Anti‐SARS‐CoV‐2 activity of targeted kinase inhibitors: Repurposing clinically available drugs for COVID‐19 therapy DOI
RuthMabel Boytz, Mikołaj Słabicki, Sita Ramaswamy

et al.

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 95(1)

Published: Sept. 19, 2022

Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle symptoms infection. Repurposing kinase inhibitors is appealing as they have been vetted safety are more accessible COVID-19 treatment. However, an understanding mechanism needed to improve our factors involved in pathogenesis. We tested vitro activity three against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including AXL kinase, host cell factor that contributes successful SARS-CoV-2 Using multiple cell-based assays approaches, gilteritinib, nintedanib, imatinib were thoroughly evaluated variants. Each exhibited activity, but stark differences potency, suggesting dependency targets. Importantly, amount compound achieve 90% infection inhibition, at least part involving blockade spike protein-mediated entry concentrations not inducing phospholipidosis (PLD), approached clinically achievable concentration. Knockout AXL, gilteritinib impaired variant infectivity, supporting role further investigation drug-mediated inhibition This study supports evaluation AXL-targeting potential agents treatments COVID-19. Additional mechanistic studies determine underlying virus response.

Language: Английский

Molecular basis of receptor binding and antibody neutralization of Omicron DOI Open Access
Hong Qin, Wenyu Han, Jiawei Li

et al.

Nature, Journal Year: 2022, Volume and Issue: 604(7906), P. 546 - 552

Published: Feb. 28, 2022

Language: Английский

Citations

189
SARS-CoV-2 Mutations and their Viral Variants DOI Open Access
Begüm Coşar, Zeynep Yağmur KARAGÜLLEOĞLU, Sinan ÜNAL

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2021, Volume and Issue: 63, P. 10 - 22

Published: July 2, 2021

Language: Английский

Citations

181
Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies DOI Creative Commons
Yifan Wang, Caixuan Liu, Chao Zhang

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 15, 2022

Abstract The SARS-CoV-2 Delta variant is currently the dominant circulating strain in world. Uncovering structural basis of enhanced transmission and altered immune sensitivity particularly important. Here we present cryo-EM structures revealing two conformational states spike S/ACE2 complex four states. Our analysis suggests that RBD destabilizations lead to population shift towards more RBD-up S1 destabilized fusion-prone state, beneficial for engagement with ACE2 shedding S1. Noteworthy, find T478K substitution plays a vital role stabilizing reshaping RBM loop 473-490 , enhancing interaction ACE2. Collectively, increased propensity affinity-enhancing together contribute binding, providing rapid spread Delta. Moreover, identify previously generated MAb 8D3 as cross-variant broadly neutralizing antibody reveal binding induces large K478 side-chain orientation change, suggesting may use an “induced-fit” mechanism tolerate mutation. We also all five RBD-targeting MAbs tested remain effective on Delta, well preserves antigenic landscape RBD. findings shed new lights pathogenicity neutralization

Language: Английский

Citations

158
From delta to Omicron: S1-RBD/S2 mutation/deletion equilibrium in SARS-CoV-2 defined variants DOI
Vasileios Papanikolaou, Aristeidis Chrysovergis, Vasileios Ragos

et al.

Gene, Journal Year: 2022, Volume and Issue: 814, P. 146134 - 146134

Published: Jan. 4, 2022

Language: Английский

Citations

138
Advances in the Omicron variant development DOI Open Access
Antonio Vitiello, Francesco Ferrara, Amogh Auti

et al.

Journal of Internal Medicine, Journal Year: 2022, Volume and Issue: 292(1), P. 81 - 90

Published: March 15, 2022

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread worldwide, leading the World Health Organization (WHO) to declare a pandemic, on 11 March 2020. Variants of concern have appeared at regular intervals-Alpha, Beta, Gamma, Delta, and now Omicron. Omicron variant, first identified in Botswana November 2021, is rapidly becoming dominant circulating variant. In this review, we provide an overview regarding molecular profile epidemiology, transmissibility, impact vaccines, as well vaccine escape, finally, report pharmacological agents able block endocellular entry SARS-CoV-2 or inhibit its viral replication. The more than 50 mutations, which spike protein 26-35 amino acids different from original virus some are associated with humoral immune escape potential greater transmissibility. significant growth advantage over rapid higher incidence levels. disease so far been mild compared Delta. two vaccination doses offer little no protection against infection while booster illness likely even levels serious illness. Recently, new oral antiviral such molnupiravir paxlovid approved represent important therapeutic alternatives remdesivir. addition, monoclonal antibodies casirivimab/imdevimab bind epitopes receptor; class drugs effective variant? However, research needed define whether indeed infectious antibodies, antivirals currently available effective.

Language: Английский

Citations

136
Emerging SARS-CoV-2 Variants of Concern (VOCs): An Impending Global Crisis DOI Creative Commons

Angel Yun-Kuan Thye,

Jodi Woan‐Fei Law, Priyia Pusparajah

et al.

Biomedicines, Journal Year: 2021, Volume and Issue: 9(10), P. 1303 - 1303

Published: Sept. 23, 2021

The worldwide battle against the SARS-CoV-2 virus rages on, with millions infected and many innocent lives lost. causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a beta that belongs to Coronaviridae family. Many clinically significant variants have emerged, as virus’s genome prone various mutations, leading antigenic drift resulting in evasion of host immune recognition. current concern (VOCs) include B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617/B.1.617.2 (Delta), P.1 (Gamma). emerging contain important mutations on spike protein, deleterious consequences, such invasion vaccine escape. These adverse effects result increased transmissibility, morbidity, mortality detection by existing or currently available diagnostic tests, potentially delaying diagnosis treatment. This review discusses key present VOC strains provides insights into how these allow for greater transmissibility than progenitor strain. Continuous monitoring surveillance play vital role preventing controlling spread.

Language: Английский

Citations

122
SARS‐CoV‐2 variants and vulnerability at the global level DOI Creative Commons
Vivek P. Chavda, Aayushi Patel, Darsh D. Vaghasiya

et al.

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(7), P. 2986 - 3005

Published: March 12, 2022

Numerous variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have evolved. Viral may evolve with harmful susceptibility to immunity established existing COVID-19 vaccination. These are more transmissible, induce relatively extreme illness, evasive immunological features, decrease neutralization using antibodies from vaccinated persons, and susceptible re-infection. The Centers for Disease Control Prevention (CDC) has categorized SARS-CoV-2 mutations as interest (VOI), concern (VOC), high consequence (VOHC). At moment, four VOC many been defined require constant observation. This review article summarizes various surfaced special emphasis on VOCs that spreading across world, well several viral mutational impacts how these modifications alter properties virus.

Language: Английский

Citations

111
From Alpha to Omicron: How Different Variants of Concern of the SARS-Coronavirus-2 Impacted the World DOI Creative Commons

Mickensone Andre,

Lee-Seng Lau,

Marissa D. Pokharel

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(9), P. 1267 - 1267

Published: Sept. 21, 2023

SARS-CoV-2, the virus that causes COVID-19, is prone to mutations and generation of genetic variants. Since its first outbreak in 2019, SARS-CoV-2 has continually evolved, resulting emergence several lineages variants concern (VOC) have gained more efficient transmission, severity, immune evasion properties. The World Health Organization given these names according letters Greek Alphabet, starting with Alpha (B.1.1.7) variant, which emerged 2020, followed by Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron (B.1.1.529) This review explores variation among different VOCs how made a global impact on pandemic.

Language: Английский

Citations

55
An overview of the vaccine platforms to combat COVID-19 with a focus on the subunit vaccines DOI Open Access
Fatemeh Bayani,

Negin Safaei Hashkavaei,

Sareh Arjmand

et al.

Progress in Biophysics and Molecular Biology, Journal Year: 2023, Volume and Issue: 178, P. 32 - 49

Published: Feb. 20, 2023

Language: Английский

Citations

49
Possible Link between Higher Transmissibility of Alpha, Kappa and Delta Variants of SARS-CoV-2 and Increased Structural Stability of Its Spike Protein and hACE2 Affinity DOI Open Access
Vipul Kumar, Jasdeep Singh, Seyed E. Hasnain

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(17), P. 9131 - 9131

Published: Aug. 24, 2021

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak in December 2019 has caused a global pandemic. rapid mutation rate the virus created alarming situations worldwide and is being attributed to false negativity RT-PCR tests. It also increased chances of reinfection immune escape. Recently various lineages namely, B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta) B.1.617.3 have infection around globe. To understand biophysical perspective, we performed molecular dynamic simulations four different spikes (receptor binding domain)-hACE2 complexes, namely wildtype (WT), Alpha variant (N501Y spike mutant), Kappa (L452R, E484Q) Delta T478K), compared their dynamics, energy interactions. Our results show that significant increase between hACE2 variants. In case variants, mutations at L452R, T478K E484Q stability intra-chain interactions protein, which may change interaction ability neutralizing antibodies these Further, found had hydrogen with Lys353 more affinity comparison WT. current study provides basis for understanding mechanism rationale behind transmissivity infectivity mutants wild-type SARS-CoV-2.

Language: Английский

Citations

84