Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19

Cells, Journal Year: 2021, Volume and Issue: 10(4), P. 821 - 821

Published: April 6, 2021

Coronavirus belongs to the family of Coronaviridae, comprising single-stranded, positive-sense RNA genome (+ ssRNA) around 26 32 kilobases, and has been known cause infection a myriad mammalian hosts, such as humans, cats, bats, civets, dogs, camels with varied consequences in terms death debilitation. Strikingly, novel coronavirus (2019-nCoV), later renamed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), found be causative agent disease-19 (COVID-19), shows 88% sequence identity bat-SL-CoVZC45 bat-SL-CoVZXC21, 79% SARS-CoV 50% MERS-CoV, respectively. Despite key amino acid residual variability, there is an incredible structural similarity between receptor binding domain (RBD) spike protein (S) SARS-CoV-2 SARS-CoV. During infection, compared displays 10–20 times greater affinity for its cognate host cell receptor, angiotensin-converting enzyme 2 (ACE2), leading proteolytic cleavage S by transmembrane protease serine (TMPRSS2). Following cellular entry, ORF-1a ORF-1ab, located downstream 5′ end + ssRNA genome, undergo translation, thereby forming two large polyproteins, pp1a pp1ab. These following protease-induced molecular assembly, form functional viral polymerase, also referred replicase. Thereafter, uninterrupted orchestrated replication-transcription events lead synthesis multiple nested sets subgenomic mRNAs (sgRNAs), which are finally translated several accessory proteins participating structure formation various functions virus, assemble encapsulate genomic (gRNA), resulting numerous progenies, eventually exit cell, spread rest body. In this review, we primarily focus on organization, non-structural components, potential prospective targets development therapeutic drugs, convalescent plasm therapy, vaccines tackle infection.

Language: Английский

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Immune Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far?

Viruses, Journal Year: 2021, Volume and Issue: 13(7), P. 1192 - 1192

Published: June 22, 2021

Despite the slow evolutionary rate of SARS-CoV-2 relative to other RNA viruses, its massive and rapid transmission during COVID-19 pandemic has enabled it acquire significant genetic diversity since first entered human population. This led emergence numerous variants, some them recently being labeled “variants concern” (VOC), due their potential impact on transmission, morbidity/mortality, evasion neutralization by antibodies elicited infection, vaccination, or therapeutic application. The evade is result target epitopes generated accumulation mutations in spike protein. While three globally recognized VOCs (Alpha B.1.1.7, Beta B.1.351, Gamma P.1) remain sensitive albeit at reduced levels sera convalescent individuals recipients several anti-COVID19 vaccines, effect variability much more evident capacity monoclonal antibodies. newly VOC Delta lineage B.1.617.2, as well locally accepted (Epsilon B.1.427/29-US B1.1.7 with E484K-UK) are indicating necessity close monitoring new variants a global level. characteristics, mutational patterns, role play immune summarized this review.

Language: Английский

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Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe

Infection, Journal Year: 2021, Volume and Issue: 50(2), P. 309 - 325

Published: Dec. 16, 2021

Language: Английский

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Structure-Function Analyses of New SARS-CoV-2 Variants B.1.1.7, B.1.351 and B.1.1.28.1: Clinical, Diagnostic, Therapeutic and Public Health Implications

Viruses, Journal Year: 2021, Volume and Issue: 13(3), P. 439 - 439

Published: March 9, 2021

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) has accumulated multiple mutations during its global circulation. Recently, three lineages, B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1), have emerged in the United Kingdom, South Africa Brazil, respectively. Here, we presented viewpoint on implications of emerging variants based structural–function impact crucial occurring spike (S), ORF8 nucleocapsid (N) proteins. While N501Y mutation was observed all 501Y.V1 P.1 a different set S protein. The missense mutational effects were predicted through COVID-19 dedicated resource followed by atomistic molecular dynamics simulations. Current findings indicate that some protein might lead to higher affinity with host receptors resistance against antibodies, but not are due antibody binding (epitope) regions. Mutations may, however, result diagnostic tests failures possible interference newly identified anti-viral candidates SARS-CoV-2, likely necessitating roll out recurring “flu-like shots” annually for tackling COVID-19. functional relevance these been described terms modulation tropism, resistance, sensitivity therapeutic candidates. Besides economic losses, post-vaccine reinfections can significant clinical, public health impacts.

Language: Английский

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One Year of SARS-CoV-2: How Much Has the Virus Changed?

Biology, Journal Year: 2021, Volume and Issue: 10(2), P. 91 - 91

Published: Jan. 26, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide crisis with profound effects on both public health and the economy. In order to combat COVID-19 pandemic, research groups have shared viral genome sequence data through Global Initiative Sharing All Influenza Data (GISAID). Over past year, ≈290,000 full SARS-CoV-2 proteome sequences been deposited in GISAID. Here, we used these assess rate of nonsynonymous mutants over entire proteome. Our analysis shows that proteins are mutating at substantially different rates, most exhibiting little mutational variability. As anticipated, our calculations capture previously reported mutations arose first months such as D614G (Spike), P323L (NSP12), R203K/G204R (Nucleocapsid), but they also identify more recent mutations, A222V L18F (Spike) A220V among others. comprehensive temporal geographical analyses show two distinct periods mutation rates: December 2019 July 2020 August 2020. Notably, some rates differ by geography, primarily during latter half Europe. Furthermore, structure-based molecular provides an exhaustive assessment context current set 3D structures available for proteins. This emerging sequence-to-structure insight is beginning illuminate site-specific (in)tolerance virus continues spread around globe.

Language: Английский

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Structure genomics of SARS-CoV-2 and its Omicron variant: drug design templates for COVID-19

Acta Pharmacologica Sinica, Journal Year: 2022, Volume and Issue: 43(12), P. 3021 - 3033

Published: Jan. 20, 2022

Language: Английский

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An Effective MM/GBSA Protocol for Absolute Binding Free Energy Calculations: A Case Study on SARS-CoV-2 Spike Protein and the Human ACE2 Receptor

Molecules, Journal Year: 2021, Volume and Issue: 26(8), P. 2383 - 2383

Published: April 20, 2021

The binding free energy calculation of protein-ligand complexes is necessary for research into virus-host interactions and the relevant applications in drug discovery. However, many current computational methods such calculations are either inefficient or inaccurate practice. Utilizing implicit solvent models molecular mechanics generalized Born surface area (MM/GBSA) framework allows efficient without significant loss accuracy. Here, GBNSR6, a new flavor model, employed MM/GBSA measuring affinity between SARS-CoV-2 spike protein human ACE2 receptor. A protocol developed based on widely studied Ras-Raf complex, which has similar to SARS-CoV-2/ACE2. Two options representing dielectric boundary evaluated: one standard Bondi radii other newly set atomic (OPT1), optimized specifically binding. Predictions two sets provide upper lower bounds experimental references: -14.7(ΔGbindBondi)<-10.6(ΔGbindExp.)<-4.1(ΔGbindOPT1) kcal/mol. consensus estimates show quantitative agreement with experiment values. This work also presents novel truncation method strategies entropy normal mode analysis. Interestingly, it observed that decrease number snapshots does not affect accuracy calculation, while computation time appreciably. proposed can be used study mechanism variants SARS-CoV-2, as well structures.

Language: Английский

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The COVID-19 Vaccines: Recent Development, Challenges and Prospects

Vaccines, Journal Year: 2021, Volume and Issue: 9(4), P. 349 - 349

Published: April 5, 2021

The highly infectious coronavirus disease 2019 (COVID-19) associated with the pathogenic severe acute respiratory syndrome 2 (SARS-CoV-2) has spread to become a global pandemic. At present, world is relying mainly on containment and hygiene-related measures, as well repurposed drugs control outbreak. development of COVID-19 vaccines crucial for return pre-pandemic normalcy, collective effort been invested into protection against SARS-CoV-2. As March 2021, thirteen have approved application whilst over 90 vaccine candidates are under clinical trials. This review focuses highlights efficacy vaccination reactions authorised vaccines. mechanisms, storage, dosage specification at advanced stage also critically reviewed together considerations potential challenges. Whilst is, in general, its infancy, current progress promising. However, population will continue adapt “new normal” practice social distancing hygienic least until effective available general public.

Language: Английский

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Beneficial Properties of Bromelain

Nutrients, Journal Year: 2021, Volume and Issue: 13(12), P. 4313 - 4313

Published: Nov. 29, 2021

Bromelain is a major sulfhydryl proteolytic enzyme found in pineapple plants, having multiple activities many areas of medicine. Due to its low toxicity, high efficiency, availability, and relative simplicity acquisition, it the object inexhaustible interest scientists. This review summarizes scientific reports concerning possible application bromelain treating cardiovascular diseases, blood coagulation fibrinolysis disorders, infectious inflammation-associated types cancer. However, for proper such multi-action bromelain, further exploration mechanism action needed. It supposed that anti-viral, anti-inflammatory, cardioprotective anti-coagulatory activity may become complementary therapy COVID-19 post-COVID-19 patients. During irrepressible spread novel variants SARS-CoV-2 virus, beneficial properties this biomolecule might help prevent escalation progression disease.

Language: Английский

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TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein

Viruses, Journal Year: 2021, Volume and Issue: 13(3), P. 384 - 384

Published: Feb. 28, 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein facilitate cellular entry. Although TMPRSS2 is well-characterized type II protease (TTSP), role of other TTSPs on replication SARS-CoV-2 remains be elucidated. Here, we have screened 12 using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells Vero E6 demonstrated that exogenous expression TMPRSS11D TMPRSS13 enhanced uptake subsequent SARS-CoV-2. In addition, SARS-CoV-1 share same in viral entry process. Our study demonstrates impact infection SARS-CoV-2, which may implications for cell tissue tropism, pathogenicity, potentially vaccine development.

Language: Английский

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