SARS-CoV-2 worldwide replication drives rapid rise and selection of mutations across the viral genome: a time-course study - potential challenge for vaccines and therapies.
TL;DR: In this paper, the authors examined >µ383,500 complete SARS-CoV-2 nucleotide sequences in GISAID (Global Initiative of Sharing All Influenza Data) with sampling dates extending until April 05, 2021.
Abstract: Scientists and the public were alarmed at the first large viral variant of SARS-CoV-2 reported in December 2020. We have followed the time course of emerging viral mutants and variants during the SARS-CoV-2 pandemic in ten countries on four continents. We examined > 383,500 complete SARS-CoV-2 nucleotide sequences in GISAID (Global Initiative of Sharing All Influenza Data) with sampling dates extending until April 05, 2021. These sequences originated from ten different countries: United Kingdom, South Africa, Brazil, United States, India, Russia, France, Spain, Germany, and China. Among the 77 to 100 novel mutations, some previously reported mutations waned and some of them increased in prevalence over time. VUI2012/01 (B.1.1.7) and 501Y.V2 (B.1.351), the so-called UK and South Africa variants, respectively, and two variants from Brazil, 484K.V2, now called P.1 and P.2, increased in prevalence. Despite lockdowns, worldwide active replication in genetically and socio-economically diverse populations facilitated selection of new mutations. The data on mutant and variant SARS-CoV-2 strains provided here comprise a global resource for easy access to the myriad mutations and variants detected to date globally. Rapidly evolving new variant and mutant strains might give rise to escape variants, capable of limiting the efficacy of vaccines, therapies, and diagnostic tests.
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TL;DR: In this article , the authors reviewed both SARS-CoV-2-induced host immune activation and vaccine-induced immune responses, highlighting the responses of immune memory cells that are key indicators of host immunity.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new beta coronavirus that emerged at the end of 2019 in the Hubei province of China. SARS-CoV-2 causes coronavirus disease 2019 (COVID-19) and was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. Herd or community immunity has been proposed as a strategy to protect the vulnerable, and can be established through immunity from past infection or vaccination. Whether SARS-CoV-2 infection results in the development of a reservoir of resilient memory cells is under investigation. Vaccines have been developed at an unprecedented rate and 7 408 870 760 vaccine doses have been administered worldwide. Recently emerged SARS-CoV-2 variants are more transmissible with a reduced sensitivity to immune mechanisms. This is due to the presence of amino acid substitutions in the spike protein, which confer a selective advantage. The emergence of variants therefore poses a risk for vaccine effectiveness and long-term immunity, and it is crucial therefore to determine the effectiveness of vaccines against currently circulating variants. Here we review both SARS-CoV-2-induced host immune activation and vaccine-induced immune responses, highlighting the responses of immune memory cells that are key indicators of host immunity. We further discuss how variants emerge and the currently circulating variants of concern (VOC), with particular focus on implications for vaccine effectiveness. Finally, we describe new antibody treatments and future vaccine approaches that will be important as we navigate through the COVID-19 pandemic.
127 citations
TL;DR: This study underscores the high diversity of theDelta variant between countries and identifies a list of amino acid mutations in the Delta variant’s proteome for probing the mechanistic basis of pathogenic features such as high viral loads, high transmissibility, and reduced susceptibility against neutralization by vaccines.
Abstract: The highly contagious Delta variant of SARS‐CoV‐2 has become a prevalent strain globally and poses a public health challenge around the world. While there has been extensive focus on understanding the amino acid mutations in the Delta variant’s Spike protein, the mutational landscape of the rest of the SARS‐CoV‐2 proteome (25 proteins) remains poorly understood. To this end, we performed a systematic analysis of mutations in all the SARS‐CoV‐2 proteins from nearly 2 million SARS‐CoV‐2 genomes from 176 countries/territories. Six highly prevalent missense mutations in the viral life cycle‐associated Membrane (I82T), Nucleocapsid (R203M, D377Y), NS3 (S26L), and NS7a (V82A, T120I) proteins are almost exclusive to the Delta variant compared to other variants of concern (mean prevalence across genomes: Delta = 99.74%, Alpha = 0.06%, Beta = 0.09%, and Gamma = 0.22%). Furthermore, we find that the Delta variant harbors a more diverse repertoire of mutations across countries compared to the previously dominant Alpha variant. Overall, our study underscores the high diversity of the Delta variant between countries and identifies a list of amino acid mutations in the Delta variant’s proteome for probing the mechanistic basis of pathogenic features such as high viral loads, high transmissibility, and reduced susceptibility against neutralization by vaccines.
18 citations
TL;DR: Sarma et al. as mentioned in this paper conducted in silico analysis of the ethanol extracted phytochemicals of Tulsi as inhibitors of SARS-CoV-2 (2019-nCoV) main protease with an approach to look into the possibility of covalent ligand binding with the catalytic residue Cys145, which makes the report unique.
Abstract: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compelled the scientific community to search for an effective drug that can cure or a vaccine that can prevent the disease. Alternatively, symptomatic treatment and traditional immunity boosters are prescribed. Holy Tulsi (Ocimum sanctum) has been known as an ancient remedy for cure of common cold and respiratory ailment. Several reports have come on virtual screening of phytochemicals including those of Tulsi against various enzymes of the virus. We undertook in silico analysis of the ethanol extracted phytochemicals of Tulsi as inhibitors of SARS-CoV-2 (2019-nCoV) main protease with an approach to look into the possibility of covalent ligand binding with the catalytic residue Cys145, which makes the report unique. The results suggest that the flavonoids and polyphenolic compounds of Tulsi, have potential to covalently bind to the catalytic residue Cys145 of main protease and irreversibly inhibit the viral enzyme. Luteolin-7-O-glucuronide is specially considered for its optimum properties, namely, low toxicity (LD50 5000 mg/kg body weight), high drug-likeness score (0.71), the active site binding free energy (ΔGbind) -19.19 kcal/mol by GBSA method and covalent binding energy -24.23 kcal/mol. Further experimental validations are required to establish the theoretical findings.Communicated by Ramaswamy H. Sarma.
12 citations
University of South Florida1, Universidad Católica de Valencia San Vicente Mártir2, University of Otago3, Yarmouk University4, King Abdulaziz University5, Mayo Clinic6, Indian Institute of Chemical Technology7, Minia University8, University of Texas Health Science Center at San Antonio9, Indian Statistical Institute10, Patna University11, Tulane University12, Monterrey Institute of Technology and Higher Education13, Ulster University14, Kyoto University15, Universidade Federal de Minas Gerais16, University of Padua17, University of the Witwatersrand18
TL;DR: In this article, the authors highlight 128 single mutations and 35 co-occurring mutations in the unique SARS-CoV-2 ORF10 variants and the possible predicted effects of these mutations and cooccurrence mutations on the secondary structure of ORF 10 variants and host protein interactomes are presented.
10 citations
TL;DR: In this article, the authors assessed VOC B.1.7 and found that the VOC had similar replication kinetics as compared to wt-S614G in human airway epithelial cultures.
Abstract: Emerging variants of concern (VOCs) drive the SARS-CoV-2 pandemic. We assessed VOC B.1.1.7, now prevalent in several countries, and VOC B.1.351, representing the greatest threat to populations with immunity to the early SARS-CoV-2 progenitors. B.1.1.7 showed a clear fitness advantage over the progenitor variant (wt-S614G) in ferrets and two mouse models, where the substitutions in the spike glycoprotein were major drivers for fitness advantage. In the “superspreader” hamster model, B.1.1.7 and wt-S614G had comparable fitness, whereas B.1.351 was outcompeted. The VOCs had similar replication kinetics as compared to wt-S614G in human airway epithelial cultures. Our study highlights the importance of using multiple models for complete fitness characterization of VOCs and demonstrates adaptation of B.1.1.7 towards increased upper respiratory tract replication and enhanced transmission in vivo. Summary sentence B.1.1.7 VOC outcompetes progenitor SARS-CoV-2 in upper respiratory tract replication competition in vivo.
10 citations
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TL;DR: The outbreak of the 2019 novel coronavirus disease (COVID-19) has induced a considerable degree of fear, emotional stress and anxiety among individuals around the world.
Abstract: The outbreak of the 2019 novel coronavirus disease (COVID-19) has induced a considerable degree of fear, emotional stress and anxiety among individuals around t
8,336 citations
TL;DR: A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic, and it is found that the G614 variant grows to higher titer as pseudotyped virions.
3,302 citations
TL;DR: This poster presents a poster presenting a poster presented at the 2016 International Conference of the Association for the Study of Viral Influenza and its Disruption in China, where it was presented for the first time.
Abstract: Yuelong Shu1, John McCauley2 1. WHO Collaborating Center for Reference and Research on Influenza, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China 2. WHO Collaborating Centre for Reference and Research on Influenza, Crick Worldwide Influenza Centre, the Francis Crick Institute, London, United Kingdom
2,306 citations
TL;DR: A rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread and is designed to provide a real-time bird’s-eye view of the diversity of the hundreds of thousands of genome sequences collected worldwide.
Abstract: The ongoing pandemic spread of a new human coronavirus, SARS-CoV-2, which is associated with severe pneumonia/disease (COVID-19), has resulted in the generation of tens of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. Here, we present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread. Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and delabelling virus lineages that become unobserved and hence are probably inactive. By focusing on active virus lineages and those spreading to new locations, this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2.
2,093 citations
10 Jan 2017
TL;DR: The article finds that the Global Initiative on Sharing All Influenza Data contributes to global health in at least five ways: collating the most complete repository of high‐quality influenza data in the world; facilitating the rapid sharing of potentially pandemic virus information during recent outbreaks; supporting the World Health Organization's biannual seasonal flu vaccine strain selection process; developing informal mechanisms for conflict resolution around the sharing of virus data.
Abstract: The international sharing of virus data is critical for protecting populations against le-thal infectious disease outbreaks. Scientists must rapidly share information to assessthe nature of the threat and develop new medical countermeasures. Governmentsneed the data to trace the extent of the outbreak, initiate public health responses,and coordinate access to medicines and vaccines. Recent outbreaks suggest, however,that the sharing of such data cannot be taken for granted – making the timely inter-national exchange of virus data a vital global challenge. This article undertakes thefirst analysis of the Global Initiative on Sharing All Influenza Data as an innovativepolicy effort to promote the international sharing of genetic and associated influenzavirus data. Based on more than 20 semi-structured interviews conducted with key in-formants in the international community, coupled with analysis of a wide range ofprimary and secondary sources, the article finds that the Global Initiative on SharingAll Influenza Data contributes to global health in at least five ways: (1) collating themost complete repository of high-quality influenza data in the world; (2) facilitatingthe rapid sharing of potentially pandemic virus information during recent outbreaks;(3) supporting the World Health Organization’s biannual seasonal flu vaccine strainselection process; (4) developing informal mechanisms for conflict resolution aroundthe sharing of virus data; and (5) building greater trust with several countries key toglobal pandemic preparedness.
1,570 citations