Structural insights into SARS-CoV-2 infection and therapeutics development

Sun, Gangyu; Xue, Lu‐Lu; He, Qingjing; Zhao, Yue; Xu, Wenqing; Wang, Zhizhi

doi:10.1016/j.scr.2021.102219

Cited by 12 publications

(7 citation statements)

References 127 publications

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“…The S1 subunit binds to the cell receptor and is subdivided into four domains: N-terminal domain (NTD) (aa 13–306), receptor-binding domain (RBD) (aa 319–541), C-terminal domain 1 (CTD1) and C-terminal domain 2 (CTD2). The S2 subunit mediates membrane fusion and contains fusion peptide (FP), heptad repeat 1 (HR1) (aa 920–970), central helix (CH) (aa 971–1035), connector domain (CD), heptad repeat 2 (HR2) (aa 1,163–1,202), transmembrane domain (TM) and C-terminal domain (CT) ( Sun et al, 2021 ; Figures 1A,B ).…”

Section: Resultsmentioning

confidence: 99%

“…Coronaviruses’ amino acid sequences are highlighted in bold and colored corresponding to the (A–C) ; glycine-serine linker within PE protein and (His) 6 -tags are italicized; amino acid residues encoded by restriction sites used for cloning ( Bam HI, Hin dIII, Sal I) are underlined; sequences encoded by the pQE30 vector, including the polylinker fragments, are shown with normal font. Domains are colored according to the coordinates indicated in Sun et al (2021) .…”

Section: Resultsmentioning

confidence: 99%

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Vaccine Candidate Against COVID-19 Based on Structurally Modified Plant Virus as an Adjuvant

et al. 2022

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A recombinant vaccine candidate has been developed based on the major coronaviruses’ antigen (S protein) fragments and a novel adjuvant—spherical particles (SPs) formed during tobacco mosaic virus thermal remodeling. The receptor-binding domain and the highly conserved antigenic fragments of the S2 protein subunit were chosen for the design of recombinant coronavirus antigens. The set of three antigens (Co1, CoF, and PE) was developed and used to create a vaccine candidate composed of antigens and SPs (SPs + 3AG). Recognition of SPs + 3AG compositions by commercially available antibodies against spike proteins of SARS-CoV and SARS-CoV-2 was confirmed. The immunogenicity testing of these compositions in a mouse model showed that SPs improved immune response to the CoF and PE antigens. Total IgG titers against both proteins were 9–16 times higher than those to SPs. Neutralizing activity against SARS-CoV-2 in serum samples collected from hamsters immunized with the SPs + 3AG was demonstrated.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Vaccine Candidate Against COVID-19 Based on Structurally Modified Plant Virus as an Adjuvant

et al. 2022

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“…Papain-like protease (PLpro), encoded by NSP3, recognizes the LXGG tetrapeptide motif found in-between viral proteins nsp1 and nsp2, nsp2 and nsp3, and processes the replicase polyprotein 1a (pp1a) and replicase polyprotein 1ab (pp1ab) on the N-termini into nsp1, nsp2, and nsp3, essential for viral replication. [7,8] PLpro is a monomer with an active site that comprises a Cys111/His272/Asp286 canonical catalytic triad. The SARS-CoV-2 PLpro modulates the host immune system via deubiquitination and deISGylation from the host cell proteins resulting in inhibition of the host antiviral innate immune response.…”

Section: Introductionmentioning

confidence: 99%

Identification of SARS‐CoV‐2 Papain‐like Protease (PLpro) Inhibitors Using Combined Computational Approach**

et al. 2022

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In the current pandemic, finding an effective drug to prevent or treat the infection is the highest priority. A rapid and safe approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 PLpro promotes viral replication and modulates the host immune system, resulting in inhibition of the host antiviral innate immune response, and therefore is an attractive drug target. In this study, we used a combined in silico virtual screening for candidates for SARS-CoV-2 PLpro protease inhibitors. We used the Informational spectrum method applied for Small Molecules for searching the Drugbank database followed by molecular docking. After in silico screening of drug space, we identified 44 drugs as potential SARS-CoV-2 PLpro inhibitors that we propose for further experimental testing.

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“…[3][4][5][6] The processing of two large viral polyproteins is autocatalytic proteolysis processed by virally encoded cysteine proteases. Papain-like protease (PLpro), encoded by NSP3, recognizes the LXGG tetrapeptide motif found in-between viral proteins nsp1 and nsp2, nsp2 and nsp3, and processes the replicase polyprotein 1a (pp1a) and replicase polyprotein 1ab (pp1ab) on the N-termini into nsp1, nsp2, and nsp3, essential for viral replication [7,8]. PLP is a monomer with an active site that comprises a Cys111/His272/Asp286 canonical catalytic triad.…”

Section: Introductionmentioning

confidence: 99%

Drug Repurposing for Candidate SARS-CoV-2 Papain-like protease (PLpro) Inhibitors by a combined in Silico Method

Senćanski

Perović

Мilićević

et al. 2021

Preprint

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The need for an effective drug against COVID-19, is, after almost 18 months since the global pandemics outburst, still very high. A very quick and safe approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 PLpro promotes vi-ral replication and modulates the host immune system, resulting in inhibition of the host antiviral innate immune response, and there-fore is an attractive drug target. In this study, we used a combined in silico virtual screening candidates for SARS-CoV-2 PLpro protease inhibitors. We used the Informational spectrum method applied for Small Molecules for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 44 drugs as potential SARS-CoV-2 PLpro inhibitors that we propose for further experimental testing.

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Structural insights into SARS-CoV-2 infection and therapeutics development

Cited by 12 publications

References 127 publications

Vaccine Candidate Against COVID-19 Based on Structurally Modified Plant Virus as an Adjuvant

Vaccine Candidate Against COVID-19 Based on Structurally Modified Plant Virus as an Adjuvant

Identification of SARS‐CoV‐2 Papain‐like Protease (PLpro) Inhibitors Using Combined Computational Approach**

Drug Repurposing for Candidate SARS-CoV-2 Papain-like protease (PLpro) Inhibitors by a combined in Silico Method

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