scholarly journals In Silico Investigation of the New UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 Variants with a Focus at the ACE2–Spike RBD Interface

2021 ◽  
Vol 22 (4) ◽  
pp. 1695
Author(s):  
Bruno O. Villoutreix ◽  
Vincent Calvez ◽  
Anne-Geneviève Marcelin ◽  
Abdel-Majid Khatib
Keyword(s):  
Amino Acid ◽  
South African ◽  
In Silico ◽  
Neutralizing Antibodies ◽  
Viral Escape ◽  
Spike Protein ◽  
Amino Acid Substitutions ◽  
The South ◽  
African Strain ◽  
The Uk

SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually in part due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor, several in silico methods and numerous experimental data reported recently to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both the UK and South African strains) should be favorable for the interaction with ACE2, while the K417N and E484K substitutions (South African strain) would seem neutral or even unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the K417N and E484K Spike replacements with regard to ACE2 binding. Our finding suggests that the UK strain should have higher affinity toward ACE2 and therefore likely increased transmissibility and possibly pathogenicity. If indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions located outside the direct Spike–ACE2 interface but not so much to the K417N and E484K replacements. Yet, it should be noted that amino acid changes at Spike position 484 can lead to viral escape from neutralizing antibodies. Further, these amino acid substitutions do not seem to induce major structural changes in this region of the Spike protein. This structure–function study allows us to rationalize some observations made for the UK strain but raises questions for the South African strain.

scholarly journals In silico investigation of the new UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 variants with a focus at the ACE2-Spike RBD interface

2021 ◽  
Author(s):  
Bruno O. Villoutreix ◽  
Vincent Calvez ◽  
Anne-Genevieve Marcelin ◽  
Abdel-Majid Khatib
Keyword(s):  
Amino Acid ◽  
South African ◽  
In Silico ◽  
3D Structure ◽  
List Type ◽  
The South ◽  
Angiotensin Converting Enzyme 2 ◽  
African Strain ◽  
The Uk ◽  
Experimental Structure

AbstractSARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor and several in silico methods to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both UK and South African strains) should be favorable for the interaction with ACE2 while the K417N and E484K substitutions (South African) would seem unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the predicted less favorable (regarding binding) K417N and E484K Spike replacements. Our finding suggests that, if indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions outside the direct Spike-ACE2 interface.HihglightsTransmission of the UK and possibly South African SARS-CoV-2 strains appears substantially increased compared to other variantsThis could be due, in part, to increased affinity between the variant Spike proteins and ACE2We investigated in silico the 3D structure of the Spike-ACE2 complex with a focus on Spike K417N, E484K and N501YThe N501Y substitution is predicted to increase the affinity toward ACE2 (UK strain) with subsequent enhanced transmissibility and possibly pathogenicityAdditional substitutions at positions 417 and 484 (South African strain) may pertub the interaction with ACE2 raising questions about transmissibility and pathogenicity

scholarly journals L18F substrain of SARS-CoV-2 VOC-202012/01 is rapidly spreading in England

2021 ◽  
Author(s):  
Frederic Grabowski ◽  
Marek Kochańczyk ◽  
Tomasz Lipniacki
Keyword(s):  
Molecular Evolution ◽  
South African ◽  
Receptor Binding ◽  
Growth Rates ◽  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Binding Motif ◽  
Viral Genomes ◽  
African Strain ◽  
Escape Mutants

AbstractThe Variant of Concern (VOC)-202012/01 (also known as B.1.1.7) is a rapidly growing lineage of SARS-CoV-2. In January 2021, VOC-202012/01 constituted about 80% of SARS-CoV-2 genomes sequenced in England and was present in 27 out of 29 countries that reported at least 50 viral genomes. As this strain will likely spread globally towards fixation, it is important to monitor its molecular evolution. Based on GISAID data we systematically estimated growth rates of mutations acquired by the VOC lineage to find that L18F substitution in viral spike protein has initiated a substrain characterized by replicative advantage of 1.70 [95% CI: 1.56–1.96] in relation to the remaining VOC-202012/01 substrains. The L18F mutation is of significance because when recently analyzed in the context of the South African strain 501Y.V2 it has been found to compromise binding of neutralizing antibodies. We additionally indicate three mutations that were acquired by VOC-202012/01 in the receptor binding motif of spike, specifically E484K, F490S, and S494P, that may also give rise to escape mutants. Such mutants may hinder efficiency of existing vaccines and expand in response to the increasing after-infection or vaccine-induced seroprevalence.

scholarly journals 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

2021 ◽  
Author(s):  
Safaa Muneer Ahmed ◽  
Smita Rao Juvvadi ◽  
Rakesh Kalapala ◽  
Jagadeesh Babu Sreemanthula
Keyword(s):  
South African ◽  
Sanger Sequencing ◽  
Rt Pcr ◽  
The South ◽  
African Strain ◽  
South Indian ◽  
Indian State ◽  
Resistant Strains ◽  
The Uk ◽  
Representative Samples

AbstractObjectiveTo 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.

scholarly journals Structural Analysis of Spike Protein Mutations in an Emergent SARS-CoV-2 Variant from the Philippines

2021 ◽  
Author(s):  
Neil Andrew D. Bascos ◽  
Denise Mirano-Bascos ◽  
Cynthia P. Saloma
Keyword(s):  
South African ◽  
Neutralizing Antibodies ◽  
Clinical Investigation ◽  
The Philippines ◽  
Molecular Surface ◽  
Spike Protein ◽  
Structure Stability ◽  
Whole Genome ◽  
Surface Character ◽  
The Uk

AbstractA SARS-CoV-2 emergent lineage with multiple signature mutations in the Spike protein region was recently reported with cases centered in Cebu Island, Philippines. Whole genome sequencing revealed that the 33 samples with the Ph-B.1.1.28 emergent variant merit further investigation as they all contain the E484K, N501Y, and P681H Spike mutations previously found in other variants of concern such as the South African B.1.351, the Brazil P.1 and the UK B.1.1.7 variants. This is the first known report of these mutations co-occurring in the same virus. The possible implications of the mutations found in the Spike protein were analyzed for their potential effects on structure, stability, and molecular surface character. The analysis suggests that these mutations could significantly impact the possible interactions of the Spike protein monomer with the ACE2 receptor and neutralizing antibodies and warrants further clinical investigation. Some of the mutations affecting the N and C terminal domains may have effects on Spike monomer and trimer stability. This report provides insights on relevant targets for the design of future diagnostics, therapeutics and vaccines against the evolving SARS-CoV-2 variants in the Philippines.

scholarly journals Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells

PLoS ONE ◽  
2009 ◽  
Vol 4 (7) ◽  
pp. e6130 ◽  
Author(s):  
Yoshiyuki Yamada ◽  
Xiao Bo Liu ◽  
Shou Guo Fang ◽  
Felicia P. L. Tay ◽  
Ding Xiang Liu
Keyword(s):  
Amino Acid ◽  
Cell Fusion ◽  
Cultured Cells ◽  
Spike Protein ◽  
Amino Acid Substitutions ◽  
Fusion Activity ◽  
Cell Cell

scholarly journals Introduction of the South African SARS-CoV-2 variant 501Y.V2 into the UK

2021 ◽  
Author(s):  
Julian W. Tang ◽  
Oliver T.R. Toovey ◽  
Kirsty N. Harvey ◽  
David D.S. Hui
Keyword(s):  
South African ◽  
The South ◽  
The Uk

scholarly journals Reflections on a field across time and space: the emergent medical and health humanities in South Africa

2018 ◽  
Vol 44 (4) ◽  
pp. 263-269 ◽  
Author(s):  
Victoria Jane Hume ◽  
Megan Wainwright
Keyword(s):  
South Africa ◽  
South African ◽  
Cross Cultural ◽  
The South ◽  
Health Humanities ◽  
Cultural Experience ◽  
The North ◽  
Qualitative Evidence ◽  
The Uk ◽  
Personal Reflections

In this paper, we draw on our own cross-cultural experience of engaging with different incarnations of the medical and health humanities (MHH) in the UK and South Africa to reflect on what is distinct and the same about MHH in these locations. MHH spaces, whether departments, programmes or networks, have espoused a common critique of biomedical dualism and reductionism, a celebration of qualitative evidence and the value of visual and performative arts for their research, therapeutic and transformative social potential. However, there have also been differences, and importantly a different ‘identity’ among some leading South African scholars and practitioners, who have felt that if MHH were to speak from the South as opposed to the North, they would say something quite different. We seek to contextualise our personal reflections on the development of the field in South Africa over recent years within wider debates about MHH in the context of South African academia and practice, drawing in part on interviews conducted by one of the authors with South African researchers and practitioners and our own reflections as ‘Northerners’ in the ‘South’.

Construction and immunogenic studies of a mFc fusion receptor binding domain (RBD) of spike protein as a subunit vaccine against SARS-CoV-2 infection

2020 ◽  
Vol 56 (61) ◽  
pp. 8683-8686 ◽  
Author(s):  
Xiaoxiao Qi ◽  
Bixia Ke ◽  
Qian Feng ◽  
Deying Yang ◽  
Qinghai Lian ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fusion Protein ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Humoral And Cellular Immunity ◽  
A Subunit

Herein, we report that a recombinant fusion protein, containing a 457 amino acid SARS-CoV-2 receptor binding domain and a mouse IgG1 Fc domain, could induce highly potent neutralizing antibodies and stimulate humoral and cellular immunity in mice.

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