Emerging SARS-CoV-2 variants: Why, how, and what's next? DOI Creative Commons
Yu Chen, Qianyun Liu, Li Zhou

et al.

Cell Insight, Journal Year: 2022, Volume and Issue: 1(3), P. 100029 - 100029

Published: May 2, 2022

The emergence of the SARS-CoV-2 Omicron variant poses a striking threat to human society. More than 30 mutations in Spike protein severely compromised protective immunity elicited by either vaccination or prior infection. persistent viral evolutionary trajectory generates Omicron-associated lineages, such as BA.1 and BA.2. Moreover, virus recombination upon Delta co-infections has been reported lately, although impact remains be assessed. This minireview summarizes characteristics, evolution mutation control, immune evasion mechanisms variants, which will helpful for in-depth understanding variants policy-making related COVID-19 pandemic control.

Language: Английский

The rapid rise of SARS‐CoV‐2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants DOI Creative Commons
Danyi Ao, Xuemei He, Weiqi Hong

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(2)

Published: March 15, 2023

As the fifth variant of concern SARS-CoV-2 virus, Omicron (B.1.1.529) has quickly become dominant type among previous circulating variants worldwide. During wave, several subvariants have emerged, with some exhibiting greater infectivity and immune evasion, accounting for their fast spread across many countries. Recently, two subvariants, BQ.1 XBB lineages, including BQ.1.1, XBB.1, XBB.1.5, a global public health issue given ability to escape from therapeutic monoclonal antibodies herd immunity induced by prior coronavirus disease 2019 (COVID-19) vaccines, boosters, infection. In this respect, which been established harbor rare mutation F486P, demonstrates superior transmissibility compared other emerged as strain in This review provides comprehensive overview epidemiological features, spike mutations, evasion lineages. We expounded on mechanisms underlying mutations neutralizing vaccinated or convalescent COVID-19 individuals (mAbs) proposed strategies prevention against sublineages.

Language: Английский

Citations

109
Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA.2.75 DOI Creative Commons
Qian Wang, Sho Iketani, Zhiteng Li

et al.

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(11), P. 1512 - 1517.e4

Published: Sept. 6, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2.75 emerged recently and appears to be spreading. It has nine mutations in spike compared with the currently circulating BA.2, raising concerns that it may further evade vaccine-elicited therapeutic antibodies. We found moderately more neutralization resistant sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar BA.2.12.1 (1.1-fold), but sensitive BA.4/5 (0.6-fold). Relative showed heightened resistance class 1 3 monoclonal antibodies targeting spike-receptor-binding domain while gaining sensitivity Resistance was largely conferred by G446S R460K mutations. slightly (3.7-fold) bebtelovimab, a antibody potent activity against all subvariants. also exhibited higher binding affinity host receptor ACE2 other provides insight into SARS-CoV-2 evolution as gains transmissibility incrementally evading neutralization.

Language: Английский

Citations

99
Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins DOI Creative Commons
Youwei Xu, Canrong Wu, Xiaodan Cao

et al.

Cell Research, Journal Year: 2022, Volume and Issue: 32(7), P. 609 - 620

Published: May 31, 2022

Abstract The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies show that the spike trimer exhibits 11-fold and 2-fold higher potency in to human ACE2 than from wildtype (WT) BA.1 strains. structure of complexed with reveals all three receptor-binding domains (RBDs) are open conformation, ready for binding, thus providing basis increased infectivity strain. JMB2002, therapeutic antibody was shown efficiently inhibit BA.1, also shows potent neutralization activities against BA.2. In addition, both trimers able bind mouse high potency. contrast, WT binds well cat but not ACE2. structures bound reveal their affinity interactions. Together, these results suggest possible evolution pathway variants via human-cat-mouse-human circle, which could have important implications establishing an effective strategy combating SARS-CoV-2 viral infections.

Language: Английский

Citations

82
Small molecules in the treatment of COVID-19 DOI Creative Commons
Sibei Lei, Xiaohua Chen, Jieping Wu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 5, 2022

Abstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies economies. Until now, effective therapeutics against are in high demand. Along with our improved understanding the structure, function, pathogenic process SARS-CoV-2, many small molecules potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition viral proteins such as RdRp M pro , interference host enzymes including ACE2 proteases, blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, NLRP3 pathways, regarded feasible drug development. development treat achieved strategies, computer-aided lead compound design screening, natural product discovery, repurposing, combination therapy. Several representative remdesivir paxlovid proved or authorized emergency use countries. And candidates entered clinical-trial stage. Nevertheless, due epidemiological features variability issues it is necessary continue exploring novel COVID-19. This review discusses current findings for treatment. Moreover, their detailed mechanism action, chemical structures, preclinical clinical efficacies discussed.

Language: Английский

Citations

82
Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Subvariant BA.2 in a Single-Source Community Outbreak DOI Open Access
Vincent Chi‐Chung Cheng, Jonathan Daniel Ip,

Allen Wing Ho Chu

et al.

Clinical Infectious Diseases, Journal Year: 2022, Volume and Issue: 75(1), P. e44 - e49

Published: March 8, 2022

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant BA.2 sublineage has increased rapidly in Europe and Asia since January 2022. Here, we report the epidemiological genomic analysis of a large single-source outbreak housing estate. Methods We analyzed information on community (STY outbreak). performed whole viral genome sequencing using Oxford Nanopore MinION device. calculated doubling time within Results STY involved total 768 individuals as 5 February 2022, including 432 residents, visitors, or staff (56.3%) from single estate (KC Estate). at KC Estate had short 1.28 days (95% confidence interval: .560–1.935). was promptly controlled with lockdown 3 buildings Whole-genome for 133 patients outbreak, 106 residents Estate. All sequences belonged to sublineage, phylogenetic showed that these cluster together. unique mutation C12525T. Conclusions Our study highlights exceptionally high transmissibility Hong Kong, where stringent measures are implemented part elimination strategy. Continual surveillance is crucial monitoring emergence epidemiologically important sublineages.

Language: Английский

Citations

76
Bench-to-bedside: Innovation of small molecule anti-SARS-CoV-2 drugs in China DOI Open Access
Liyan Yang, Zhonglei Wang

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 257, P. 115503 - 115503

Published: May 18, 2023

Language: Английский

Citations

64
Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion DOI Creative Commons

Song Xue,

Yuru Han, Fan Wu

et al.

Protein & Cell, Journal Year: 2024, Volume and Issue: 15(6), P. 403 - 418

Published: March 4, 2024

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles. Point mutations, particularly those within receptor binding domain (RBD) spike (S) protein, lead to functional alteration both engagement monoclonal antibody (mAb) recognition. Here, we review data RBD point mutations possessed by major discuss their individual effects on ACE2 affinity immune evasion. Many single amino acid substitutions epitopes crucial for evasion capacity may conversely weaken affinity. However, this weakened effect could be largely compensated specific epistatic such as N501Y, thus maintaining overall protein all variants. The predominant direction evolution lies neither promoting nor evading mAb neutralization but a delicate balance between these two dimensions. Together, interprets how efficiently resist meanwhile is maintained, emphasizing significance comprehensive assessment mutations.

Language: Английский

Citations

25
Structural insights into the SARS-CoV-2 Omicron RBD-ACE2 interaction DOI Creative Commons
Jun Lan, Xinheng He,

Yifei Ren

et al.

Cell Research, Journal Year: 2022, Volume and Issue: 32(6), P. 593 - 595

Published: April 13, 2022

Language: Английский

Citations

66
Binding Interactions between Receptor-Binding Domain of Spike Protein and Human Angiotensin Converting Enzyme-2 in Omicron Variant DOI Creative Commons
Bahaa Jawad, Puja Adhikari, Rudolf Podgornik

et al.

The Journal of Physical Chemistry Letters, Journal Year: 2022, Volume and Issue: 13(17), P. 3915 - 3921

Published: April 28, 2022

The emergence of new SARS-CoV-2 Omicron variant concern (OV) has exacerbated the COVID-19 pandemic because a large number mutations in spike protein, particularly receptor-binding domain (RBD), resulting highly contagious and/or vaccine-resistant strains. Herein, we present systematic analysis based on detailed molecular dynamics (MD) simulations order to understand how OV RBD affect ACE2 binding. We show that binds more efficiently and tightly predominantly strong electrostatic interactions, thereby promoting increased infectivity transmissibility compared other Some are predicted antibody neutralization either through their role S-protein conformational changes, such as S371L, S373P, S375F, or changing its surface charge distribution, G339D, N440K, T478K, E484A. Other mutations, K417N, G446S, Y505H, decrease binding, whereas S447N, Q493R, G496S, Q498R, N501Y tend increase it.

Language: Английский

Citations

64
A broad and potent neutralization epitope in SARS-related coronaviruses DOI Creative Commons
Meng Yuan, Xueyong Zhu, Wanting He

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(29)

Published: June 29, 2022

Many neutralizing antibodies (nAbs) elicited to ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through natural infection and vaccination have reduced effectiveness SARS-CoV-2 variants. Here, we show that therapeutic antibody ADG20 is able neutralize variants of concern (VOCs) including Omicron (B.1.1.529) as well other SARS-related coronaviruses. We delineate the structural basis this relatively escape-resistant epitope extends from one end receptor binding site (RBS) into highly conserved CR3022 site. can then benefit high potency direct competition with ACE2 in more variable RBS interaction Importantly, are target generally a broad range VOCs, albeit against Omicron. Thus, vulnerable be exploited for design universal vaccines antibodies.

Language: Английский

Citations

61