The Spike of Concern—The Novel Variants of SARS-CoV-2

Winger, Anna; Caspari, Thomas

doi:10.3390/v13061002

Cited by 97 publications

(114 citation statements)

References 73 publications

(106 reference statements)

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“…The L452R mutation is within the S RBD, and thus may be relevant to transmissibility or immune escape [ 34 ]. The D614G mutation is the hallmark of all variants, as it promotes viral spread by increasing the number of open S protomers in the homo-trimeric receptor complex [ 35 ]. The L452R mutation increases protein stability, viral infectivity, and potentially promotes viral replication [ 36 ].…”

Section: Consmentioning

confidence: 99%

Controversy surrounding the Sputnik V vaccine

Cazzola

Rogliani

Mazzeo

et al. 2021

Respiratory Medicine

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The Sputnik V COVID-19 vaccine is a member of the so-called vector vaccines and uses two different vectors (Ad26 priming and Ad5 boost) to reduce the risk of a reduction in the effectiveness of the vaccination. Real life data indicate an efficacy of the vaccine above 97%. Low cost and no need for ultra-cold storage temperature temperatures are other pluses of the Sputnik V vaccine. However, there are also several important shortcomings that must be considered such as the possible reduction of its immunogenicity in the presence of very high Ad5 neutralizing antibody titres and the decrease with age of the antibody titres neutralizing the virus. Furthermore, there is emerging documentation that Sputnik V has a reduced neutralizing capacity against the Beta variant and all variants with the spike protein carrying the E484K substitution. Nevertheless, due to its characteristics, Sputnik V could be another useful means of satisfying the need for mass vaccination. However, it is imperative to document the efficacy and safety of the Sputnik V vaccine in individuals with high pre-existing anti-Ad26 and Ad5-neutralizing antibody titres and in those under the age of 18 or older than 60 years and be certain that Sputnik V does not cause the rare development of immune thrombotic thrombocytopenia. It is hoped that the now widespread use of this vaccine will generate a large pragmatic real-world study with data accessible to anyone interested in verifying them.

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Section: Consmentioning

confidence: 99%

Controversy surrounding the Sputnik V vaccine

Cazzola

Rogliani

Mazzeo

et al. 2021

Respiratory Medicine

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“…The threonine substitution at site 417 avoids the salt bridge formation with D30 in hACE2. Consequently, there is expected diminution in the binding affinity for the mutated structures (Winger and Caspari, 2021). As previously elucidated, the binding free energy between RBD and ACE2 reflects the infectivity (Qu et al, 2005).…”

Section: Discussionmentioning

confidence: 88%

“…In this work, the analysis of coevolution with the Bayesian Graphical Model showed that 28 pairs of sites (including the couple 484 -501) can be statistically related with a posterior probability ≥ 0.8, indicating that these sites are probably not conditionally independent. The co-occurrence of E484K and N501Y is an interesting fact, since N501Y emerged independently in P.1 and B.1.351 lineages (Winger and Caspari, 2021), as well E484K (Ferrareze et al, 2021).…”

Section: Discussionmentioning

confidence: 98%

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Molecular evolution and structural analyses of the spike glycoprotein from Brazilian SARS-CoV-2 genomes: the impact of the fixation of selected mutations

Ferrareze

Zimerman

Franceschi

et al. 2021

Preprint

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The COVID-19 pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached by July 2021 almost 200 million cases and more than 4 million deaths worldwide since its beginning in late 2019, leading to enhanced concern in the scientific community and the general population. One of the most important pieces of this host-pathogen interaction is the spike protein, which binds to the human Angiotensin-converting enzyme 2 (hACE2) cell receptor, mediates the membrane fusion and is the major target of neutralizing antibodies against SARS-CoV-2. The multiple amino acid substitutions observed in this region, specially in the Receptor Binding Domain (RBD), mainly after almost one year of its emergence (late 2020), have enhanced the hACE2 binding affinity and led to several modifications in the mechanisms of SARS-CoV-2 pathogenesis, improving the viral fitness and/or promoting immune evasion, with potential impact in the vaccine development. In this way, the present work aimed to evaluate the effect of positively selected mutations fixed in the Brazilian SARS-CoV-2 lineages and to check for mutational evidence of coevolution. Additionally, we evaluated the impact of selected mutations identified in some of the VOC and VOI lineages (C.37, B.1.1.7, P.1, and P.2) of Brazilian samples on the structural stability of the spike protein, as well as their possible association with more aggressive infection profiles by estimating the binding affinity in the RBD-hACE2 complex. We identified 48 sites under selective pressure in Brazilian spike sequences, 17 of them with the strongest evidence by the HyPhy tests, including VOC related mutation sites 138, 142, 222, 262, 484, 681, and 845, among others. The coevolutionary analysis identified a number of 28 coevolving sites that were found not to be conditionally independent, such as the couple E484K - N501Y from P.1 and B.1.351 lineages. Finally, the molecular dynamics and free energy estimates showed the structural stabilizing effect and the higher impact of E484K for the improvement of the binding affinity between the spike RBD and the hACE2 in P.1 and P.2 lineages, as well as the stabilizing and destabilizing effects for the positively selected sites.

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“…B.1.617, which is characterized by the mutations L452R and P681R, divides into 3 sublineages. B.1.617.1 and B.1.617.3 show the mutation E484Q, which apparently has similar functional consequences as E484K [ 6 ].…”

mentioning

confidence: 99%

Rapid Base-Specific Calling of SARS-CoV-2 Variants of Concern Using Combined RT-PCR Melting Curve Screening and SIRPH Technology

Tierling

Kattler

Vogelgesang

et al. 2021

Open Forum Infectious Diseases

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The emergence of novel variants of concern of SARS-CoV-2 demands a fast and reliable detection of such variants in local populations. Here we present a cost-efficient and fast workflow combining a pre-screening of SARS-CoV-2 positive samples using RT-PCR melting curve analysis with multiplexed IP-RP-HPLC-based single nucleotide primer extensions (SIRPH). The entire workflow from positive SARS-CoV-2 testing to base-specific identification of variants requires about 24 h. We applied the sensitive method to monitor the local VOC outbreaks in SARS-CoV-2 positive samples collected in a confined region of Germany.

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The Spike of Concern—The Novel Variants of SARS-CoV-2

Cited by 97 publications

References 73 publications

Controversy surrounding the Sputnik V vaccine

Controversy surrounding the Sputnik V vaccine

Molecular evolution and structural analyses of the spike glycoprotein from Brazilian SARS-CoV-2 genomes: the impact of the fixation of selected mutations

Rapid Base-Specific Calling of SARS-CoV-2 Variants of Concern Using Combined RT-PCR Melting Curve Screening and SIRPH Technology

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