Convergent Evolution in SARS-CoV-2 Spike Creates a Variant Soup from Which New COVID-19 Waves Emerge

Focosi, Daniele; Quiroga, Rodrigo; McConnell, Scott A.; Johnson, Marc C.; Casadevall, Arturo

doi:10.3390/ijms24032264

Cited by 88 publications

(86 citation statements)

References 63 publications

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“…In addition, mutations at site 346 may be able to reduce the effectiveness of neutralising antibodies [ 62 ]. The WT site interacts with ACE2 N450 via two hydrogen bonds and any substitution would result in a shorter and non-cationic sidechain, dissolving the interactions except for R346K at the BA.1.1 sub-variant [ 63 ]. Most of the Omicron sub-variants show a concerning evolution towards Ser (group 2, group 3, group 6, BQ.1, BR.2, and BM.2) and Thr (BA.2.75.1, BA.2.75.6, BF.7, BM.4.1.1, BQ.1.1, BA.2.75.2, and BL.1) [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Deep Structural Analysis of Myriads of Omicron Sub-Variants Revealed Hotspot for Vaccine Escape Immunity

et al. 2023

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The emergence of the Omicron variant has reinforced the importance of continued SARS-CoV-2 evolution and its possible impact on vaccine effectiveness. Specifically, mutations in the receptor-binding domain (RBD) are critical to comprehend the flexibility and dynamicity of the viral interaction with the human agniotensin-converting enzyme 2 (hACE2) receptor. To this end, we have applied a string of deep structural and genetic analysis tools to map the substitution patterns in the S protein of major Omicron sub-variants (n = 51) with a primary focus on the RBD mutations. This head-to-head comparison of Omicron sub-variants revealed multiple simultaneous mutations that are attributed to antibody escape, and increased affinity and binding to hACE2. Our deep mapping of the substitution matrix indicated a high level of diversity at the N-terminal and RBD domains compared with other regions of the S protein, highlighting the importance of these two domains in a matched vaccination approach. Structural mapping identified highly variable mutations in the up confirmation of the S protein and at sites that critically define the function of the S protein in the virus pathobiology. These substitutional trends offer support in tracking mutations along the evolutionary trajectories of SAR-CoV-2. Collectively, the findings highlight critical areas of mutations across the major Omicron sub-variants and propose several hotspots in the S proteins of SARS-CoV-2 sub-variants to train the future design and development of COVID-19 vaccines.

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Section: Discussionmentioning

confidence: 99%

Deep Structural Analysis of Myriads of Omicron Sub-Variants Revealed Hotspot for Vaccine Escape Immunity

et al. 2023

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“…Meanwhile, the additional mutation F490S in XBB/XBB.1/XBB.1.5 can abolish the cation‐ π interaction and result in the loss of antibody neutralization 3 . In addition to the RBD, the Y144del substitution in the NTD of the XBB lineage has been associated with robust immune evasion from NTD‐targeting neutralization antibodies 36–39 …”

Section: Immune Evasion Of Bq1 and Xbb Lineagesmentioning

confidence: 99%

“…3 In addition to the RBD, the Y144del substitution in the NTD of the XBB lineage has been associated with robust immune evasion from NTD-targeting neutralization antibodies. [36][37][38][39]…”

Section: Spike Mutations and Immune Evasionmentioning

confidence: 99%

The rapid rise of SARS‐CoV‐2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants

Hong

et al. 2023

MedComm

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

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“…During that time, SARS-CoV-2 underwent significant mutations [ 1 ], resulting in Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), Gamma (P.1), and Omicron variants of concern (VOC). The most recent of these is the Omicron subvariant XBB.1.5, which is expected to be the aetiology of the majority of USA COVID-19 infections by early 2023 [ 2 , 3 , 4 , 5 ]. Unlike the original Wuhan strain, Omicron variants induce clinical symptoms associated with the upper respiratory tract and larynx, where the airway temperature is significantly lower [ 6 ], the viral replication rate is considerably higher [ 7 ], and the hosts’ immune response is reduced.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 and Diarylamidines: The Parasitic Connection

Hulme

2023

IJMS

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As emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (Omicron) continue to outpace and negate combinatorial vaccines and monoclonal antibody therapies targeting the spike protein (S) receptor binding domain (RBD), the appetite for developing similar COVID-19 treatments has significantly diminished, with the attention of the scientific community switching to long COVID treatments. However, treatments that reduce the risk of “post-COVID-19 syndrome” and associated sequelae remain in their infancy, particularly as no established criteria for diagnosis currently exist. Thus, alternative therapies that reduce infection and prevent the broad range of symptoms associated with ‘post-COVID-19 syndrome’ require investigation. This review begins with an overview of the parasitic–diarylamidine connection, followed by the renin-angiotensin system (RAS) and associated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSSR2) involved in SARS-CoV-2 infection. Subsequently, the ability of diarylamidines to inhibit S-protein binding and various membrane serine proteases associated with SARS-CoV-2 and parasitic infections are discussed. Finally, the roles of diarylamidines (primarily DIZE) in vaccine efficacy, epigenetics, and the potential amelioration of long COVID sequelae are highlighted.

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Convergent Evolution in SARS-CoV-2 Spike Creates a Variant Soup from Which New COVID-19 Waves Emerge

Cited by 88 publications

References 63 publications

Deep Structural Analysis of Myriads of Omicron Sub-Variants Revealed Hotspot for Vaccine Escape Immunity

Deep Structural Analysis of Myriads of Omicron Sub-Variants Revealed Hotspot for Vaccine Escape Immunity

The rapid rise of SARS‐CoV‐2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants

COVID-19 and Diarylamidines: The Parasitic Connection

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