Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function.
Tzu-Jing Yang,Tzu-Jing Yang,Pei-Yu Yu,Yuan-Chih Chang,Kang-Hao Liang,Hsian-Cheng Tso,Meng-Ru Ho,Wan-Yu Chen,Hsiu-Ting Lin,Han-Chung Wu,Shang-Te Danny Hsu,Shang-Te Danny Hsu +11 more
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In this paper, the spike protein of SARS-CoV-2 was analyzed in the apo and ACE2-bound forms and three RBDs were found to be engaged in ACE2 binding.Abstract:
The B.1.1.7 variant of SARS-CoV-2 first detected in the UK harbors amino-acid substitutions and deletions in the spike protein that potentially enhance host angiotensin conversion enzyme 2 (ACE2) receptor binding and viral immune evasion. Here we report cryo-EM structures of the spike protein of B.1.1.7 in the apo and ACE2-bound forms. The apo form showed one or two receptor-binding domains (RBDs) in the open conformation, without populating the fully closed state. All three RBDs were engaged in ACE2 binding. The B.1.1.7-specific A570D mutation introduces a molecular switch that could modulate the opening and closing of the RBD. The N501Y mutation introduces a π-π interaction that enhances RBD binding to ACE2 and abolishes binding of a potent neutralizing antibody (nAb). Cryo-EM also revealed how a cocktail of two nAbs simultaneously bind to all three RBDs, and demonstrated the potency of the nAb cocktail to neutralize different SARS-CoV-2 pseudovirus strains, including B.1.1.7.read more
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Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study
TL;DR: In this paper , the three-dimensional structure of the Spike RBD domain of Omicron variant was constructed by incorporating 15 amino acid substitutions to the Native Spike (S) structure and structural changes were compared that of the Native S.
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Electrostatic Features for the Receptor Binding Domain of SARS-COV-2 Wildtype and Its Variants. Compass to the Severity of the Future Variants with the Charge-Rule
TL;DR: In this article , the main electrostatic features involved in the interaction of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with the human receptor Angiotensin-converting enzyme 2 (ACE2).
Journal ArticleDOI
Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins
TL;DR: In this article , the host cell membrane-binding surfaces of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike variants Alpha, Beta, Gamma, Delta, Epsilon, Kappa, and Omicron as well as pangolin and bat relatives were analyzed.
Journal ArticleDOI
(+)-Usnic acid and its salts, inhibitors of SARS‐CoV‐2, identified by using in silico methods and in vitro assay
Eunseok Oh,Weihong Wang,Kyu Hyung Park,Chan-Yung Park,Youbin Cho,Juni Lee,Eunmo Kang,Heonjoong Kang +7 more
TL;DR: In this paper , the authors have investigated the inhibitors of SARS-CoV-2 protein targets by high-throughput virtual screening using a marine natural products database and selected (+)-usnic acid as a suitable hit.
Journal ArticleDOI
Variant-specific deleterious mutations in the SARS-CoV-2 genome reveal immune responses and potentials for prophylactic vaccine development
Md. Aminul Islam,Shatila Shahi,Abdullah Al Marzan,Mohammad Amin,Mohammad Al Hasan,M. Nazmul Hoque,Ajit Ghosh,A Barua,Abbas Khan,Kuldeep Dhama,Chiranjib Chakraborty,S. Bhattacharya,Dong-Qing Wei +12 more
Abstract: Introduction: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has had a disastrous effect worldwide during the previous three years due to widespread infections with SARS-CoV-2 and its emerging variations. More than 674 million confirmed cases and over 6.7 million deaths have been attributed to successive waves of SARS-CoV-2 infections as of 29th January 2023. Similar to other RNA viruses, SARS-CoV-2 is more susceptible to genetic evolution and spontaneous mutations over time, resulting in the continual emergence of variants with distinct characteristics. Spontaneous mutations of SARS-CoV-2 variants increase its transmissibility, virulence, and disease severity and diminish the efficacy of therapeutics and vaccines, resulting in vaccine-breakthrough infections and re-infection, leading to high mortality and morbidity rates. Materials and methods: In this study, we evaluated 10,531 whole genome sequences of all reported variants globally through a computational approach to assess the spread and emergence of the mutations in the SARS-CoV-2 genome. The available data sources of NextCladeCLI 2.3.0 (https://clades.nextstrain.org/) and NextStrain (https://nextstrain.org/) were searched for tracking SARS-CoV-2 mutations, analysed using the PROVEAN, Polyphen-2, and Predict SNP mutational analysis tools and validated by Machine Learning models. Result: Compared to the Wuhan-Hu-1 reference strain NC 045512.2, genome-wide annotations showed 16,954 mutations in the SARS-CoV-2 genome. We determined that the Omicron variant had 6,307 mutations (retrieved sequence:1947), including 67.8% unique mutations, more than any other variant evaluated in this study. The spike protein of the Omicron variant harboured 876 mutations, including 443 deleterious mutations. Among these deleterious mutations, 187 were common and 256 were unique non-synonymous mutations. In contrast, after analysing 1,884 sequences of the Delta variant, we discovered 4,468 mutations, of which 66% were unique, and not previously reported in other variants. Mutations affecting spike proteins are mostly found in RBD regions for Omicron, whereas most of the Delta variant mutations drawn to focus on amino acid regions ranging from 911 to 924 in the context of epitope prediction (B cell & T cell) and mutational stability impact analysis protruding that Omicron is more transmissible. Discussion: The pathogenesis of the Omicron variant could be prevented if the deleterious and persistent unique immunosuppressive mutations can be targeted for vaccination or small-molecule inhibitor designing. Thus, our findings will help researchers monitor and track the continuously evolving nature of SARS-CoV-2 strains, the associated genetic variants, and their implications for developing effective control and prophylaxis strategies.
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