Receptor binding, immune escape, and protein stability direct the natural selection of SARS-CoV-2 variants

Upadhyay, Vaibhav; Lucas, Alexandra; Panja, Sudipta; Miyauchi, Ryuki; Mallela, Krishna

doi:10.1016/j.jbc.2021.101208

Cited by 42 publications

(83 citation statements)

References 75 publications

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“…An alternative explanation for positive selection of mutations within the RBD of SARS-CoV-2 is enhancement of resistance to postvaccinated sera [ 24 ]. Studies testing monoclonal antibodies isolated from SARS-CoV-2-vaccinated individuals have demonstrated resistance conferred by nearly all RBD mutations [ 19 , 25 , 26 , 27 , 28 ] ( Figure 3 d). This is not surprising as 40% of the antibodies produced against SARS-CoV-2 target the RBD, and the vast majority of these antibodies are neutralizing antibodies [ 29 ].…”

Section: Mutations Of the S1 Subunit Containing The Receptor-binding ...mentioning

confidence: 99%

Mutations and Evolution of the SARS-CoV-2 Spike Protein

Magazine

Zhang

et al. 2022

Viruses

173

110

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The SARS-CoV-2 spike protein mediates target recognition, cellular entry, and ultimately the viral infection that leads to various levels of COVID-19 severities. Positive evolutionary selection of mutations within the spike protein has led to the genesis of new SARS-CoV-2 variants with greatly enhanced overall fitness. Given the trend of variants with increased fitness arising from spike protein alterations, it is critical that the scientific community understand the mechanisms by which these mutations alter viral functions. As of March 2022, five SARS-CoV-2 strains were labeled “variants of concern” by the World Health Organization: the Alpha, Beta, Gamma, Delta, and Omicron variants. This review summarizes the potential mechanisms by which the common mutations on the spike protein that occur within these strains enhance the overall fitness of their respective variants. In addressing these mutations within the context of the SARS-CoV-2 spike protein structure, spike/receptor binding interface, spike/antibody binding, and virus neutralization, we summarize the general paradigms that can be used to estimate the effects of future mutations along SARS-CoV-2 evolution.

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Section: Mutations Of the S1 Subunit Containing The Receptor-binding ...mentioning

confidence: 99%

Mutations and Evolution of the SARS-CoV-2 Spike Protein

Magazine

Zhang

et al. 2022

Viruses

173

110

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“…The choice of the buffer composition was dictated by the stability of the proteins. Even though these conditions are not optimal for a CD study, they allowed us to assess that the refolded protocol we devised to obtain the SARS-CoV-2 RBD from E. coli worked and that the produced RBDs were folded in those conditions, as indicated (i) by the similarity of the overall far-UV-CD shape with what previously reported for HEK, insect and E. coli RBDs [ 21 , 32 , 41 ], (ii) by the overall consistency in the distribution of the secondary structure composition of the proteins and (iii) by the agreement of the calculated melting temperatures with those reported in the literature in equivalent ionic strength conditions [ 21 ]. Notably, we can exclude an effect of the presence of TCEP on the differences observed between the CD spectra of E. coli -RBD and the ones of HEK-293- and Insect-RBDs, since the spectrum profile of the RBD from E. coli reported in Mycroft-West et al [ 32 ] was obtained in the absence of the reducing agent.…”

Section: Discussionmentioning

confidence: 99%

The Nuts and Bolts of SARS-CoV-2 Spike Receptor-Binding Domain Heterologous Expression

Maffei¹,

Montemiglio

Vitagliano³

et al. 2021

Biomolecules

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COVID-19 is a highly infectious disease caused by a newly emerged coronavirus (SARS-CoV-2) that has rapidly progressed into a pandemic. This unprecedent emergency has stressed the significance of developing effective therapeutics to fight the current and future outbreaks. The receptor-binding domain (RBD) of the SARS-CoV-2 surface Spike protein is the main target for vaccines and represents a helpful “tool” to produce neutralizing antibodies or diagnostic kits. In this work, we provide a detailed characterization of the native RBD produced in three major model systems: Escherichia coli, insect and HEK-293 cells. Circular dichroism, gel filtration chromatography and thermal denaturation experiments indicated that recombinant SARS-CoV-2 RBD proteins are stable and correctly folded. In addition, their functionality and receptor-binding ability were further evaluated through ELISA, flow cytometry assays and bio-layer interferometry.

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“…Structure predictions revealed that N500Y may play a significant role in virus binding to ACE2. The K417T and E484K may enhance viral expression and enable the virus to escape from the human immune system [ 27 ]. The Gamma variant revealed a 1.7- to 2.4-fold higher degree of transmission compared to the non-P.1 variants [ 26 ].…”

Section: Virus Variants Of Concern (Vocs) and Former Vocsmentioning

confidence: 99%

COVID-19 Genetic Variants and Their Potential Impact in Vaccine Development

Giau

Bagyinszky

2022

Microorganisms

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In the two years since the SARS-CoV-2 pandemic started, it has caused over 5 million deaths and 400 million infected cases, and the world continues to be on high alert for COVID-19. Among the variants of interest and concern of SARS-CoV-2, the current Omicron (B.1.1.529) and stealth Omicron (BA.2) raised serious concerns due to rapid rates of infection caused by numerous mutations in the spike protein, which could escape from the antibody-mediated neutralization and increase the risk of reinfections. Hence, this work aims to describe the most relevant mutations in the SARS-CoV-2 spike protein, discuss vaccine against variant of concerns, describe rare adverse events after COVID-19 vaccination, introduce the most available promising COVID-19 vaccine candidates, and provide few perspectives of the future variants.

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Receptor binding, immune escape, and protein stability direct the natural selection of SARS-CoV-2 variants

Cited by 42 publications

References 75 publications

Mutations and Evolution of the SARS-CoV-2 Spike Protein

Mutations and Evolution of the SARS-CoV-2 Spike Protein

The Nuts and Bolts of SARS-CoV-2 Spike Receptor-Binding Domain Heterologous Expression

COVID-19 Genetic Variants and Their Potential Impact in Vaccine Development

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