tetano
Editor, Senior Moderator
Brief Bioinform
. 2020 Oct 2;bbaa233.
doi: 10.1093/bib/bbaa233. Online ahead of print.
Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity
Shaolei Teng[SUP] 1 [/SUP], Adebiyi Sobitan[SUP] 1 [/SUP], Raina Rhoades[SUP] 1 [/SUP], Dongxiao Liu[SUP] 2 [/SUP], Qiyi Tang[SUP] 2 [/SUP]
Affiliations
Abstract
The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the binding to the permissive cells. The receptor-binding domain (RBD) of SARS-CoV-2 S protein directly interacts with the human angiotensin-converting enzyme 2 (ACE2) on the host cell membrane. In this study, we used computational saturation mutagenesis approaches, including structure-based energy calculations and sequence-based pathogenicity predictions, to quantify the systemic effects of missense mutations on SARS-CoV-2 S protein structure and function. A total of 18 354 mutations in S protein were analyzed, and we discovered that most of these mutations could destabilize the entire S protein and its RBD. Specifically, residues G431 and S514 in SARS-CoV-2 RBD are important for S protein stability. We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein. Moreover, many mutations in N-linked glycosylation sites can increase the stability of the S protein. In addition, we investigated 3705 mutations in SARS-CoV-2 RBD and 11 324 mutations in human ACE2 and found that SARS-CoV-2 neighbor residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD-ACE2 interaction. The findings comprehensively provide potential target sites in the development of drugs and vaccines against COVID-19.
Keywords: COVID-19; RBD–ACE2 interaction; SARS-CoV-2 S stability; computational saturation mutagenesis; missense mutation.
. 2020 Oct 2;bbaa233.
doi: 10.1093/bib/bbaa233. Online ahead of print.
Systemic effects of missense mutations on SARS-CoV-2 spike glycoprotein stability and receptor-binding affinity
Shaolei Teng[SUP] 1 [/SUP], Adebiyi Sobitan[SUP] 1 [/SUP], Raina Rhoades[SUP] 1 [/SUP], Dongxiao Liu[SUP] 2 [/SUP], Qiyi Tang[SUP] 2 [/SUP]
Affiliations
- PMID: 33006605
- DOI: 10.1093/bib/bbaa233
Abstract
The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the binding to the permissive cells. The receptor-binding domain (RBD) of SARS-CoV-2 S protein directly interacts with the human angiotensin-converting enzyme 2 (ACE2) on the host cell membrane. In this study, we used computational saturation mutagenesis approaches, including structure-based energy calculations and sequence-based pathogenicity predictions, to quantify the systemic effects of missense mutations on SARS-CoV-2 S protein structure and function. A total of 18 354 mutations in S protein were analyzed, and we discovered that most of these mutations could destabilize the entire S protein and its RBD. Specifically, residues G431 and S514 in SARS-CoV-2 RBD are important for S protein stability. We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein. Moreover, many mutations in N-linked glycosylation sites can increase the stability of the S protein. In addition, we investigated 3705 mutations in SARS-CoV-2 RBD and 11 324 mutations in human ACE2 and found that SARS-CoV-2 neighbor residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD-ACE2 interaction. The findings comprehensively provide potential target sites in the development of drugs and vaccines against COVID-19.
Keywords: COVID-19; RBD–ACE2 interaction; SARS-CoV-2 S stability; computational saturation mutagenesis; missense mutation.