although bulk research justifiably concentrated on viral as main determinant changes transmissibility, there accumulating evidence contribution regions proteome virus-host interaction. Whereas levels community transmission recombinants genetically distinct variants at present low, when divergent cocirculate, recombination between clades detected, risk viruses with properties emerge. Applying computational machine learning methods genome sequence sets generate experimentally verifiable predictions will serve an early warning system novel variant surveillance be future vaccine planning. Omicron, latest concern, focused attention step change events, "shift," opposed incremental "drift" antigenicity. Both increase transmissibility shift Omicron led readily causing infections fully vaccinated and/or previously infected. Omicron's virulence, while reduced relative concern replaced, Delta, very much premised past exposure individuals clear signal boosted vaccination protects from disease. Currently, proven itself dangerous pathogen unpredictable evolutionary capacity, leading too great not ensure all world screened by sequencing, protected through available affordable vaccines, non-punitive strategies place detecting responding concern.

Language: Английский

Citations

158

Exploring the Natural Origins of SARS-CoV-2 in the Light of Recombination DOI Creative Commons
Spyros Lytras, Joseph Hughes, Darren P. Martin

et al.

Genome Biology and Evolution, Journal Year: 2022, Volume and Issue: 14(2)

Published: Feb. 1, 2022

Abstract The lack of an identifiable intermediate host species for the proximal animal ancestor SARS-CoV-2, and large geographical distance between Wuhan where closest evolutionary related coronaviruses circulating in horseshoe bats (members Sarbecovirus subgenus) have been identified, is fueling speculation on natural origins SARS-CoV-2. We performed a comprehensive phylogenetic study SARS-CoV-2 all bat pangolin sarbecoviruses sampled so far. Determining likely recombination events reveals highly reticulate history within this group coronaviruses. Distribution inferred nonrandom with evidence that Spike, main target humoral immunity, beside hotspot driving antigenic shift ancestry sarbecoviruses. Coupled geographic ranges their hosts sampling locations, across southern China, into Southeast Asia, we confirm bats, Rhinolophus, are reservoir progenitor. By tracing recombinant sequence patterns, conclude there has relatively recent movement cocirculation these viruses’ ancestors, extending China Asia over last 100 years. direct to not yet sampled, since known relatives collected Yunnan shared common approximately 40 years ago. Our analysis highlights need dramatically more wildlife to: 1) pinpoint exact SARS-CoV-2’s progenitor, 2) facilitated transmission from humans (if one), 3) survey extent diversity sarbecoviruses’ phylogeny present high risk future spillovers.

Language: Английский

Citations

137

Individual bat virome analysis reveals co-infection and spillover among bats and virus zoonotic potential DOI Creative Commons
Jing Wang, Yuanfei Pan,

Lifen Yang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 10, 2023

Abstract Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within individual bats, hence frequency virus co-infection spillover among them. We characterize mammal-associated in 149 bats sampled from Yunnan province, China, using an unbiased meta-transcriptomics approach. This reveals a high (simultaneous infection bat individuals by multiple viral species) animals studied, which may turn facilitate recombination reassortment. Of note, we identify five species that likely to be pathogenic humans or livestock, based on phylogenetic relatedness pathogens vitro receptor binding assays. includes novel recombinant SARS-like coronavirus closely related both SARS-CoV SARS-CoV-2. In assays indicate this can utilize human ACE2 such it increased emergence risk. Our study highlights common occurrence their implications emergence.

Language: Английский

Citations

66

Host traits shape virome composition and virus transmission in wild small mammals DOI Creative Commons
Yanmei Chen,

Shu-Jian Hu,

Xian‐Dan Lin

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(21), P. 4662 - 4675.e12

Published: Sept. 20, 2023

Language: Английский

Citations

61

Surveillance of SARS-CoV-2 at the Huanan Seafood Market DOI Open Access

William J. Liu,

Peipei Liu,

Wenwen Lei

et al.

Nature, Journal Year: 2023, Volume and Issue: 631(8020), P. 402 - 408

Published: April 5, 2023

Language: Английский

Citations

57

Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines DOI Creative Commons

Liyan Guo,

Sheng Lin, Zimin Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 10, 2023

Abstract The ongoing global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS‐CoV‐2), has devastating impacts on the public health and economy. Rapid viral antigenic evolution led to continual generation new variants. Of special note is recently expanding Omicron subvariants that are capable immune evasion from most existing neutralizing antibodies (nAbs). This posed challenges for prevention treatment COVID-19. Therefore, exploring broad-spectrum antiviral agents combat emerging variants imperative. In sharp contrast massive accumulation mutations within SARS-CoV-2 receptor-binding domain (RBD), S2 fusion subunit remained highly conserved among Hence, S2-based therapeutics may provide effective cross-protection against Here, we summarize developed inhibitors (e.g., nAbs, peptides, proteins, small-molecule compounds) candidate vaccines targeting elements in subunit. main focus includes all targetable elements, namely, peptide, stem helix, heptad repeats 1 (HR1-HR2) bundle. Moreover, a detailed summary characteristics action-mechanisms each class cross-reactive inhibitors, which should guide promote future design coronaviruses.

Language: Английский

Citations

48

The Emergence and Evolution of SARS-CoV-2 DOI
Edward C. Holmes

Annual Review of Virology, Journal Year: 2024, Volume and Issue: 11(1), P. 21 - 42

Published: April 18, 2024

The origin of SARS-CoV-2 has evoked heated debate and strong accusations, yet seemingly little resolution. I review the scientific evidence on its subsequent spread through human population. available data clearly point to a natural zoonotic emergence within, or closely linked to, Huanan Seafood Wholesale Market in Wuhan. There is no direct linking laboratory work conducted at Wuhan Institute Virology. global was characterized by gradual adaptation humans, with dual increases transmissibility virulence until Omicron variant. Of note been frequent transmission from humans other animals, marking it as strongly host generalist virus. Unless lessons are learned, inevitable that more events leading epidemics pandemics will plague populations.

Language: Английский

Citations

32

Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic DOI

Alexander Crits‐Christoph,

Joshua I. Levy, Jonathan E. Pekar

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5468 - 5482.e11

Published: Sept. 1, 2024

Language: Английский

Citations

28

Bat-infecting merbecovirus HKU5-CoV lineage 2 can use human ACE2 as a cell entry receptor DOI
Jing Chen, Wei Zhang, Yang Li

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

6