Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

Wang, Qian; Iketani, Sho; Li, Zhiteng; Liu, Liyuan; Guo, Yicheng; Huang, Yiming; Bowen, Anthony; Liu, Mengmeng; Wang, Maple; Yu, Jian; Valdez, Riccardo; Lauring, Adam S.; Sheng, Zizhang; Wang, Harris H.; Gordon, Aubree; Ho, David D.

doi:10.1101/2022.11.23.517532

Cited by 37 publications

(41 citation statements)

References 45 publications

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“…Based on our experimental results as well as recent reports, it is convincing that BQ.1.1 is one of the variants exhibiting profound resistance to the antiviral humoral immunity induced by breakthrough infections of BA.2 and BA.5 as well as therapeutic monoclonal antibodies 6,21,29 . Additionally, our experiments in vitro showed that the BQ.1.1 S exhibits higher affinity to human ACE2 and greater fusogenicity than BA.5, and these abilities are conferred by two substitutions, R346T and N460K.…”

Section: Discussionsupporting

confidence: 82%

Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

Ito

Suzuki

Uriu

et al. 2022

Preprint

115

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In late 2022, although the SARS-CoV-2 Omicron subvariants have highly diversified, some lineages have convergently acquired amino acid substitutions at five critical residues in the spike protein. Here, we illuminated the evolutionary rules underlying the convergent evolution of Omicron subvariants and the properties of one of the latest lineages of concern, BQ.1.1. Our phylogenetic and epidemic dynamics analyses suggest that Omicron subvariants independently increased their viral fitness by acquiring the convergent substitutions. Particularly, BQ.1.1, which harbors all five convergent substitutions, shows the highest fitness among the viruses investigated. Neutralization assays show that BQ.1.1 is more resistant to breakthrough BA.2/5 infection sera than BA.5. The BQ.1.1 spike exhibits enhanced binding affinity to human ACE2 receptor and greater fusogenicity than the BA.5 spike. However, the pathogenicity of BQ.1.1 in hamsters is comparable to or even lower than that of BA.5. Our multiscale investigations provide insights into the evolutionary trajectory of Omicron subvariants.

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Section: Discussionsupporting

confidence: 82%

Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

Ito

Suzuki

Uriu

et al. 2022

Preprint

115

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“…The type of viral assay (live or pseudovirus), time interval to blood sample, GMT 50 , minimum and maximum neutralizing 50% dilutional titer for WA-1 (pre-Alpha wild-type) and Omicron sublineages BQ.1.1, BA.4/5, BA.4.6, BA.2.75, XBB.1 and BF.7 and number out of total that neutralized Omicron were abstracted from study text, graphs and tables. Two studies (Wang 14 and Qu 8 ) reported BQ.1 and those were separate cohorts in addition to BQ.1.1. Prism v. 9.4 (GraphPad Software, San Diego, CA, USA) was used for data analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Kurhade et al in the USA also compared GMT50after the 4 th monovalent vaccine dose or 3 mRNA doses with the 4 th the bivalent dose without COVID-19 and also after bivalent boost with recent COVID-19 13 . Wang et al in the USA compared GMT50 after three vaccine doses, the 4 th monovalent vaccine dose or 3 mRNA doses with the 4 th the bivalent dose without COVID-19, and also after 2-3 vaccine doses and recent BA.2 breakthrough infection or 3-4 mRNA vaccine doses and recent BA.4/5 breakthrough infection 14 . These diverse cohorts were assembled into 3 groups, 1) plasma after both 2-4 vaccine doses and COVID-19 (VaxCCP); 2) plasma from subjects after administration of 3-4 vaccine doses (i.e.…”

Section: Introductionmentioning

confidence: 99%

Plasma after both SARS-CoV-2 boosted vaccination and COVID-19 potently neutralizes BQ.1.1 and XBB.1

Sullivan

Franchini

Senefeld

et al. 2022

Preprint

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BackgroundThe SARS-CoV-2 Omicron variants, dominating in the late 2022 COVID-19 waves, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized so far, and the BQ.1.* sublineages, dominant in the western countries, are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individuals both with at least 3 vaccine doses and also recently recovered from Omicron COVID-19 (VaxCCP) could retain neutralizing activity against such new Omicron lineages.MethodsHere we reviewed BQ.1.1 virus neutralization data from 652 individual patient samples from 32 separate cohorts defined by boosted vaccinations with or without recent Omicron COVID-19, as well as infection without vaccination.FindingsMore than 97% of the plasma samples from individuals in the recently (within 6 months) boosted VaxCCP study cohorts neutralized BQ.1.1, XBB and BF.7 with 100% neutralization of WA-1, BA.4/5, BA.4.6 and BA.2.75. The geometric mean of the geometric mean 50% neutralizing titers (GMT(GMT50) were 201, 52 and 204 for BQ.1.1, XBB and BF.7, respectively. Compared to VaxCCP, plasma sampled from COVID-19 naïve subjects who also recently within 6 months received at least a third vaccine dose had about half of the GMT(GMT50) for all viral variants with percent neutralizations of 82%, 60% and 94% for BQ.1.1, XBB and BF.7, respectively.InterpretationBoosted VaxCCP characterized by either recent vaccine dose or infection event within 6 months represents a robust, variant-resilient, passive immunotherapy against the new Omicron BQ.1.1, XBB and BF.7 variants.FundingDepartment of Defense in collaboration with the Defense Health Agency, National Institute of Allergy and Infectious Diseases, National Institutes of Health.Research in ContextEvidence before this studyPassive antibody therapy is necessary for both prophylaxis and therapy of immunocompromised COVID-19 patients. The currently dominant SARS-CoV-2 Omicron BQ.1.1 variant is now resistantin vitroto all clinically authorized monoclonal antibodies making COVID-19 convalescent plasma the only remaining option for passive immunotherapy in the immunocompromised. There is scattered data about the efficacy of convalescent plasma at neutralizing BQ.1.1. The few prepublished manuscripts individually have limited numbers (less than 100) in subject cohorts, making systematic reviews necessary to draw robust conclusions. We searched PubMed, medRxiv and bioRxiv for manuscripts reporting virus neutralizations for BQ.1.1 using English language as a restriction. Articles lacking plasma BQ.1.1 virus neutralizations were excluded.Added value of this studyPlasma collected from donors both recently (within 6 months) vaccine boosted and convalescent from COVID-19 (VaxCCP) neutralizes BQ.1.1, XBB and BF.7 in more than 95% of cases, and with high neutralizing titers.Implications of all the available evidenceBoosted VaxCCP remains active against BQ.1.1 and other recent Omicron variants dominating the 2022-2023 Winter wave and represents a robust COVID-19 passive immunotherapy for immunocompromised patients.

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“…The Delta variant (B.1.617.2) 3,12,13 , initially identified in India, and the Omicron variant (BA.4 and BA.5) have spread worldwide. Recently, David Ho and his team reported alarming antibody evasive SARS-CoV-2 subvariants, BQ and XBB 14 . These new variants may pose a substantial challenge to controlling the spread of this virus.…”

Section: Introductionmentioning

confidence: 99%

“…Some of these mutations reduce antibodies' efficacy, hence the currently available vaccines 40,41 . Recently, BQ.1, BQ.1.1, XBB, and XBB.1 variants of SARS-CoV-2 with multiple mutations on the RBD have been reported, which markedly reduce serum neutralization 14 . Therefore, the RBD may not be an ideal target for developing novel pancoronavirus inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Discovery of highly potent small molecule pan-coronavirus fusion inhibitors

Curreli

Chau

Tran

et al. 2023

Preprint

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The unprecedented pandemic of COVID-19, caused by a novel coronavirus, SARS-CoV-2, has led to massive human suffering, death, and economic devastation worldwide. The virus is mutating fast to more transmissible and infectious variants. The Delta variant (B.1.617.2), initially identified in India, and the omicron variant (BA.4 and BA.5) have spread worldwide. In addition, recently alarming antibody evasive SARS-CoV-2 subvariants, BQ and XBB, have been reported. These new variants may pose a substantial challenge to controlling the spread of this virus. Therefore, the continued development of novel drugs having pan-coronavirus inhibition to treat and prevent infection of COVID-19 is urgently needed. These drugs will be critically important in dealing with new pandemics that will emerge in the future. We report the discovery of several highly potent small molecule pan-coronavirus inhibitors. One of which, NBCoV63, showed low nM potency against SARS-CoV-2 (IC50: 55 nM), SARS-CoV (IC50: 59 nM), and MERS-CoV (IC50: 75 nM) in pseudovirus-based assays with excellent selectivity indices (SI: as high as > 900) demonstrating its pan-coronavirus inhibition. NBCoV63 showed equally effective antiviral potency against SARS-CoV-2 mutant (D614G) and several variants of concerns (VOCs) such as B.1.617.2 (Delta), B.1.1.529/BA.1 and BA.4/BA.5 (Omicron) and K417T/E484K/N501Y (Gamma). NBCoV63 also showed similar efficacy profiles to Remdesivir against authentic SARS-CoV-2 (Hong Kong strain) and two of its variants (Delta and Omicron) by plaque reduction in Calu3 cells. Additionally, we show that NBCoV63 inhibits virus-mediated cell-to-cell fusion in a dose-dependent manner. Furthermore, the Absorption, distribution, metabolism, and excretion (ADME) data of NBCoV63 demonstrated drug-like properties.

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Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

Cited by 37 publications

References 45 publications

Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

Plasma after both SARS-CoV-2 boosted vaccination and COVID-19 potently neutralizes BQ.1.1 and XBB.1

Discovery of highly potent small molecule pan-coronavirus fusion inhibitors

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