Differential efficiencies to neutralize the novel mutants B.1.1.7 and 501Y.V2 by collected sera from convalescent COVID-19 patients and RBD nanoparticle-vaccinated rhesus macaques

Li, Rong; Ma, Xiancai; Deng, Jieyi; Chen, Qier; Liu, Weiwei; Peng, Zhilin; Qiao, Yidan; Lin, Yingtong; He, Xin; Zhang, Hui

doi:10.1038/s41423-021-00641-8

Cited by 24 publications

(24 citation statements)

References 17 publications

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“…As new strains of SARS-CoV-2 with several dominant mutations in the spike protein have been identified recently, crucial questions associated with the possible reinfection of recovered patients and the efficiencies of vaccines designed based on early epidemic strains have arisen [22]. Recent findings show that sera collected from convalescent COVID-19 patients in early 2020 vaccinated with RBD-based vaccines efficiently neutralize viral variants of D614G and B.1.1.7 but weakly neutralize those of 501Y.V2, suggesting a warning to recovered patients and developed vaccines [312]. These results show that, as mutations accumulate in the RBD, spike proteins may acquire an antigenic shift that enable SARS-CoV-2 variants with loss-of-neutralization potency in vitro against emerging variants and eventually resist the current vaccines.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis

Peng¹,

Rhind²,

Beckett³

2021

JMIR Public Health Surveill

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Background The COVID-19 pandemic, caused by a novel coronavirus termed SARS-CoV-2, has spread quickly worldwide. Convalescent plasma (CP) obtained from patients following recovery from COVID-19 infection and development of antibodies against the virus is an attractive option for either prophylactic or therapeutic treatment, since antibodies may have direct or indirect antiviral activities and immunotherapy has proven effective in principle and in many clinical reports. Objective We seek to characterize the latest advances and evidence in the use of CP for COVID-19 through a systematic review and quantitative analysis, identify knowledge gaps in this setting, and offer recommendations and directives for future research. Methods PubMed, Web of Science, and Embase were continuously searched for studies assessing the use of CP for COVID-19, including clinical studies, commentaries, reviews, guidelines or protocols, and in vitro testing of CP antibodies. The screening process and data extraction were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality appraisal of all clinical studies was conducted using a universal tool independent of study designs. A meta-analysis of case-control and randomized controlled trials (RCTs) was conducted using a random-effects model. Results Substantial literature has been published covering various aspects of CP therapy for COVID-19. Of the references included in this review, a total of 243 eligible studies including 64 clinical studies, 79 commentary articles, 46 reviews, 19 guidance and protocols, and 35 in vitro testing of CP antibodies matched the criteria. Positive results have been mostly observed so far when using CP for the treatment of COVID-19. There were remarkable heterogeneities in the CP therapy with respect to patient demographics, donor antibody titers, and time and dose of CP administration. The studies assessing the safety of CP treatment reported low incidence of adverse events. Most clinical studies, in particular case reports and case series, had poor quality. Only 1 RCT was of high quality. Randomized and nonrandomized data were found in 2 and 11 studies, respectively, and were included for meta-analysis, suggesting that CP could reduce mortality and increase viral clearance. Despite promising pilot studies, the benefits of CP treatment can only be clearly established through carefully designed RCTs. Conclusions There is developing support for CP therapy, particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. These studies provide important lessons that should inform the planning of well-designed RCTs to generate more robust knowledge for the efficacy of CP in patients with COVID-19. Future research is necessary to fill the knowledge gap regarding prevention and treatment for patients with COVID-19 with CP while other therapeutics are being developed.

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Section: Mechanisms Of Actionmentioning

confidence: 99%

Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis

Peng¹,

Rhind²,

Beckett³

2021

JMIR Public Health Surveill

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“…By June 2020, the Wuhan originated D614 virus made a complete global transition to G614, probably to ensure its own survival 1 .Now, it has further evolved into more transmissible UK (B.1.1.7) and potentially more neutralization resistant South African (501Y.V2) strains 2,3,4 .…”

Section: Introductionmentioning

confidence: 99%

“…The UK variant is defined by nine spike protein mutations i.e, del 69-70, del 144, N501Y, A570D, D614G, P681H, T716I, S982A and D1118H 5 . The South African variant is defined by four spike protein mutations i.e, K417N, E484K, N501Y and D614G 3 . Another lineage (501Y.V3) has been idenfied in Manaus, Brazil defined by K417T, E484K and N501Y 6 .…”

Section: Introductionmentioning

confidence: 99%

“…It is necessary to study sequence variations constantly to control highly transmissible and vaccine-resistant strains. By June 2020, the Wuhan originated D614 virus made a complete global transition to G614, probably to ensure its own survival 1 .Now, it has further evolved into more transmissible UK (B.1.1.7) and potentially more neutralization resistant South African (501Y.V2) strains 2, 3, 4 . The UK variant is defined by nine spike protein mutations i.e, del 69-70, del 144, N501Y, A570D, D614G, P681H, T716I, S982A and D1118H 5 .…”

Section: Introductionmentioning

confidence: 99%

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Detection of SARS-CoV-2 N501Y mutation by RT-PCR to identify the UK and the South African strains in the population of South Indian state of Telangana

Ahmed

Juvvadi

Kalapala

et al. 2021

Preprint

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ObjectiveTo detect N501Y mutation of the SARS-CoV-2 spike protein by RT-PCR to distinguish (B.1.1.7) UK and (501Y.V2) South African strains from others in the population of Telangana and to determine its clinical implications.MethodsA primer-probe mix that specifically detects the mutated N501Y strain by real time RT-PCR was designed. 93 samples that were reported positive for COVID-19 by our laboratory in the month of February 2021 were tested using our own primer-probe mix for the presence of N501Y by RT-PCR. The results of RT-PCR were validated by Sanger sequencing in representative samples. Sanger sequencing of other defining spike mutations of B.1.1.7 (del 69-70, del 144, N501Y, A570D, D614G, P681H, T716I, S982A and D1118H) and 501Y.V2 (K417N, E484K, N501Y and D614G) was also investigated.FindingsOut of 93 COVID-19 positive samples, 12 samples are detected positive for N501Y by RT-PCR. Sanger sequencing of these 12 samples further confirmed the presence of N501Y and other mutations that are characteristic of UK strain (B.1.1.7). The South African strain (501Y.V2) is not detected in any of our samples in this study. But, the E484K mutation that is characteristic of 501Y.V2 is detected in one N501Y negative sample.ConclusionStrain-specific RT-PCR for N501Y was developed and validated with Sanger sequencing. Such strategy facilitates quick surveillance for more transmissible and more vaccine resistant strains.

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“…As per a study on evacuated people from China to Japan, asymptomatic ratio was nearly 30% (Nishiura et al 2020). Though SARS-Cov2 genome sequence, its mutant and their potential impact on disease management have been investigated (Wu et al 2020;Leung et al 2020;Li et al 2021;Starr et al 2021), 1 3 the molecular mechanism behind the prevalence of low viral load and asymptomatic cases is largely unexplored. Here we attempted an in silico dissection of the molecular peculiarities of the SARS-Cov2 viral genome using bioinformatic tools to develop a theoretical hypothesis behind the prevalence of asymptomatic cases in Covid-19.…”

Section: Introductionmentioning

confidence: 99%

Complexities in viral replication strategies as a potential explanation for prevalence of asymptomatic carriers in Covid-19 infections: analytical observation on SARS-Cov2 genome characteristics

Priyadarshi

Das

2021

Theory Biosci.

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Analytical observations (in silico) indicate molecular features of SARS-Cov2 genome that potentially explains the high prevalence of asymptomatic cases in Covid-19 pandemic. We observed that the virus maintains a low preference for 'GGG' codon for glycine (3%) in its genome. We also observed multiple putative introns of 26-44 nucleotide (nt) length in the genomic region between the coding regions of Nsp10 and RPol in the viral ORF1ab, like several other beta-coronaviruses of similar infectivity levels. It appears that the virus employs a dual strategy to ensure unhindered replication within the host. One of the strategies employ a (− )1 frameshift translation event through programmed ribosomal slippage at the ribosomal slippage site in the ORF1ab. The alternate strategy relies on intron excision to generate a read through frame. The presence of 'GGG' in this conserved ribosomal slippage site ensures adequate tRNA in cytoplasm to match the codon, implying no additional frameshift translation due to ribosomal stalling. With fewer replication events, viral load remains low and resulting in asymptomatic cases. We suggest that this strategy is the primary reason for the prevalence of asymptomatic cases in the disease, enabling the virus to spread rapidly.

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Differential efficiencies to neutralize the novel mutants B.1.1.7 and 501Y.V2 by collected sera from convalescent COVID-19 patients and RBD nanoparticle-vaccinated rhesus macaques

Cited by 24 publications

References 17 publications

Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis

Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis

Detection of SARS-CoV-2 N501Y mutation by RT-PCR to identify the UK and the South African strains in the population of South Indian state of Telangana

Complexities in viral replication strategies as a potential explanation for prevalence of asymptomatic carriers in Covid-19 infections: analytical observation on SARS-Cov2 genome characteristics

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