Proteo-Genomic Analysis of SARS-CoV-2: A Clinical Landscape of Single-Nucleotide Polymorphisms, COVID-19 Proteome, and Host Responses

Tushir, Sheetal; Kamanna, Sathisha; Nath, Sujith S; Bhat, Aishwarya; Rose, Steffimol; Aithal, Advait R; Tatu, Utpal

doi:10.1021/acs.jproteome.0c00808

Cited by 14 publications

(11 citation statements)

References 43 publications

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“…An average of ≥11 mutations per sample with the insurgence of single nucleotide substitutions was reported for SARS-CoV-2 [8,20]. These mutations are categorized as amino acid changing SNP (single nucleotide polymorphism), amino acid changing triplet, 5'UTR-SNP and silent SNP.…”

Section: Predominant Mutation Clusters In Sars-cov-2 Genomementioning

confidence: 99%

SARS-CoV-2 mutations: the biological trackway towards viral fitness

Majumdar¹,

Niyogi²

2021

Epidemiol. Infect.

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The outbreak of pneumonia-like respiratory disorder at China and its rapid transmission world-wide resulted in public health emergency, which brought lineage B betacoronaviridae SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) into spotlight. The fairly high mutation rate, frequent recombination and interspecies transmission in betacoronaviridae are largely responsible for their temporal changes in infectivity and virulence. Investigation of global SARS-CoV-2 genotypes revealed considerable mutations in structural, non-structural, accessory proteins as well as untranslated regions. Among the various types of mutations, single-nucleotide substitutions are the predominant ones. In addition, insertion, deletion and frame-shift mutations are also reported, albeit at a lower frequency. Among the structural proteins, spike glycoprotein and nucleocapsid phosphoprotein accumulated a larger number of mutations whereas envelope and membrane proteins are mostly conserved. Spike protein and RNA-dependent RNA polymerase variants, D614G and P323L in combination became dominant world-wide. Divergent genetic variants created serious challenge towards the development of therapeutics and vaccines. This review will consolidate mutations in different SARS-CoV-2 proteins and their implications on viral fitness.

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Section: Predominant Mutation Clusters In Sars-cov-2 Genomementioning

confidence: 99%

SARS-CoV-2 mutations: the biological trackway towards viral fitness

Majumdar¹,

Niyogi²

2021

Epidemiol. Infect.

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“…The time course of changes in mechanics has been well-illustrated by (29). Alternatively, these differences might be related to the different lineages of coronavirus (36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Positive End-Expiratory Pressure Strategies in Patients With Coronavirus Disease 2019–Induced Acute Respiratory Distress Syndrome

et al. 2021

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Background: Different positive end-expiratory pressure (PEEP) strategies are available for subjects with coronavirus disease 2019 (COVID-19)–induced acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. We aimed to evaluate three conventional PEEP strategies on their effects on respiratory mechanics, gas exchanges, and hemodynamics.Methods: This is a prospective, physiologic, multicenter study conducted in China. We recruited 20 intubated subjects with ARDS and confirmed COVID-19. We first set PEEP by the ARDSnet low PEEP–fraction of inspired oxygen (FIO2) table. After a recruitment maneuver, PEEP was set at 15, 10, and 5 cm H2O for 10 min, respectively. Among these three PEEP levels, best-compliance PEEP was the one providing the highest respiratory system compliance; best-oxygenation PEEP was the one providing the highest PaO2 (partial pressure of arterial oxygen)/FIO2.Results: At each PEEP level, we assessed respiratory mechanics, arterial blood gas, and hemodynamics. Among three PEEP levels, plateau pressure, driving pressure, mechanical power, and blood pressure improved with lower PEEP. The ARDSnet low PEEP–FIO2 table and the best-oxygenation strategies provided higher PEEP than the best-compliance strategy (11 ± 6 cm H2O vs. 11 ± 3 cm H2O vs. 6 ± 2 cm H2O, p = 0.001), leading to higher plateau pressure, driving pressure, and mechanical power. The three PEEP strategies were not significantly different in gas exchange. The subgroup analysis showed that three PEEP strategies generated different effects in subjects with moderate or severe ARDS (n = 12) but not in subjects with mild ARDS (n = 8).Conclusions: In our cohort with COVID-19–induced ARDS, the ARDSnet low PEEP/FIO2 table and the best-oxygenation strategies led to higher PEEP and potentially higher risk of ventilator-induced lung injury than the best-compliance strategy.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04359251.

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“…The majority of drugs used for SARS-CoV-2 treatment are drugs currently in use for treatment of other diseases [243][244][245], and these have been evaluated for their efficacy using computational drug discovery analysis [246][247][248]. Although NGS has been used primarily for genome identification of SARS-CoV-2 [249][250][251][252], as well as for evaluation of mutations developed during viral spread in different countries [253][254][255], there are some studies wherein RNA sequencing is used for identifying new drug treatments. One such study has used NGS for evaluation of affected genes during SARS-CoV-2 infections.…”

Section: Ngs In Sars-cov-2 Drug Discoverymentioning

confidence: 99%

Microarrays and NGS for Drug Discovery

Pop¹,

Zănoagă²,

Chiroi³

et al. 2021

Drug Design - Novel Advances in the Omics Field and Applications

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Novel technologies and state of the art platforms developed and launched over the last two decades such as microarrays, next-generation sequencing, and droplet PCR have provided the medical field many opportunities to generate and analyze big data from the human genome, particularly of genomes altered by different diseases like cancer, cardiovascular, diabetes and obesity. This knowledge further serves for either new drug discovery or drug repositioning. Designing drugs for specific mutations and genotypes will dramatically modify a patient’s response to treatment. Among other altered mechanisms, drug resistance is of concern, particularly when there is no response to cancer therapy. Once these new platforms for omics data are in place, available information will be used to pursue precision medicine and to establish new therapeutic guidelines. Target identification for new drugs is necessary, and it is of great benefit for critical cases where no alternatives are available. While mutational status is of highest importance as some mutations can be pathogenic, screening of known compounds in different preclinical models offer new and quick strategies to find alternative frameworks for treating more diseases with limited therapeutic options.

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Proteo-Genomic Analysis of SARS-CoV-2: A Clinical Landscape of Single-Nucleotide Polymorphisms, COVID-19 Proteome, and Host Responses

Cited by 14 publications

References 43 publications

SARS-CoV-2 mutations: the biological trackway towards viral fitness

SARS-CoV-2 mutations: the biological trackway towards viral fitness

Evaluation of Positive End-Expiratory Pressure Strategies in Patients With Coronavirus Disease 2019–Induced Acute Respiratory Distress Syndrome

Microarrays and NGS for Drug Discovery

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