Global landscape of SARS-CoV-2 mutations and conserved regions

Abbasian, Mohammad Hadi; Mahmanzar, Mohammadamin; Rahimian, Karim; Mahdavi, Bahar; Tokhanbigli, Samaneh; Moradi, Bahman; Sisakht, Mahsa Mollapour; Deng, Youping

doi:10.1186/s12967-023-03996-w

Cited by 46 publications

(35 citation statements)

References 101 publications

(117 reference statements)

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“…The availability of more upgraded genome sequences opens up opportunities for us to discover new viral mutations that signi cantly contribute to the transmission of SARS-CoV-2. Hence, an advanced systematic review of SARS-CoV-2 global mutations is required to explore the relationship between genomic features and geographic locations during outbreak [15][16][17]. Here, we investigated up-to-date whole mutations among 6.5 million samples in entire the genome of SARS-CoV-2 (Fig.…”

Section: Introductionmentioning

confidence: 99%

Mutation Accumulation of SARS-CoV-2 Genome in North America, South America, and Oceania: Analysis of Over 6.5 Million Sequences Samples from Global Initiative on Sharing Avian Influenza Data

et al. 2022

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Section: Introductionmentioning

confidence: 99%

Mutation Accumulation of SARS-CoV-2 Genome in North America, South America, and Oceania: Analysis of Over 6.5 Million Sequences Samples from Global Initiative on Sharing Avian Influenza Data

et al. 2022

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“…However, given that 2NSP23 expression rescues these gene programs, it is likely that Nsp9, being an RNA-binding protein, might interact with nuclear factors and directly affect gene expression at transcriptional level in the host cells. So, 2NSP23 nanobody is ideally suited to function as potential antiviral to combat SARS-CoV-2 infection and infections by closely related viruses such as MERS and SARS-CoV considering the extremely low degree of mutagenicity of Nsp9 (Abbasian et al 2023). However, the remarkable finding that treatment of uninfected cells with 2NSP23 elicits enrichment of genes related to defense response to viruses also suggest a potentially much broader use of this nanobody in general prophylaxis to combat pathogens.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Nanobodies against SARS-CoV-2 non-structural protein Nsp9 inhibit viral replication by targeting innate immunity

Venit,

Blavier,

Maseko

et al. 2023

Preprint

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Nanobodies are emerging as critical tools for drug design. Several have been recently created to serve as inhibitors of SARS-Cov-2 entry in the host cell by targeting surface-exposed Spike protein. However, due to the high frequency of mutations that affect Spike, these nanobodies may not target it to their full potential and as a consequence, inhibition of viral entry may not be efficient. Here we have established a pipeline that instead targets highly conserved viral proteins that are made only after viral entry into the host cell when the SARS-Cov-2 RNA-based genome is translated. As proof of principle, we designed nanobodies against the SARS-CoV-2 non-structural protein Nsp9, required for viral genome replication. To find out if this strategy efficiently blocks viral replication, one of these anti-Nsp9 nanobodies, 2NSP23, previously characterized using immunoassays and NMR spectroscopy for epitope mapping, was encapsulated into lipid nanoparticles (LNP) as mRNA. We show that this nanobody, hereby referred to as LNP-mRNA-2NSP23, is internalized and translated in HEK293 cells. We next infected HEK293-ACE2 cells with multiple SARS-CoV-2 variants and subjected them to LNP-mRNA-2NSP23 treatment. Analysis of total RNA isolated from infected cells treated or untreated with LNP-mRNA-2NSP23 using qPCR and RNA deep sequencing shows that the LNP-mRNA-2NSP23 nanobody protects HEK293-ACE2 cells and suppresses replication of several SARS-CoV-2 variants. These observations indicate that following translation, the nanobody 2NSP23 inhibits viral replication by targeting Nsp9 in living cells. We speculate that LNP-mRNA-2NSP23 may be translated into an innovative technology to generate novel antiviral drugs highly efficient across coronaviruses.

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“…It is possible that most wild type strains of SARS-CoV-2 would kill infected cells more quickly. However, there are a variety of mutations found in ORF7 in circulating SARS-CoV-2 strains that could affect its function during infection 4344, 45 .…”

Section: Discussionmentioning

confidence: 99%

Live imaging of the airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread

Hope,

Becker,

Martin-Sancho

et al. 2023

Preprint

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SARS-CoV-2 initiates infection in the conducting airways, which rely on mucocilliary clearance (MCC) to minimize pathogen penetration. However, it is unclear how MCC impacts SARS-CoV-2 spread after infection is established. To understand viral spread at this site, we performed live imaging of SARS-CoV-2 infected differentiated primary human bronchial epithelium cultures for up to 9 days. Fluorescent markers for cilia and mucus allowed longitudinal monitoring of MCC, ciliary motion, and infection. The number of infected cells peaked at 4 days post-infection in characteristic foci that followed mucus movement. Inhibition of MCC using physical and genetic perturbations limited foci. Later in infection, MCC was diminished despite relatively subtle ciliary function defects. Resumption of MCC and infection spread after mucus removal suggests that mucus secretion mediates this effect. We show that MCC facilitates SARS-CoV-2 spread early in infection while later decreases in MCC inhibit spread, suggesting a complex interplay between SARS-CoV-2 and MCC.

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Global landscape of SARS-CoV-2 mutations and conserved regions

Cited by 46 publications

References 101 publications

Mutation Accumulation of SARS-CoV-2 Genome in North America, South America, and Oceania: Analysis of Over 6.5 Million Sequences Samples from Global Initiative on Sharing Avian Influenza Data

Mutation Accumulation of SARS-CoV-2 Genome in North America, South America, and Oceania: Analysis of Over 6.5 Million Sequences Samples from Global Initiative on Sharing Avian Influenza Data

Nanobodies against SARS-CoV-2 non-structural protein Nsp9 inhibit viral replication by targeting innate immunity

Live imaging of the airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread

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