In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir DOI Creative Commons
Maki Kiso, Yuri Furusawa, Ryuta Uraki

et al.

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

Published: July 4, 2023

Nirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is clinically useful against infection with including its omicron variants. Since most subvariants have reduced sensitivity to many monoclonal antibody therapies, potential resistance nirmatrelvir major public health concern. Several amino acid substitutions been identified as being responsible for susceptibility nirmatrelvir. Among them, we selected L50F/E166V and L50F/E166A/L167F in the 3CLpro because these combinations of are unlikely affect virus fitness. We prepared characterized delta variants possessing Nsp5-L50F/E166V Nsp5-L50F/E166A/L167F. Both mutant viruses showed decreased their growth VeroE6/TMPRSS2 cells was delayed. attenuated phenotypes male hamster model, maintained airborne transmissibility, were outcompeted by wild-type co-infection experiments absence nirmatrelvir, but less so presence drug. These results suggest Nsp5-L50F/E166A/L167F do not become dominant nature. However, it important closely monitor emergence nirmatrelvir-resistant resistant additional compensatory mutations could emerge, outcompete virus, dominant.

Language: Английский

Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB DOI Open Access
Ryuta Uraki,

Mutsumi Ito,

Yuri Furusawa

et al.

The Lancet Infectious Diseases, Journal Year: 2022, Volume and Issue: 23(1), P. 30 - 32

Published: Dec. 7, 2022

Language: Английский

Citations

173
Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants DOI Creative Commons
Panke Qu, Julia N. Faraone, John P. Evans

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(5), P. 112443 - 112443

Published: April 18, 2023

Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies stimulated by three doses mRNA vaccine or BA.4/5 wave infection, but neutralization is rescued a BA.5-containing bivalent booster. CH.1.1 show strong immune monoclonal antibody S309. Additionally, spike proteins exhibit increased fusogenicity enhanced processing compared with BA.2. Homology modeling reveals key roles G252V F486P in resistance also enhancing receptor binding. Further, K444T/M L452R likely drive class II antibodies, whereas R346T G339H mutations could confer these two to S309-like antibodies. Overall, our results support need for administration continued surveillance subvariants.

Language: Английский

Citations

152
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
Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants DOI Creative Commons
Panke Qu, Kai Xu, Julia N. Faraone

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 585 - 595.e6

Published: Jan. 8, 2024

Evolution of SARS-CoV-2 requires the reassessment current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, EG.5.1 sera from 3-dose-vaccinated bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, monoclonal antibody (mAb) S309. We assessed biology spikes measuring viral infectivity membrane fusogenicity. is less immune evasive compared to other XBB variants, consistent with antigenic distances. Importantly, distinct mAb S309 was unable neutralize BA.2.86, likely due a D339H mutation based on modeling. had relatively high fusogenicity in CaLu-3 cells but low fusion 293T-ACE2 some suggesting potentially different conformational stability spike. Overall, our study underscores importance surveillance need for updated COVID-19 vaccines.

Language: Английский

Citations

105
Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials DOI Open Access
Alain Amstutz, Benjamin Speich, France Mentré

et al.

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 11(5), P. 453 - 464

Published: Feb. 22, 2023

Language: Английский

Citations

92
Antiviral and bivalent vaccine efficacy against an omicron XBB.1.5 isolate DOI Open Access
Ryuta Uraki,

Mutsumi Ito,

Maki Kiso

et al.

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(4), P. 402 - 403

Published: Feb. 9, 2023

Language: Английский

Citations

87
Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies DOI Creative Commons
Nur Zawanah Zabidi, Hern Liang Liew, Isra Ahmad Farouk

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 944 - 944

Published: April 10, 2023

The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of has given rise to multiple variants varying pathogenicity transmissibility, such as Delta Omicron variants. Individuals advanced age or underlying comorbidities, including hypertension, diabetes cardiovascular diseases, are at higher risk increased disease severity. Hence, this resulted in an urgent need for development better therapeutic preventive approaches. This review describes origin human coronaviruses, particularly well sub-variants. Risk factors that contribute severity implications co-infections also considered. In addition, various antiviral strategies against COVID-19, novel repurposed drugs targeting viral host proteins, immunotherapeutic strategies, discussed. We critically evaluate current emerging vaccines their efficacy, immune evasion new impact on diagnostic testing examined. Collectively, global research public health authorities, along all sectors society, prepare upcoming future coronavirus outbreaks.

Language: Английский

Citations

70
Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3 DOI Creative Commons
Julia N. Faraone, Panke Qu,

Negin Goodarzi

et al.

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(2)

Published: Oct. 11, 2023

Immune evasion by SARS-CoV-2 paired with immune imprinting from monovalent mRNA vaccines has resulted in attenuated neutralizing antibody responses against Omicron subvariants. In this study, we characterized two new XBB variants rising circulation - EG.5.1 and XBB.2.3, for their neutralization syncytia formation. We determined the titers sera of individuals that received a bivalent vaccine booster, BA.4/5-wave infection, or XBB.1.5-wave infection. Bivalent vaccination-induced antibodies neutralized ancestral D614G efficiently, but to much less extent, XBB.2.3 variants. fact, enhanced escape appeared be driven its key defining mutation XBB.1.5-F456L. Notably, infection BA.4/5 XBB.1.5 afforded little, if any, EG.5.1, previous especially unvaccinated individuals, average near limit detection. Additionally, investigated infectivity, fusion activity, processing variant spikes HEK293T-ACE2 CaLu-3 cells found no significant differences compared earlier Overall, our findings highlight continued subvariants and, more importantly, need reformulate include better protection.

Language: Английский

Citations

70
Identification of a conserved S2 epitope present on spike proteins from all highly pathogenic coronaviruses DOI Creative Commons

Rui P. Silva,

Yimin Huang, Annalee W. Nguyen

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: March 21, 2023

To address the ongoing SARS-CoV-2 pandemic and prepare for future coronavirus outbreaks, understanding protective potential of epitopes conserved across variants lineages is essential. We describe a highly conserved, conformational S2 domain epitope present only in prefusion core β-coronaviruses: apex residues 980–1006 flexible hinge. Antibody RAY53 binds native hinge MERS-CoV spikes on surface mammalian cells mediates antibody-dependent cellular phagocytosis cytotoxicity against spike vitro. Hinge mutations that ablate antibody binding compromise pseudovirus infectivity, but changes elsewhere affect opening dynamics, including those found Omicron BA.1, occlude may evade pre-existing serum antibodies targeting core. This work defines third class while providing insights into potency limitations targeting.

Language: Английский

Citations

66
Immune Evasion, Infectivity, and Fusogenicity of SARS-CoV-2 Omicron BA.2.86 and FLip Variants DOI
Panke Qu, Kai Xu, Julia N. Faraone

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 12, 2023

Evolution of SARS-CoV-2 requires the reassessment current vaccine measures. Here, we characterized BA.2.86 and XBB-lineage variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, EG.5.1 sera from 3-dose vaccinated bivalent healthcare workers, XBB.1.5-wave infected first responders, monoclonal antibody (mAb) S309. We assessed biology Spikes measuring viral infectivity membrane fusogenicity. is less immune evasive compared to other XBB variants, consistent with antigenic distances. Importantly, distinct mAb S309 was unable neutralize BA.2.86, likely due a D339H mutation based on modeling. had relatively high fusogenicity in CaLu-3 cells but low fusion 293T-ACE2 some suggesting potentially differences conformational stability Spike. Overall, our study underscores importance surveillance need for updated COVID-19 vaccines.

Language: Английский

Citations

46