Loss of orf3b in the circulating SARS-CoV-2 strains

Lam, Joy-Yan; Yuen, Chun-Kit; Ip, Jonathan Daniel; Wong, Wan-Man; To, Kelvin Kai-Wang; Yuen, Kwok‐Yung; Kok, Kin‐Hang

doi:10.1080/22221751.2020.1852892

Cited by 49 publications

(40 citation statements)

References 27 publications

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“…First, it may cause failure of treatment by shifting the protein-binding interface and destroying drug-targeting sites . Secondly, it leads to formation of an early stop codon to orf3b after amino acid 13 (Δ3b), resulting in a truncated ORF3b protein with consequent loss of interferon antagonism (Lam et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Mutation Landscape of SARS COV2 in Africa

Nassir¹,

Musanabaganwa

Mwikarago

2020

Preprint

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COVID-19 disease has had a relatively less severe impact in Africa. To understand the role of SARS CoV2 mutations on COVID-19 disease in Africa, we analysed 282 complete nucleotide sequences from African isolates deposited in the NCBI Virus Database. Sequences were aligned against the prototype Wuhan sequence (GenBank accession: NC_045512.2) in BWA v. 0.7.17. SAM and BAM files were created, sorted and indexed in SAMtools v. 1.10 and marked for duplicates using Picard v. 2.23.4. Variants were called with mpileup in BCFtools v. 1.11. Phylograms were created using Mr. Bayes v 3.2.6. A total of 2,349 single nucleotide polymorphism (SNP) profiles across 294 sites were identified. Clades associated with severe disease in the United States, France, Italy, and Brazil had low frequencies in Africa (L84S=2.5%, L3606F=1.4%, L3606F/V378I/=0.35, G251V=2%). Sub Saharan Africa (SSA) accounted for only 3% of P323L and 4% of Q57H mutations in Africa. Comparatively low infections in SSA were attributed to the low frequency of the D614G clade in earlier samples (25% vs 67% global). Higher disease burden occurred in countries with higher D614G frequencies (Egypt=98%, Morocco=90%, Tunisia=52%, South Africa) with D614G as the first confirmed case. V367F, D364Y, V483A and G476S mutations associated with efficient ACE2 receptor binding and severe disease were not observed in Africa. 95% of all RdRp mutations were deaminations leading to CpG depletion and possible attenuation of virulence. More genomic and experimental studies are needed to increase our understanding of the temporal evolution of the virus in Africa, clarify our findings, and reveal hot spots that may undermine successful therapeutic and vaccine interventions.

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Section: Discussionmentioning

confidence: 99%

Mutation Landscape of SARS COV2 in Africa

Nassir¹,

Musanabaganwa

Mwikarago

2020

Preprint

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“…It is possible that the interest for antibodies to SARS-CoV-2 internal proteins will grow with the rollout of sub-unit Spike only vaccines, in order to allow the distinction between SARS-CoV-2 past exposure and vaccination in specific populations and to create an estimated date of exposure given the unique rate of waning of different specificities. The emergence of certain viral mutants such as the ORF8 truncations 34 or recent ORF3b deletions 35 could modify the contributions of certain ORFs, their antibodies responses could also be used for epidemiology studies on the insurgence of different strains of the virus.…”

Section: Our Cohort Did Not Include Any Case Of Multi-inflammatory Symentioning

confidence: 99%

The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children

Hachim

Kavian

et al. 2021

Preprint

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BackgroundChildren are less clinically affected by SARS-CoV-2 infection than adults with the majority of cases being mild or asymptomatic and the differences in infection outcomes are poorly understood. The kinetics, magnitude and landscape of the antibody response may impact the clinical severity and serological diagnosis of COVID-19. Thus, a comprehensive investigation of the antibody landscape in children and adults is needed.MethodsWe tested 254 plasma from 122 children with symptomatic and asymptomatic SARS-CoV-2 infections in Hong Kong up to 206 days post symptom onset, including 146 longitudinal samples from 58 children. Adult COVID-19 patients and pre-pandemic controls were included for comparison. We assessed antibodies to a 14-wide panel of SARS-CoV-2 structural and accessory proteins by Luciferase Immunoprecipitation System (LIPS).FindingsChildren have lower levels of Spike and Nucleocapsid antibodies than adults, and their cumulative humoral response is more expanded to accessory proteins (NSP1 and Open Reading Frames (ORFs)). Sensitive serology using the three N, ORF3b, ORF8 antibodies can discriminate COVID-19 in children. Principal component analysis revealed distinct serological signatures in children and the highest contribution to variance were responses to non-structural proteins ORF3b, NSP1, ORF7a and ORF8. Longitudinal sampling revealed maintenance or increase of antibodies for at least 6 months, except for ORF7b antibodies which showed decline. It was interesting to note that children have higher antibody responses towards known IFN antagonists: ORF3b, ORF6 and ORF7a. The diversified SARS-CoV-2 antibody response in children may be an important factor in driving control of SARS-CoV-2 infection.

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“…Interestingly, circulating variants with loss-of-function deletions in SARS-CoV-2 ORF3b, ORF7a/7b, and ORF8 have been found, indicating that these are not absolutely essential for viral infection and may be remnants required for infection of an unidentified intermediate host (31)(32)(33)(34). ORF9b, an accessory protein translated from an alternative open reading frame within the N gene, interacts with the host mitochondrial import receptor protein TOM70, and suppresses type I interferon response (30,35).…”

Section: Taxonomy Genomic Organisation and Replication Cycle Of Sarmentioning

confidence: 99%

Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic

Sridhar

Chiu

et al. 2021

Emerging Microbes & Infections

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257

189

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Without modern medical management and vaccines, the severity of the Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome(SARS) coronavirus 2 (SARS-CoV-2) might approach the magnitude of 1894-plague (12 million deaths) and 1918-A(H1N1) influenza (50 million deaths) pandemics. The COVID-19 pandemic was heralded by the 2003 SARS epidemic which led to the discovery of human and civet SARS-CoV-1, bat SARS-related-CoVs, Middle East respiratory syndrome(MERS)-related bat CoV HKU4 and HKU5, and other novel animal coronaviruses. The suspected animal-to-human jumping of 4 betacoronaviruses including the human coronaviruses OC43(1890), SARS-CoV-1(2003), MERS-CoV(2012), and SARS-CoV-2(2019) indicates their significant pandemic potential. The presence of a large reservoir of coronaviruses in bats and other wild mammals, culture of mixing and selling them in urban markets with suboptimal hygiene, habit of eating exotic mammals in highly populated areas, and the rapid and frequent air traffic from these areas are perfect ingredients for brewing rapidly exploding epidemics. The possibility of emergence of a hypothetical SARS-CoV-3 or other novel viruses from animals or laboratories, and therefore needs for global preparedness should not be ignored. We reviewed representative publications on the epidemiology, virology, clinical manifestations, pathology, laboratory diagnostics, treatment, vaccination and infection control of COVID-19 as of 20 January 2021, which is one year after person-to-person transmission of SARS-CoV-2 was announced. The difficulties of mass testing, labour-intensive contact tracing, importance of compliance to universal masking, low efficacy of antiviral treatment for severe disease, possibilities of vaccine or antiviral-resistant virus variants and SARS-CoV-2 becoming another common cold coronavirus are discussed. The chronology of the pandemic An outbreak of acute community-acquired atypical pneumonia of unknown aetiology was reported in Wuhan, the capital of Hubei province in central China, in December 2019. The initial cluster of cases was related to the Huanan seafood wholesale market where wild game animals were also sold (1). During subsequent investigation, severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) was detected in 33 out of 585 environmental samples taken from the market (2). However, 45% of the cases with onset before 1 January 2020 had no apparent link to this market (3). Retrospective molecular clock inference studies using phylogenetic analysis suggested that the earliest cases likely emerged between October and November 2019 (4, 5). The culprit virus was identified using next-generation sequencing on bronchoalveolar lavage fluids of three Wuhan patients (6). The complete genome sequences of SARS-CoV-2 clustered in a distinct clade from SARS-CoV within the genus Sarbecovirus. The draft genome sequence was released on 10 Jan 2020, 10 days after the outbreak was announced. As an escalating number of local cases was reported in Wuhan, a f...

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Loss of orf3b in the circulating SARS-CoV-2 strains

Cited by 49 publications

References 27 publications

Mutation Landscape of SARS COV2 in Africa

Mutation Landscape of SARS COV2 in Africa

The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children

Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic

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