Origins and Evolution of Seasonal Human Coronaviruses

Otieno, JR; Cherry, JL; Dj, Spiro; Nelson, MI; Trovao, NS

doi:10.1101/2022.06.02.494567

Cited by 2 publications

References 94 publications

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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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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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Evaluating the Virology and Evolution of Seasonal Human Coronaviruses Associated with the Common Cold in the COVID-19 Era

et al. 2023

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Approximately 15–30% of all cases of the common cold are due to human coronavirus infections. More recently, the emergence of the more severe respiratory coronaviruses, SARS-CoV and MERS-CoV, have highlighted the increased pathogenic potential of emergent coronaviruses. Lastly, the current emergence of SARS-CoV-2 has demonstrated not only the potential for significant disease caused by emerging coronaviruses, but also the capacity of novel coronaviruses to promote pandemic spread. Largely driven by the global response to the COVID-19 pandemic, significant research in coronavirus biology has led to advances in our understanding of these viruses. In this review, we evaluate the virology, emergence, and evolution of the four endemic coronaviruses associated with the common cold, their relationship to pandemic SARS-CoV-2, and discuss the potential for future emergent human coronaviruses.

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Origins and Evolution of Seasonal Human Coronaviruses

Cited by 2 publications

References 94 publications

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

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

Evaluating the Virology and Evolution of Seasonal Human Coronaviruses Associated with the Common Cold in the COVID-19 Era

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