The global coronavirus disease 2019 (COVID‐19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has led to an unprecedented worldwide public health emergency. Despite the concerted efforts of the scientific field, by April 25, 2021, SARS‐CoV‐2 had spread to over 192 countries/regions, causing more than 146 million confirmed cases including 31 million deaths. For now, an established treatment for patients with COVID‐19 remains unavailable. The key to tackling this pandemic is to understand the mechanisms underlying its infectivity and pathogenicity. As a predominant focus, the coronavirus spike (S) protein is the key determinant of host range, infectivity, and pathogenesis. Thereby comprehensive understanding of the sophisticated structure of SARS‐CoV‐2 S protein may provide insights into possible intervention strategies to fight this ongoing global pandemic. Herein, we summarize the current knowledge of the molecular structural and functional features of SARS‐CoV‐2 S protein as well as recent updates on the cell entry mechanism of the SARS‐CoV‐2, paving the way for exploring more structure‐guided strategies against SARS‐CoV‐2.

Background: Retinitis pigmentosa (RP) is the most common type of inherited retinopathy with at least 69 genes identified thus far. A significant proportion of RP, However, remains genetically unsolved. In this study, the the genetic basis of a Chinese consanguineous family with autosomal recessive retinitis pigmentosa (arRP) was investigated. Methods : Overall ophthalmic examinations, including funduscopy, decimal best-corrected visual acuity (BCVA), axial length and electroretinography (ERG) were performed to confirm the diagnosis of the patients. Genomic DNA from peripheral blood of the proband was subjected to whole exome sequencing (WES). In silico predictions, structural modelling and minigene assays were conducted to evaluate the pathogenicity of the mutant. Results : Four candidate variants, including heterozygous variant in RAX2, RP1 and PITPNM3 and a homozygous variant in Tub , were detected as suspected pathegenic variants. The novel c.1379A > G mutation in Tub , based on sanger sequencing, was remained to be the only candidate variant that co-segregated with RP phenotype in this pedigree. More importantly, the Asn residue at codon 460 of TUB is highly conserved across diverse species from tropicalis to humans. And the homozygous c.1379A > G mutation in Tub was excluded from 118 ethnically matched normal controls. Although minigen assay revealed that this variant of c.1379A>G in Tub did not affect normal splicing in vitro, multiple bioinformatic algorithm predicted that this variant was deleterious. Conclusions : For the first time we reported the identification of a rare homozygous mutant ( c.1379A>G: p.N460S) in Tub in a consanguineous family with arRP, which was probably the pathogenic basis of arRP in this consanguineous family.

Background Retinitis pigmentosa (RP) is the most common type of inherited retinopathy. At least 69 genes for RP have been identified. A significant proportion of RP, however, remains genetically unsolved. In this study, the genetic basis of a Chinese consanguineous family with presumed autosomal recessive retinitis pigmentosa (arRP) was investigated. Methods Overall ophthalmic examinations, including funduscopy, decimal best-corrected visual acuity, axial length and electroretinography (ERG) were performed for the family. Genomic DNA from peripheral blood of the proband was subjected to whole exome sequencing. In silico predictions, structural modelling, and minigene assays were conducted to evaluate the pathogenicity of the variant. Results A novel homozygous variant (NM_003320.4: c.1379A > G) in the TUB gene was identified as a candidate pathogenic variant in this parental consanguineous pedigree. This variant co-segregated with the disease in this pedigree and was absent in 118 ethnically matched healthy controls. It’s an extremely rare variant that is neither deposited in population databases (1000 Genomes, ExAC, GnomAD, or Exome Variant Server) nor reported in the literature. Phylogenetic analysis indicated that the Asn residue at codon 460 of TUB is highly conserved across diverse species from tropicalis to humans. It was also completely conserved among the TUB, TULP1, TULP2, and TULP3 family proteins. Multiple bioinformatic algorithms predicted that this variant was deleterious. Conclusions A novel missense variant in TUB was identified, which was probably the pathogenic basis for arRP in this consanguineous family. This is the first report of a homozygous missense variant in TUB for RP.

Background: Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies characterized by the primary degeneration of rod photoreceptors and the subsequent loss of cone photoreceptors because of cell death. It is caused by different mechanisms, including inflammation, apoptosis, necroptosis, pyroptosis, and autophagy. Variants in the usherin gene (USH2A) have been reported in autosomal recessive RP with or without hearing loss. In the present study, we aimed to identify causative variants in a Han-Chinese pedigree with autosomal recessive RP.Methods: A six-member, three-generation Han-Chinese family with autosomal recessive RP was recruited. A full clinical examination, whole exome sequencing, and Sanger sequencing, as well as co-segregation analysis were performed.Results: Three heterozygous variants in the USH2A gene, c.3304C>T (p.Q1102*), c.4745T>C (p.L1582P), and c.14740G>A (p.E4914K), were identified in the proband, which were inherited from parents and transmitted to the daughters. Bioinformatics analysis supported the pathogenicity of the c.3304C>T (p.Q1102*) and c.4745T>C (p.L1582P) variants.Conclusions: Novel compound heterozygous variants in the USH2A gene, c.3304C>T (p.Q1102*) and c.4745T>C (p.L1582P), were identified as the genetic causes of autosomal recessive RP. The findings may enhance the current knowledge of the pathogenesis of USH2A-associated phenotypes, expand the spectrum of the USH2A gene variants, and contribute to improved genetic counseling, prenatal diagnosis, and disease management.