Minireview of progress in the structural study of SARS-CoV-2 proteins

Zhu, Guoliang; Zhu, Chunmei; Zhu, Yun; Sun, Fei

doi:10.1016/j.crmicr.2020.06.003

Cited by 44 publications

(61 citation statements)

References 105 publications

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“…The main emphasis here is on the development and application of protein side-chain network approaches (Bhattacharyya et al, 2016;Salamanca Viloria et al, 2017;Kayikci et al, 2018), which have been shown to capture subtle conformational differences that are sometimes elusive to conventional analyses, such as the root mean square deviation (RMSD) at the backbone level. Here, we have considered the SARS-CoV-2 Spike glycoprotein (Zhu et al, 2020) as an illustrative example to demonstrate the capabilities of side-chain network studies. Our focus on analyzing SARS-CoV-2 spike protein, in particular, stems from its critical role in COVID-19 and the immediacy posed by the global pandemic caused by this highly infectious coronavirus.…”

Section: Introductionmentioning

confidence: 99%

“…To develop promising therapeutic strategies, we need a clear understanding of the mechanism of action of the SARS-CoV-2 virus. A succinct summary of the structures of the SARS-CoV-2 spike protein and its interactions with the host cell membrane has been recently provided (Wang et al, 2020b;Xia et al, 2020a;Zhu et al, 2020). These studies highlight how the recognition of the human ACE2 receptor by the spike protein mediates viral entry into the host cell.…”

Section: Introductionmentioning

confidence: 99%

“…In this article, we have selected the closed (PDB_ID: 6VXX) and partially open (PDB_ID: 6VYB) structures of the spike protein (Walls et al, 2020) as examples to explicitly elucidate the protein side-chain network concepts. Each subunit in the spike protein is organized into an S1 and S2 domain (Figures 2A,B) (Xia et al, 2020a;Zhu et al, 2020). The S1 domain hosts the receptor-binding domain (RBD) that recognizes the human ACE2 receptor (Figures 2A,B) and the Nterminal domain (NTD).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Surveying the Side-Chain Network Approach to Protein Structure and Dynamics: The SARS-CoV-2 Spike Protein as an Illustrative Case

Halder

Anto

Subramanyan

et al. 2020

Front. Mol. Biosci.

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Network theory-based approaches provide valuable insights into the variations in global structural connectivity between different dynamical states of proteins. Our objective is to review network-based analyses to elucidate such variations, especially in the context of subtle conformational changes. We present technical details of the construction and analyses of protein structure networks, encompassing both the non-covalent connectivity and dynamics. We examine the selection of optimal criteria for connectivity based on the physical concept of percolation. We highlight the advantages of using side-chain-based network metrics in contrast to backbone measurements. As an illustrative example, we apply the described network approach to investigate the global conformational changes between the closed and partially open states of the SARS-CoV-2 spike protein. These conformational changes in the spike protein is crucial for coronavirus entry and fusion into human cells. Our analysis reveals global structural reorientations between the two states of the spike protein despite small changes between the two states at the backbone level. We also observe some differences at strategic locations in the structures, correlating with their functions, asserting the advantages of the side-chain network analysis. Finally, we present a view of allostery as a subtle synergistic-global change between the ligand and the receptor, the incorporation of which would enhance drug design strategies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Surveying the Side-Chain Network Approach to Protein Structure and Dynamics: The SARS-CoV-2 Spike Protein as an Illustrative Case

Halder

Anto

Subramanyan

et al. 2020

Front. Mol. Biosci.

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“…In tissues that express the necessary entry receptors and proteases, membrane fusion is followed by release of the nucleocapsid into the cytoplasm, where it disassembles and exposes a ~30 kb RNA strand that encodes the 4 structural proteins, 16 non-structural proteins (NSPs) and 9 accessory proteins ( Figure 2 ). Gene 1, which occupies approximately two-third of the viral genome, is translated by host-cell ribosomes into two overlapping replicase polyproteins (pp1a and pp1ab), which are cleaved into the 16 NSPs by two virally encoded cysteine proteases [ 21 , 22 ]. Viral 3-chymotrypsin-like protease (3CLpro or Mpro, NSP5) is the main protease and responsible for processing 11 restriction sites (including its autolytic cleavage site) on the pp1ab protein [ 21 , 22 , 23 ].…”

Section: Sars-cov-2 Structure Infection Replication and Treatmenmentioning

confidence: 99%

“…Gene 1, which occupies approximately two-third of the viral genome, is translated by host-cell ribosomes into two overlapping replicase polyproteins (pp1a and pp1ab), which are cleaved into the 16 NSPs by two virally encoded cysteine proteases [ 21 , 22 ]. Viral 3-chymotrypsin-like protease (3CLpro or Mpro, NSP5) is the main protease and responsible for processing 11 restriction sites (including its autolytic cleavage site) on the pp1ab protein [ 21 , 22 , 23 ]. The remaining three restriction sites are cleaved by viral papain-like protease (PLpro, NSP3), which is also involved in the evasion of host antiviral immune responses [ 21 , 24 ].…”

Section: Sars-cov-2 Structure Infection Replication and Treatmenmentioning

confidence: 99%

Nuclear Medicine in Times of COVID-19: How Radiopharmaceuticals Could Help to Fight the Current and Future Pandemics

2020

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The emergence and global spread of COVID-19, an infectious disease caused by the novel coronavirus SARS-CoV-2, has resulted in a continuing pandemic threat to global health. Nuclear medicine techniques can be used for functional imaging of (patho)physiological processes at the cellular or molecular level and for treatment approaches based on targeted delivery of therapeutic radionuclides. Ongoing development of radiolabeling methods has significantly improved the accessibility of radiopharmaceuticals for in vivo molecular imaging or targeted radionuclide therapy, but their use for biosafety threats such as SARS-CoV-2 is restricted by the contagious nature of these agents. Here, we highlight several potential uses of nuclear medicine in the context of SARS-CoV-2 and COVID-19, many of which could also be performed in laboratories without dedicated containment measures. In addition, we provide a broad overview of experimental or repurposed SARS-CoV-2-targeting drugs and describe how radiolabeled analogs of these compounds could facilitate antiviral drug development and translation to the clinic, reduce the incidence of late-stage failures and possibly provide the basis for radionuclide-based treatment strategies. Based on the continuing threat by emerging coronaviruses and other pathogens, it is anticipated that these applications of nuclear medicine will become a more important part of future antiviral drug development and treatment.

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Synthesis and Applications of Peptides and Peptidomimetics in Drug Discovery

JIMMIDI

2023

Eur J Org Chem

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Peptides are described as naturally occurring short chains of amino acids and offer great potential as therapeutic agents because of their target selectivity, safe, and well tolerable. Hence, there is an increased interest in peptides in pharmaceutical research and development and approximately more than 170 peptide therapeutics are currently being evaluated in clinical trials and many are being used as therapeutic drugs for various diseases including COVID‐19. The present Review article focuses on recent progress in peptide drug discovery and advancements in synthetic methodologies to enhance their stability and physiological activity of peptides and as well peptidomimetics.

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Minireview of progress in the structural study of SARS-CoV-2 proteins

Cited by 44 publications

References 105 publications

Surveying the Side-Chain Network Approach to Protein Structure and Dynamics: The SARS-CoV-2 Spike Protein as an Illustrative Case

Surveying the Side-Chain Network Approach to Protein Structure and Dynamics: The SARS-CoV-2 Spike Protein as an Illustrative Case

Nuclear Medicine in Times of COVID-19: How Radiopharmaceuticals Could Help to Fight the Current and Future Pandemics

Synthesis and Applications of Peptides and Peptidomimetics in Drug Discovery

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