Global challenge with the SARS-CoV-2 omicron BA.2 (B.1.1.529.2) subvariant: Should we be concerned?

Roohani, Jalil; Keikha, Masoud

doi:10.5501/wjv.v11.i6.496

Cited by 2 publications

(2 citation statements)

References 20 publications

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“…The Delta variant (B.1.617.2) identified in October 2020 showed increased transmissibility and disease severity compared to the WT [3]. Omicron (B.1.1.529) variants, including BA.1, BA.2, BA.3, BA.4, and BA.5, were first observed in November 2021; they were more infectious than all of the previous variants and became the dominant VOC around the world [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

The Recognition Pathway of the SARS-CoV-2 Spike Receptor-Binding Domain to Human Angiotensin-Converting Enzyme 2

Peng,

Lv,

Zhang

et al. 2024

Molecules

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COVID-19 caused by SARS-CoV-2 has spread around the world. The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 is a critical component that directly interacts with host ACE2. Here, we simulate the ACE2 recognition processes of RBD of the WT, Delta, and OmicronBA.2 variants using our recently developed supervised Gaussian accelerated molecular dynamics (Su-GaMD) approach. We show that RBD recognizes ACE2 through three contact regions (regions I, II, and III), which aligns well with the anchor–locker mechanism. The higher binding free energy in State d of the RBDOmicronBA.2-ACE2 system correlates well with the increased infectivity of OmicronBA.2 in comparison with other variants. For RBDDelta, the T478K mutation affects the first step of recognition, while the L452R mutation, through its nearby Y449, affects the RBDDelta-ACE2 binding in the last step of recognition. For RBDOmicronBA.2, the E484A mutation affects the first step of recognition, the Q493R, N501Y, and Y505H mutations affect the binding free energy in the last step of recognition, mutations in the contact regions affect the recognition directly, and other mutations indirectly affect recognition through dynamic correlations with the contact regions. These results provide theoretical insights for RBD-ACE2 recognition and may facilitate drug design against SARS-CoV-2.

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Section: Introductionmentioning

confidence: 99%

The Recognition Pathway of the SARS-CoV-2 Spike Receptor-Binding Domain to Human Angiotensin-Converting Enzyme 2

Peng,

Lv,

Zhang

et al. 2024

Molecules

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“…Novel Coronavirus Omicron new subtype BQ. 1.1 is resistant to all currently known monoclonal antibody therapies ( Cao et al., 2022 ; Roohani and Keikha, 2022 ; Arora et al., 2023 ). According to the Global Initiative for Shared Influenza Data (GISAID), XBB.…”

Section: Introductionmentioning

confidence: 99%

The antiviral activity of a small molecule drug targeting the NSP1-ribosome complex against Omicron, especially in elderly patients

Shen

Ding

Luan

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionWith the emergence of SARS-CoV-2 mutant strains, especially the epidemic of Omicron, it continues to evolve to strengthen immune evasion. Omicron BQ. 1 and XBB pose a serious threat to the current COVID-19 vaccine (including bivalent mRNA vaccine for mutant strains) and COVID-19-positive survivors, and all current therapeutic monoclonal antibodies are ineffective against them. Older people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalization and death after the initial vaccine booster. However, small-molecule drugs for conserved targets remain effective and urgently needed.MethodsThe non-structural protein of SARS-CoV-2 non-structural protein 1(Nsp1) can bind to the host 40S ribosomal subunit and activate the nuclease to hydrolyze the host RNA, while the viral RNA is unaffected, thus hijacking the host system. First, the present study analyzed mutations in the Nsp1 protein and then constructed a maximum-likelihood phylogenetic tree. A virtual drug screening method based on the Nsp1 structure (Protein Data Bank ID: 7K5I) was constructed, 7495 compounds from three databases were collected for molecular docking and virtual screening, and the binding free energy was calculated by the MM/GBSA method.ResultsOur study shows that Nsp1 is relatively conserved and can be used as a comparatively fixed drug target and that therapies against Nsp1 will target all of these variants. Golvatinib, Gliquidone, and Dihydroergotamine were superior to other compounds in the crystal structure of binding conformation and free energy. All effectively interfered with Nsp1 binding to 40S protein, confirming the potential inhibitory effect of these three compounds on SARS-CoV-2.DiscussionIn particular, Golwatinib provides a candidate for treatment and prophylaxis in elderly patients with Omicjon, suggesting further evaluation of the anti-SARS-CoV-2 activity of these compounds in cell culture. Further studies are needed to determine the utility of this finding through prospective clinical trials and identify other meaningful drug combinations.

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Global challenge with the SARS-CoV-2 omicron BA.2 (B.1.1.529.2) subvariant: Should we be concerned?

Cited by 2 publications

References 20 publications

The Recognition Pathway of the SARS-CoV-2 Spike Receptor-Binding Domain to Human Angiotensin-Converting Enzyme 2

The Recognition Pathway of the SARS-CoV-2 Spike Receptor-Binding Domain to Human Angiotensin-Converting Enzyme 2

The antiviral activity of a small molecule drug targeting the NSP1-ribosome complex against Omicron, especially in elderly patients

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