scholarly journals MERS-CoV spike protein: a key target for antivirals

2016 ◽  
Vol 21 (2) ◽  
pp. 131-143 ◽  
Author(s):  
Lanying Du ◽  
Yang Yang ◽  
Yusen Zhou ◽  
Lu Lu ◽  
Fang Li ◽  
...  
Keyword(s):  
Protein A ◽  
Spike Protein

scholarly journals A FOUNDER EFFECT LED EARLY SARS-COV-2 TRANSMISSION IN SPAIN

2020 ◽  
Author(s):  
Francisco Díez-Fuertes ◽  
María Iglesias-Caballero ◽  
Javier García Pérez ◽  
Sara Monzón ◽  
Pilar Jiménez ◽  
...  
Keyword(s):  
Founder Effect ◽  
Phylogenetic Analyses ◽  
Protein A ◽  
Spike Protein ◽  
Recent Common Ancestor ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Most Recent Common Ancestor ◽  
Fitness Advantage

SARS-CoV-2 whole-genome analysis has identified five large clades worldwide, emerged in 2019 (19A and 19B) and in 2020 (20A, 20B and 20C). This study aims to analyze the diffusion of SARS-CoV-2 in Spain using maximum likelihood phylogenetic and Bayesian phylodynamic analyses. The most recent common ancestor (MRCA) of the SARS-CoV-2 pandemic was estimated in Wuhan, China, around November 24, 2019. Phylogenetic analyses of the first 12,511 SARS-CoV-2 whole genome sequences obtained worldwide, including 290 from 11 different regions of Spain, revealed 62 independent introductions of the virus in the country. Most sequences from Spain were distributed in clades characterized by D614G substitution in S gene (20A, 20B and 20C) and L84S substitution in ORF8 (19B) with 163 and 118 sequences, respectively, with the remaining sequences branching in 19A. A total of 110 (38%) sequences from Spain grouped in four different monophyletic clusters of 20A clade (20A-Sp1 and 20A-Sp2) and 19B clade (19B-Sp1 and 19B-Sp2) along with sequences from 29 countries worldwide. The MRCA of 19A-Sp1, 20A-Sp1, 19A-Sp2 and 20A-Sp2 clusters were estimated in Spain around January 21 and 29, and February 6 and 17, 2020, respectively. The prevalence of 19B clade in Spain (40%) was by far higher than in any other European country during the first weeks of the epidemic, probably by a founder effect. However, this variant was replaced by G614-bearing viruses in April. In vitro assays showed an enhanced infectivity of pseudotyped virions displaying G614 substitution compared with D614, suggesting a fitness advantage of D614G. IMPORTANCE Multiple SARS-CoV-2 introductions have been detected in Spain and at least four resulted in the emergence of locally transmitted clusters originated not later than mid-February, with further dissemination to many other countries around the world and a few weeks before the explosion of COVID-19 cases detected in Spain during the first week of March. The majority of the earliest variants detected in Spain branched in 19B clade (D614 viruses), which was the most prevalent clade during the first weeks of March, pointing to a founder effect. However, from mid-March to June, 2020, G614-bearing viruses (20A, 20B and 20C clades) overcame D614 variants in Spain, probably as a consequence of an evolutionary advantage of this substitution in the spike protein. A higher infectivity of G614-bearing viruses compared to D614 variants was detected, suggesting that this substitution in SARS-CoV-2 spike protein could be behind the variant shift observed in Spain.

scholarly journals Comprehensive annotations of the mutational spectra of SARS‐CoV‐2 spike protein: a fast and accurate pipeline

2020 ◽  
Author(s):  
Mohammad Shaminur Rahman ◽  
Mohammad Rafiul Islam ◽  
Mohammad Nazmul Hoque ◽  
Abu Sayed Mohammad Rubayet Ul Alam ◽  
Masuda Akther ◽  
...  
Keyword(s):  
Protein A ◽  
Spike Protein ◽  
Mutational Spectra

scholarly journals Low-Dose Fluvoxamine Modulates Endocytic Trafficking of SARS-CoV-2 Spike Protein: A Potential Mechanism for Anti-COVID-19 Protection by Antidepressants

2021 ◽  
Vol 12 ◽  
Author(s):  
Oleg O. Glebov
Keyword(s):  
Membrane Trafficking ◽  
Low Dose ◽  
Protein A ◽  
Antidepressant Drug ◽  
Fluid Phase ◽  
Spike Protein ◽  
Endosomal Trafficking ◽  
Therapeutic Concentration ◽  
Early Endosomes ◽  
Fluid Phase Endocytosis

Commonly prescribed antidepressants may be associated with protection against severe COVID-19. The mechanism of their action in this context, however, remains unknown. Here, I investigated the effect of an antidepressant drug fluvoxamine on membrane trafficking of the SARS-CoV-2 spike protein and its cell host receptor ACE2 in HEK293T cells. A sub-therapeutic concentration (80 nM) of fluvoxamine rapidly upregulated fluid-phase endocytosis, resulting in enhanced accumulation of the spike-ACE2 complex in enlarged early endosomes. Diversion of endosomal trafficking provides a simple cell biological mechanism consistent with the protective effect of antidepressants against COVID-19, highlighting their therapeutic and prophylactic potential.

scholarly journals Molecular rationale for SARS-CoV-2 spike circulating mutations able to escape bamlanivimab and etesevimab monoclonal antibodies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Erik Laurini ◽  
Domenico Marson ◽  
Suzana Aulic ◽  
Alice Fermeglia ◽  
Sabrina Pricl
Keyword(s):  
Monoclonal Antibodies ◽  
In Silico ◽  
Structural Information ◽  
Viral Evolution ◽  
Protein A ◽  
Immune Surveillance ◽  
Protein S ◽  
Spike Protein ◽  
Wild Type ◽  
Experimental Findings

AbstractThe purpose of this work is to provide an in silico molecular rationale of the role eventually played by currently circulating mutations in the receptor binding domain of the SARS-CoV-2 spike protein (S-RBDCoV‑2) in evading the immune surveillance effects elicited by the two Eli Lilly LY-CoV555/bamlanivimab and LY-CoV016/etesevimab monoclonal antibodies. The main findings from this study show that, compared to the wild-type SARS-CoV-2 spike protein, mutations E484A/G/K/Q/R/V, Q493K/L/R, S494A/P/R, L452R and F490S are predicted to be markedly resistant to neutralization by LY-CoV555, while mutations K417E/N/T, D420A/G/N, N460I/K/S/T, T415P, and Y489C/S are predicted to confer LY-CoV016 escaping advantage to the viral protein. A challenge of our global in silico results against relevant experimental data resulted in an overall 90% agreement. Thus, the results presented provide a molecular-based rationale for all relative experimental findings, constitute a fast and reliable tool for identifying and prioritizing all present and newly reported circulating spike SARS-CoV-2 variants with respect to antibody neutralization, and yield substantial structural information for the development of next-generation vaccines and monoclonal antibodies more resilient to viral evolution.

scholarly journals COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance

2021 ◽  
Author(s):  
Michele Simonetti ◽  
Ning Zhang ◽  
Luuk Harbers ◽  
Maria Grazia Milia ◽  
Thi Thu Huong Nguyen ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Protein A ◽  
Cost Effective ◽  
Mass Scale ◽  
Influenza Viruses ◽  
Spike Protein ◽  
Genome Coverage ◽  
Effective Manner ◽  
Geographical Regions ◽  
Different Populations

Abstract Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to monitor the spread and evolution of the virus across different populations, geographical regions and species. Here, we present a streamlined workflow—COVseq—based on the CUTseq method that we previously described, which can be used to generate highly multiplexed sequencing libraries compatible with Illumina platforms, from hundreds of SARS-CoV-2 samples in parallel, in a rapid and cost-effective manner. We validated COVseq on RNA extracted from the supernatant of a SARS-CoV-2 culture as well as from 85 left-over samples from nasopharyngeal swabs, demonstrating the ability of COVseq to achieve almost complete genome coverage, including the S region encoding the spike protein. A cost analysis showed that COVseq could be used to sequence thousands of samples per week at less than 20 USD per sample. COVseq is a versatile and scalable method that can be readily applied for genomic surveillance of the ongoing pandemic and easily adapted to other pathogens such as influenza viruses.

scholarly journals Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 673
Author(s):  
Riadh Badraoui ◽  
Mohd Adnan ◽  
Fevzi Bardakci ◽  
Mousa M. Alreshidi
Keyword(s):  
Molecular Docking ◽  
Computational Study ◽  
Management Strategies ◽  
Protein A ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Disease Pathogenesis ◽  
Docking Approach ◽  
Coding Variants ◽  
The Relationship

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inducing coronavirus disease 2019 (COVID-19) is still an ongoing challenge. To date, more than 95.4 million have been infected and more than two million deaths have been officially reported by the WHO. Angiotensin-converting enzyme (ACE) plays a key role in the disease pathogenesis. In this computational study, seventeen coding variants were found to be important for ACE2 binding with the coronavirus spike protein. The frequencies of these allele variants range from 3.88 × 10−3 to 5.47 × 10−6 for rs4646116 (K26R) and rs1238146879 (P426A), respectively. Chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are mainly used to prevent and treat malaria and rheumatic diseases. They are also used in several countries to treat SARS-CoV-2 infection inducing COVID-19. Both CQ and HCQ were found to interact differently with the various ACE2 domains reported to bind with coronavirus spike protein. A molecular docking approach revealed that intermolecular interactions of both CQ and HCQ exhibited mediation by ACE2 polymorphism. Further explorations of the relationship and the interactions between ACE2 polymorphism and CQ/HCQ would certainly help to better understand the COVID-19 management strategies, particularly their use in the absence of specific vaccines or drugs.

scholarly journals COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance

2021 ◽  
Author(s):  
Michele Simonetti ◽  
Ning Zhang ◽  
Luuk Harbers ◽  
Maria Grazia Milia ◽  
Thi Nguyen ◽  
...  
Keyword(s):  
Protein A ◽  
Cost Effective ◽  
Mass Scale ◽  
Influenza Viruses ◽  
Spike Protein ◽  
Library Preparation ◽  
Genome Coverage ◽  
Effective Manner ◽  
Geographical Regions ◽  
Different Populations

Abstract Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to monitor the spread and evolution of the virus across different populations, geographical regions and species. Here, we present a streamlined workflow—COVseq—based on the CUTseq method that we previously described, which can be used to generate highly multiplexed sequencing libraries compatible with Illumina platforms, from hundreds of SARS-CoV-2 samples in parallel, in a rapid and cost-effective manner. We validated COVseq on RNA extracted from the supernatant of a SARS-CoV-2 culture as well as from 85 RNA samples from nasopharyngeal swabs, demonstrating the ability of COVseq to achieve near complete genome coverage, including the S region encoding the spike protein. A cost analysis showed that COVseq could be used to sequence thousands of samples per week at less than 10 USD per sample, including library preparation and sequencing costs. COVseq is a versatile and scalable method that can be readily applied for genomic surveillance of the ongoing pandemic and easily adapted to other pathogens such as influenza viruses.

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