Emergence of SARS-COV-2 Spike Protein Escape Mutation Q493R after Treatment for COVID-19

Rapid emergence of SARS-CoV-2 variants is a constant threat and a major hurdle to reach heard immunity. We produced VBI-2905a, an enveloped virus-like particules (eVLP)-based vaccine candidate expressing prefusion spike protein from the Beta variant that contains several escape mutation. VBI-2905a protected hamsters against infection with a Beta variant virus and induced high levels of neutralizing antibodies against Beta RBD. In a heterologous vaccination regimen, a single injection of VBI-2905a in animals previously immunized with VBI-2902, a vaccine candidate expressing S from ancestral SARS-CoV-2, hamsters were equally protected against Beta variant infection. As an alternate strategy to broaden immunity, we produced a trivalent vaccine expressing the prefusion spike protein from SARS-CoV-2 together with unmodifed S from SARS-CoV-1 and MERS-CoV. Relative to immunity induced against the ancestral strain, the trivalent vaccine VBI-2901a induced higher and more consistent antibody binding and neutralizing responses against a panel of variants including Beta, Delta, Kappa, and Lambda, with evidence for broadening of immunity rather than just boosting cross-reactivity antibodies.

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Coding-Complete Genome Sequences and Mutation Profiles of Nine SARS-CoV-2 Strains Detected from COVID-19 Patients in Bangladesh

Microbiology Resource Announcements ◽

10.1128/mra.00124-21 ◽

2021 ◽

Vol 10 (10) ◽

Author(s):

Nihad Adnan ◽

Mohib Ullah Khondoker ◽

M. Shaminur Rahman ◽

M. Firoz Ahmed ◽

Shahana Sharmin ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Complete Genome ◽

Spike Protein ◽

Escape Mutation ◽

Coding Region ◽

Genome Sequences ◽

Protein Coding

ABSTRACT Here, we report the coding-complete genome sequences of nine clinical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and their mutations. The samples were collected from nine Bangladeshi coronavirus disease 2019 (COVID-19) patients. We have identified the E484K escape mutation and the S359T mutation within the spike protein coding region of the sequenced genomes.

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First antibody against COVID-19 spike protein enters phase I

Nature Reviews Drug Discovery ◽

10.1038/d41573-020-00108-x ◽

2020 ◽

Vol 19 (7) ◽

pp. 435-435

Author(s):

Asher Mullard

Keyword(s):

Phase I ◽

Spike Protein

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Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

10.26434/chemrxiv.12186624.v3 ◽

2020 ◽

Author(s):

Cristina Garcia-Iriepa ◽

Cecilia Hognon ◽

Antonio Francés-Monerris ◽

Isabel Iriepa ◽

Tom Miclot ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Molecular Mechanisms ◽

Molecular Design ◽

Binding Free Energy ◽

Transmembrane Protein ◽

Spike Protein ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Rational Molecular Design ◽

Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

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Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

10.31222/osf.io/78mbt ◽

2020 ◽

Author(s):

Sanaa Bardaweel

Keyword(s):

Clinical Trials ◽

Drug Discovery ◽

Antimalarial Drug ◽

Drug Repurposing ◽

Spike Protein ◽

Diabetic Patients ◽

Potential Drug ◽

Chemokine Production ◽

Drug Discovery And Development ◽

Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

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