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Population-Specific ACE2 Single-Nucleotide Polymorphisms Have Limited Impact on SARS-CoV-2 Infectivity In Vitro.
Hashizume, Mei; Gonzalez, Gabriel; Ono, Chikako; Takashima, Ayako; Iwasaki, Masaharu.
  • Hashizume M; Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Osaka 565-0871, Japan.
  • Gonzalez G; UCD National Virus Reference Laboratory, Belfield Campus, Dublin 4, Ireland.
  • Ono C; Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Osaka 565-0871, Japan.
  • Takashima A; Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Osaka 565-0871, Japan.
  • Iwasaki M; Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Osaka 565-0871, Japan.
Viruses ; 13(1)2021 Jan 06.
Article in English | MEDLINE | ID: covidwho-1011630
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), employs host-cell angiotensin-converting enzyme 2 (ACE2) for cell entry. Genetic analyses of ACE2 have identified several single-nucleotide polymorphisms (SNPs) specific to different human populations. Molecular dynamics simulations have indicated that several of these SNPs could affect interactions between SARS-CoV-2 and ACE2, thereby providing a partial explanation for the regional differences observed in SARS-CoV-2 infectivity and severity. However, the significance of population-specific ACE2 SNPs in SARS-CoV-2 infectivity is unknown, as no in vitro validation studies have been performed. Here, we analyzed the impact of eight SNPs found in specific populations on receptor binding and cell entry in vitro. Except for a SNP causing a nonsense mutation that reduced ACE2 expression, none of the selected SNPs markedly altered the interaction between ACE2 and the SARS-CoV-2 spike protein (SARS-2-S), which is responsible for receptor recognition and cell entry, or the efficiency of viral cell entry mediated by SARS-2-S. Our findings indicate that ACE2 polymorphisms have limited impact on the ACE2-dependent cell entry of SARS-CoV-2 and underscore the importance of future studies on the involvement of population-specific SNPs of other host genes in susceptibility toward SARS-CoV-2 infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Virus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13010067

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Virus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13010067