SARS-CoV-2 membrane protein: from genomic data to structural new insights

Abstract Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) is composed by four structural proteins and several accessory non-structural proteins. SARS-CoV-2's most abundant structural protein, Membrane (M) protein, has a pivotal role both during viral infection cycle and host interferon antagonism. This is a highly conserved viral protein, thus an interesting and suitable target for drug discovery.In this paper, we explain the structural and dynamic nature of M protein homodimer. To do so, we developed and applied a detailed and robust in silico workflow to predict M protein dimeric structure, membrane orientation, and interface characterization. Single Nucleotide Polymorphisms (SNPs) in M protein were retrieved from over 1.2 M SARS-CoV-2 genomes and proteins from the Global Initiative on Sharing All Influenza Data (GISAID) database, 91 of which were located at the predicted dimer interface. Among those, we identified SNPs in Variants of Concern (VOC) and Variants of Interest (VOI). Binding free energy differences were evaluated for dimer interfacial SNPs to infer mutant protein stabilities. A few high-prevalent mutated residues were found to be especially relevant in VOC and VOI. This realization may be a game changer to structure driven formulation of new therapeutics for SARS-CoV-2.

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Nuclear receptors in disease: the oestrogen receptors

Essays in Biochemistry ◽

10.1042/bse0400157 ◽

2004 ◽

Vol 40 ◽

pp. 157-167 ◽

Cited By ~ 18

Author(s):

Maria Nilsson ◽

Karin Dahlman-Wright ◽

Jan-Åke Gustafsson

Keyword(s):

Nuclear Receptors ◽

Target Genes ◽

Receptor Subtype ◽

Target Tissue ◽

Oestrogen Receptors ◽

Nucleotide Polymorphisms ◽

Cell Type ◽

Single Nucleotide ◽

Beneficial Effects ◽

The Family

For several decades, it has been known that oestrogens are essential for human health. The discovery that there are two oestrogen receptors (ERs), ERalpha and ERbeta, has facilitated our understanding of how the hormone exerts its physiological effects. The ERs belong to the family of ligand-activated nuclear receptors, which act by modulating the expression of target genes. Studies of ER-knockout (ERKO) mice have been instrumental in defining the relevance of a given receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest diseases in which dysfunctional ERs might be involved in aetiology and pathology. Association between single-nucleotide polymorphisms (SNPs) in ER genes and disease have been demonstrated in several cases. Selective ER modulators (SERMs), which are selective with regard to their effects in a certain cell type, already exist. Since oestrogen has effects in many tissues, the goal with a SERM is to provide beneficial effects in one target tissue while avoiding side effects in others. Refined SERMs will, in the future, provide improved therapeutic strategies for existing and novel indications.

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Development of a simple method for the determination of single nucleotide polymorphisms

Cell Biology International ◽

10.1042/cbi034s075c ◽

2010 ◽

Vol 34 (8) ◽

pp. S75-S75

Author(s):

Weifeng Zhu ◽

Zhuoqi Liu ◽

Daya Luo ◽

Xinyao Wu ◽

Fusheng Wan

Keyword(s):

Single Nucleotide Polymorphisms ◽

Nucleotide Polymorphisms ◽

Simple Method ◽

Single Nucleotide

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Single nucleotide polymorphisms in intron 5 of the feline myosin regulatory light chain gene detected by SSCP analysis

Animal Genetics ◽

10.1046/j.1365-2052.2000.00620.x ◽

2000 ◽

Vol 31 (4) ◽

pp. 281-282

Author(s):

A L Magnon ◽

K M Meurs ◽

M D Kittleson ◽

W A Ware

Keyword(s):

Single Nucleotide Polymorphisms ◽

Light Chain ◽

Regulatory Light Chain ◽

Sscp Analysis ◽

Chain Gene ◽

Myosin Regulatory Light Chain ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Light Chain Gene

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Single nucleotide polymorphisms of the factor IX gene for linkage analysis in the southern Chinese population

British Journal of Haematology ◽

10.1046/j.1365-2141.2000.02384.x ◽

2000 ◽

Vol 111 (2) ◽

pp. 540-543 ◽

Cited By ~ 2

Author(s):

Vivian Chan ◽

Irene Yam ◽

B. Yip ◽

P. Au ◽

M. K. Shing ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Linkage Analysis ◽

Chinese Population ◽

Factor Ix ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Southern Chinese

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W14.373 A single nucleotide polymorphisms of the apolipoprotein A-V gene (SNP3, T-1131C) modulates postprandial lipoprotein metabolism

Atherosclerosis ◽

10.1016/s0021-9150(04)90372-3 ◽

2004 ◽

Vol 5 (1) ◽

pp. 86

Author(s):

C MARIN

Keyword(s):

Single Nucleotide Polymorphisms ◽

Lipoprotein Metabolism ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Apolipoprotein A ◽

V Gene ◽

Postprandial Lipoprotein

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Sex Differences in Childhood Associations between DNA Markers and General Cognitive Ability

Journal of Individual Differences ◽

10.1027/1614-0001.28.3.161 ◽

2007 ◽

Vol 28 (3) ◽

pp. 161-164 ◽

Cited By ~ 1

Author(s):

Rosalind Arden ◽

Nicole Harlaar ◽

Robert Plomin

Keyword(s):

Sex Differences ◽

Single Nucleotide Polymorphisms ◽

Cognitive Ability ◽

Dna Markers ◽

Community Sample ◽

Nucleotide Polymorphisms ◽

General Cognitive Ability ◽

Single Nucleotide ◽

The Difference

Abstract. An association between intelligence at age 7 and a set of five single-nucleotide polymorphisms (SNPs) has been identified and replicated. We used this composite SNP set to investigate whether the associations differ between boys and girls for general cognitive ability at ages 2, 3, 4, 7, 9, and 10 years. In a longitudinal community sample of British twins aged 2-10 (n > 4,000 individuals), we found that the SNP set is more strongly associated with intelligence in males than in females at ages 7, 9, and 10 and the difference is significant at 10. If this finding replicates in other studies, these results will constitute the first evidence of the same autosomal genes acting differently on intelligence in the two sexes.

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