Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion

Li, Pei; Liu, Yajie; Faraone, Julia; Hsu, Cheng Chih; Chamblee, Michelle; Zheng, Yi-Min; Carlin, Claire; Bednash, Joseph S.; Horowitz, Jeffrey C.; Mallampalli, Rama K.; Saif, Linda J.; Oltz, Eugene M.; Jones, Daniel; Li, Jianrong; Gumina, Richard J.; Liu, Shan-Lu

doi:10.1101/2024.03.11.583978

Cited by 2 publications

(1 citation statement)

References 39 publications

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“…We have predicted that surface AAs in trimeric spike changed in JN.1 variant (16). However, more mutations were reported in BA.2.87.1 that was activated in South Africa with different virological characteristics as compared to JN.1 and XBB.1.5 subvariants (27). Controversy on research data must be there as some ma a scientists adopted a fraud research community worldwide and somehow managed to nd funding from Government agencies.…”

Section: Resultsmentioning

confidence: 99%

Rapid worldwide spread of 17MPLF spike insertion mutants (JN.1-JN.1.25, KP.1, KP.2, KQ.1, KR.1, XDD, XDP, XDK, XDQ subvariants) of omicron coronaviruses and spike gene 5’-end sequencing problem

Chakraborty

2024

Preprint

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We postulated a higher omicron JN.1/BA.2.86.1.1 coronavirus transmission due to unique 17MPLF spike insertion compensating 24LPP, 69HV, 145Y, 211N and 483V deletions [Journal of Future Medicine and Healthcare Innovation, 2(3):1–20, 2024]. After six months of our publication in Research Square preprint, I am updating our analysis of omicron spike insertion mutants. Database analysis suggested that JN.1-JN.1.25 subvariants had such insertion and such mutants were predominantly spreading worldwide. But we found some new coronavirus variants spread in the database like KP.1, KP.2, KP.1.1, KQ.1, XDD, XDK, XDP, XDQ, XDQ.1 and more which was contradictory to our hypothesis. Similarly, previously compared HV.1, EG.5.1.1, XBB.1.1-XBB.1.103, FL.1.5.1 like variants with no 17MPLF insertion but with termination codon mutation in the ORF8 gene, was diminishing comparatively in 2024. Surprisingly, the newly spreading subvariants also contained 17MPLF insertion in the spike. Originally, KP.1 was BA.2.86.1.1.11.1 while XDQ variant was a composite of BA.2.86.1 and FL1.5.1.1 suggesting JN.1, KP.1, XDK and XDQ subvariants were very similar. As the other genetic variations were found minimal, our hypothesis was fundamentally proved. On the other hand, critical search indicated omission of ORF8 protein in some 17MPLF insertion mutants likely diminishing viral load and disease severity but frequently found ORF7a deletions were not found. We also detected unique 32S deletion in the spike of few 17MPLF insertion mutants increasing to nine AAs spike deletion in JN.1 lineages. BLASTP search using oligopeptides at the new mutations (F59L, H146Q, R346T) and deletion (32S) boundaries demonstrated the penetration of insertion mutants in the USA, UK, Russia and Japan. Contrary to our hypothesis, Opentrons P (AN: PP889628, PP916105, PP938531, PP938533, PQ009953), Sadri N (AN: PP887470, PP88747474, PP887480, PP887481), Dragon J et al. (PP938086, PP938087), and Reev V et al (AN: PP871683, PP934270, PQ012208) reported JN.1 lineages without 17MPLF spike insertion.

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Section: Resultsmentioning

confidence: 99%

Rapid worldwide spread of 17MPLF spike insertion mutants (JN.1-JN.1.25, KP.1, KP.2, KQ.1, KR.1, XDD, XDP, XDK, XDQ subvariants) of omicron coronaviruses and spike gene 5’-end sequencing problem

Chakraborty

2024

Preprint

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Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1

Yang,

Yu,

Jian

et al. 2024

Emerging Microbes & Infections

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The recent emergence of a SARS-CoV-2 saltation variant, BA.2.87.1, which features 65 spike mutations relative to BA.2, has attracted worldwide attention. In this study, we elucidate the antigenic characteristics and immune evasion capability of BA.2.87.1. Our findings reveal that BA.2.87.1 is more susceptible to XBB-induced humoral immunity compared to JN.1. Notably, BA.2.87.1 lacks critical escaping mutations in the receptor binding domain (RBD) thus allowing various classes of neutralizing antibodies (NAbs) that were escaped by XBB or BA.2.86 subvariants to neutralize BA.2.87.1, although the deletions in the N-terminal domain (NTD), specifically 15-23del and 136-146del, compensate for the resistance to humoral immunity. Interestingly, several neutralizing antibody drugs have been found to restore their efficacy against BA.2.87.1, including SA58, REGN-10933 and COV2-2196. Hence, our results suggest that BA.2.87.1 may not become widespread until it acquires multiple RBD mutations to achieve sufficient immune evasion comparable to that of JN.1.

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Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion

Cited by 2 publications

References 39 publications

Rapid worldwide spread of 17MPLF spike insertion mutants (JN.1-JN.1.25, KP.1, KP.2, KQ.1, KR.1, XDD, XDP, XDK, XDQ subvariants) of omicron coronaviruses and spike gene 5’-end sequencing problem

Rapid worldwide spread of 17MPLF spike insertion mutants (JN.1-JN.1.25, KP.1, KP.2, KQ.1, KR.1, XDD, XDP, XDK, XDQ subvariants) of omicron coronaviruses and spike gene 5’-end sequencing problem

Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1

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