COVID-19 vaccines: early success and remaining challenges

Bar-Zeev, Naor; Inglesby, Tom

doi:10.1016/s0140-6736(20)31867-5

Cited by 34 publications

(51 citation statements)

References 7 publications

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“…The COVID-19 pandemic caused by the SARS-CoV-2 virus has sparked extensive efforts to map molecular details of its life cycle to drive vaccine and therapeutic discovery ( Bar-Zeev and Inglesby, 2020 ). SARS-CoV-2 belongs to the family of Coronaviridae, which includes other human pathogens including common cold-causing viruses (hCoV-OC43, HKU, and 229E), SARS, and MERS-CoV ( Corman et al, 2018 ; St-Jean et al, 2004 ; Lau et al, 2006 ; Warnes et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets

Raghuvamsi

Tulsian

Samsudin

et al. 2021

eLife

112

129

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The Spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface ACE2 receptors. How ACE2 binding activates proteolysis of S protein is unknown. Here, using amide hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations, we have mapped the S:ACE2 interaction interface and uncovered long-range allosteric propagation of ACE2 binding to sites necessary for host-mediated proteolysis of S protein, critical for viral host entry. Unexpectedly, ACE2 binding enhances dynamics at a distal S1/S2 cleavage site and flanking protease docking site ~27 Å away while dampening dynamics of the stalk hinge (central helix and heptad repeat) regions ~130 Å away. This highlights that the stalk and proteolysis sites of the S protein are dynamic hotspots in the pre-fusion state. Our findings provide a dynamics map of the S:ACE2 interface in solution and also offer mechanistic insights into how ACE2 binding is allosterically coupled to distal proteolytic processing sites and viral-host membrane fusion. Our findings highlight protease docking sites flanking the S1/S2 cleavage site, fusion peptide and heptad repeat 1 (HR1) as alternate allosteric hotspot targets for potential therapeutic development.

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Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets

Raghuvamsi

Tulsian

Samsudin

et al. 2021

eLife

112

129

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“…As of December 30, 2020, over 81 million people were infected with COVID-19, and more than 1.7 million deaths were reported. Many health institutions are attempting to produce effective vaccines against this virus infection, and several are now in the final stages of development before their application to human populations [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Isolating SARS-CoV-2 Strains From Countries in the Same Meridian: Genome Evolutionary Analysis

Mastriani¹,

Rakov²,

Liu³

2021

JMIR Bioinformatics Biotechnol

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Background COVID-19, caused by the novel SARS-CoV-2, is considered the most threatening respiratory infection in the world, with over 40 million people infected and over 0.934 million related deaths reported worldwide. It is speculated that epidemiological and clinical features of COVID-19 may differ across countries or continents. Genomic comparison of 48,635 SARS-CoV-2 genomes has shown that the average number of mutations per sample was 7.23, and most SARS-CoV-2 strains belong to one of 3 clades characterized by geographic and genomic specificity: Europe, Asia, and North America. Objective The aim of this study was to compare the genomes of SARS-CoV-2 strains isolated from Italy, Sweden, and Congo, that is, 3 different countries in the same meridian (longitude) but with different climate conditions, and from Brazil (as an outgroup country), to analyze similarities or differences in patterns of possible evolutionary pressure signatures in their genomes. Methods We obtained data from the Global Initiative on Sharing All Influenza Data repository by sampling all genomes available on that date. Using HyPhy, we achieved the recombination analysis by genetic algorithm recombination detection method, trimming, removal of the stop codons, and phylogenetic tree and mixed effects model of evolution analyses. We also performed secondary structure prediction analysis for both sequences (mutated and wild-type) and “disorder” and “transmembrane” analyses of the protein. We analyzed both protein structures with an ab initio approach to predict their ontologies and 3D structures. Results Evolutionary analysis revealed that codon 9628 is under episodic selective pressure for all SARS-CoV-2 strains isolated from the 4 countries, suggesting it is a key site for virus evolution. Codon 9628 encodes the P0DTD3 (Y14_SARS2) uncharacterized protein 14. Further investigation showed that the codon mutation was responsible for helical modification in the secondary structure. The codon was positioned in the more ordered region of the gene (41-59) and near to the area acting as the transmembrane (54-67), suggesting its involvement in the attachment phase of the virus. The predicted protein structures of both wild-type and mutated P0DTD3 confirmed the importance of the codon to define the protein structure. Moreover, ontological analysis of the protein emphasized that the mutation enhances the binding probability. Conclusions Our results suggest that RNA secondary structure may be affected and, consequently, the protein product changes T (threonine) to G (glycine) in position 50 of the protein. This position is located close to the predicted transmembrane region. Mutation analysis revealed that the change from G (glycine) to D (aspartic acid) may confer a new function to the protein—binding activity, which in turn may be responsible for attaching the virus to human eukaryotic cells. These findings can help design in vitro experiments and possibly facilitate a vaccine design and successful antiviral strategies.

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“…To date, no effective treatment has been demonstrated to radically change the natural history of SARS-CoV-2 infection [ 7 ], and several vaccination strategies are still under development [ 8 ]; on the other hand, flu vaccination is able to decrease both the incidence rates of influenza and to moderate the severity of the disease in case of infection. Moreover, a remarkable decrease in morbidity for pneumonia, respiratory, and cardiovascular complications and consequent risk of hospitalization and death has been consistently reported in the literature [ 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Missed Opportunities of Flu Vaccination in Italian Target Categories: Insights from the Online EPICOVID 19 Survey

et al. 2020

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We aimed to assess the reported rate of flu vaccination in the 2019/2020 season for respondents to the Italian nationwide online EPICOVID 19 survey. A national convenience sample of volunteers aged 18 or older was assessed between 13 April and 2 June 2020. Flu vaccine rates were calculated for all classes of age. The association between the independent variables and the flu vaccine was assessed by applying a multivariable binary logistic regression model. Of the 198,822 respondents, 41,818 (21.0%) reported having received a flu vaccination shot during the last influenza season. In particular, 15,009 (53.4%) subjects aged 65 years or older received a flu vaccination shot. Being 65 years aged or older (Adjusted Odds Ratios (aOR) 3.06, 95% Confidence Interval (CI) 2.92–3.20) and having a high education level (aOR 1.34. 95%CI 1.28–1.41) were independently associated to flu vaccination. Heart and lung diseases were the morbidities associated with the higher odds of being vaccinated (aOR 1.97 (95%CI 1.86–2.09) and aOR 1.92 (95%CI 1.84–2.01), respectively). Nursing home residents aged ≥ 65 years showed lower odds of being vaccinated (aOR 0.39 (95%CI 0.28–0.54)). Our data indicate the need for an urgent public heath effort to fill the gap of missed vaccination opportunities reported in the past flu seasons.

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COVID-19 vaccines: early success and remaining challenges

Cited by 34 publications

References 7 publications

SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets

SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets

Isolating SARS-CoV-2 Strains From Countries in the Same Meridian: Genome Evolutionary Analysis

Missed Opportunities of Flu Vaccination in Italian Target Categories: Insights from the Online EPICOVID 19 Survey

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