Development of Broad-Spectrum Nanobodies for the Therapy and Diagnosis of SARS-CoV-2 and Its Multiple Variants DOI
Lei He, Qian Wu, Zhaoyong Zhang

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown

Published: June 26, 2024

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evaded the efficacy previously developed antibodies and vaccines, thus remaining a significant global public health threat. Therefore, it is imperative to develop additional that are capable neutralizing emerging variants. Nanobodies, as smallest functional single-domain antibodies, exhibit enhanced stability penetration ability, enabling them recognize numerous concealed epitopes inaccessible conventional antibodies. Herein, we constructed an immune library based on immunization alpaca with S1 subunit SARS-CoV-2 spike protein, from which two nanobodies, Nb1 Nb2, were selected using phage display technology for further characterization. Both binding residues residing within receptor-binding domain (RBD) region spike, exhibited high affinity toward subunit. Moreover, they displayed cross-neutralizing activity against both wild-type 10 ο variants, including BA.1, BA.2, BA.3, BA.5, BA.2.75, BF.7, BQ.1, EG.5.1, XBB.1.5, JN.1. Molecular modeling dynamics simulations predicted nanobodies interacted viral RBD through their complementarity determining 1 (CDR1) CDR2. These novel tools development therapeutic diagnostic countermeasures targeting variants potentially coronaviruses.

Language: Английский

Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5 DOI Creative Commons
Qian Wang, Yicheng Guo, Sho Iketani

et al.

Nature, Journal Year: 2022, Volume and Issue: 608(7923), P. 603 - 608

Published: July 5, 2022

Abstract SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States South Africa, respectively 1,2 . These new carrying further mutations their spike proteins raise concerns that they may evade neutralizing antibodies, thereby compromising efficacy of COVID-19 vaccines therapeutic monoclonals. We now report findings from a systematic antigenic analysis these surging subvariants. is only modestly (1.8-fold) more resistant sera vaccinated boosted individuals than BA.2. However, substantially (4.2-fold) thus likely lead vaccine breakthrough infections. Mutation at residue L452 found both facilitates escape some antibodies directed so-called class 2 3 regions receptor-binding domain The F486V mutation certain 1 but compromises affinity for viral receptor. R493Q reversion mutation, however, restores receptor consequently fitness BA.4/5. Among authorized clinical use, bebtelovimab retains full potency against lineage continues evolve, successively yielding are not transmissible also evasive antibodies.

Language: Английский

Citations

714
Origin, virological features, immune evasion and intervention of SARS-CoV-2 Omicron sublineages DOI Creative Commons
Shuai Xia, Lijue Wang, Yun Zhu

et al.

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

Published: July 19, 2022

Recently, a large number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continuously emerged and posed major threat to global public health. Among them, particularly, Omicron variant (B.1.1.529), first identified in November 2021, carried numerous mutations its spike protein (S), then quickly spread around the world. Currently, has expanded into more than one hundred sublineages, such as BA.1, BA.2, BA.2.12.1, BA.4 BA.5, which have already become globally dominant variants. Different from other concern (VOCs) SARS-CoV-2, sublineages exhibit increased transmissibility immune escape neutralizing antibodies generated through previous infection or vaccination, caused re-infections breakthrough infections. In this prospective, we focused on origin, virological features, evasion intervention will benefit development next-generation vaccines therapeutics, including pan-sarbecovirus universal anti-CoV combat currently circulating future emerging well SARS-CoV-2

Language: Английский

Citations

137
Fast and sensitive CRISPR detection by minimized interference of target amplification DOI
Xiaohan Tong, Kun Zhang,

Yang Han

et al.

Nature Chemical Biology, Journal Year: 2024, Volume and Issue: 20(7), P. 885 - 893

Published: Feb. 8, 2024

Language: Английский

Citations

28
Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents infection of Omicron lineages DOI Creative Commons
Harold Marcotte, Yunlong Cao, Fanglei Zuo

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(3)

Published: Jan. 9, 2024

The emergence of Omicron lineages and descendent subvariants continues to present a severe threat the effectiveness vaccines therapeutic antibodies. We have previously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by mRNA is associated with surge in breakthrough infections. Here, we further show intramuscular and/or inactivated cannot sufficiently boost secretory IgA uninfected individuals, particularly against variant. thus engineered characterized recombinant monomeric, dimeric, IgA1 antibodies derived from four neutralizing IgG monoclonal (mAbs 01A05, rmAb23, DXP-604, XG014) targeting receptor-binding domain spike protein. Compared their parental antibodies, dimeric showed higher activity different variants concern (VOCs), part due increased avidity. Importantly, or form DXP-604 antibody significantly outperformed its antibody, neutralized BA.1, BA.2, BA.4/5 25- 75-fold increase potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, single intranasal dose conferred prophylactic protection BA.5. Thus, delivered nasal administration may potentially be exploited for treatment prevention infection, thereby providing alternative tool combating immune evasion current circulating and, potentially, future VOCs.

Language: Английский

Citations

21
Tuberculosis vaccines and therapeutic drug: challenges and future directions DOI Creative Commons

Yajing An,

Ruizi Ni,

Zhuang Li

et al.

Molecular Biomedicine, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 22, 2025

Abstract Tuberculosis (TB) remains a prominent global health challenge, with the World Health Organization documenting over 1 million annual fatalities. Despite deployment of Bacille Calmette-Guérin (BCG) vaccine and available therapeutic agents, escalation drug-resistant Mycobacterium tuberculosis strains underscores pressing need for more efficacious vaccines treatments. This review meticulously maps out contemporary landscape TB development, focus on antigen identification, clinical trial progress, obstacles future trajectories in research. We spotlight innovative approaches, such as multi-antigen mRNA technology platforms. Furthermore, delves into current therapeutics, particularly multidrug-resistant (MDR-TB), exploring promising agents like bedaquiline (BDQ) delamanid (DLM), well potential host-directed therapies. The hurdles development encompass overcoming diversity, enhancing effectiveness across diverse populations, advancing novel Future initiatives emphasize combinatorial strategies, anti-TB compounds targeting pathways, personalized medicine treatment prevention. notable advances, persistent challenges diagnostic failures protracted regimens continue to impede progress. work aims steer research endeavors toward groundbreaking providing crucial insights prevention strategies.

Language: Английский

Citations

3
The lethal K18-hACE2 knock-in mouse model mimicking the severe pneumonia of COVID-19 is practicable for antiviral development DOI Creative Commons

Zhen Zhang,

Li Zhou, Qianyun Liu

et al.

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 13(1)

Published: May 16, 2024

Animal models of COVID-19 facilitate the development vaccines and antivirals against SARS-CoV-2. The efficacy or may differ in different animal with varied degrees disease. Here, we introduce a mouse model expressing human angiotensin-converting enzyme 2 (ACE2). In this model,

Language: Английский

Citations

8
Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, and BA.5 DOI Open Access
Qian Wang, Yicheng Guo, Sho Iketani

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: May 26, 2022

Abstract SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged dramatically to become dominant in the United States South Africa, respectively 1,2 . These novel carrying additional mutations their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby compromising efficacy of COVID-19 vaccines therapeutic monoclonals. We now report findings from a systematic antigenic analysis these surging subvariants. is only modestly (1.8-fold) more resistant sera vaccinated boosted individuals than BA.2. However, substantially (4.2-fold) thus likely lead vaccine breakthrough infections. Mutation at residue L452 found both facilitates escape some antibodies directed so-called class 2 3 regions receptor-binding domain The F486V mutation certain 1 but compromises affinity for viral receptor. R493Q reversion mutation, however, restores receptor consequently fitness BA.4/5. Among authorized clinical use, bebtelovimab retains full potency against lineage continues evolve, successively yielding are not transmissible also evasive antibodies.

Language: Английский

Citations

32
Comparative Review of the State of the Art in Research on the Porcine Epidemic Diarrhea Virus and SARS-CoV-2, Scope of Knowledge between Coronaviruses DOI Creative Commons
Nora Hilda Rosas-Murrieta,

Alan Rodríguez-Enríquez,

Irma Herrera‐Camacho

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 238 - 238

Published: Feb. 2, 2024

This review presents comparative information corresponding to the progress in knowledge of some aspects infection by porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronaviruses. PEDV is an alphacoronavirus great economic importance due million-dollar losses it generates pig industry. has many similarities SARS-CoV-2 betacoronavirus that causes COVID-19 disease. possible scenarios for based on collected literature tools or strategies currently developed would be useful research. The speed study generation control pandemic was derived from infections caused other human coronaviruses such as (SARS) middle east (MERS). Therefore, obtained several coronaviruses, current future behavior could inferred and, with large amount COVID-19, improved probably new emerging re-emerging

Language: Английский

Citations

7
A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug DOI Creative Commons
Qianyun Liu, Yuchi Lu,

Chenguang Cai

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(6)

Published: June 28, 2024

Abstract SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its domain. Blocking this interaction has been proven be an effective approach inhibit virus infection. Here we report discovery of a neutralizing nanobody named VHH60, which was directly produced from engineering library based on commercialized within very short period. VHH60 competes with ACE2 bind domain protein at S 351 , 470-471 and 493-494 as determined structural analysis, affinity 2.56 nM. It inhibits infections both ancestral strain pseudotyped viruses harboring wildtype, key mutations or variants nanomolar level. Furthermore, suppressed propagation 50-fold better protected mice death for twice long control group after nasal in vivo. Therefore, not only powerful promising profile disease but also provides evidence highly rapid generating therapeutic nanobodies.

Language: Английский

Citations

6
ACE2-using merbecoviruses: Further evidence of convergent evolution of ACE2 recognition by NeoCoV and other MERS-CoV related viruses DOI Creative Commons
Qing Xiong,

Chengbao Ma,

Chen Liu

et al.

Cell Insight, Journal Year: 2024, Volume and Issue: 3(1), P. 100145 - 100145

Published: Jan. 30, 2024

Angiotensin-converting enzyme 2 (ACE2) was recognized as an entry receptor shared by coronaviruses from

Language: Английский

Citations

5