Structural biology of SARS-CoV-2 and implications for therapeutic development

Yang, Haitao; Rao, Zihe

doi:10.1038/s41579-021-00630-8

Cited by 345 publications

(362 citation statements)

References 160 publications

(117 reference statements)

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“…The S protein is a surface-located trimeric glycoprotein of coronaviruses that promotes the attachment of viruses to the host cells through binding to angiotensin-converting enzyme 2 (ACE2) and virus-cell membrane fusion during viral infection. Thus, the S protein has been considered a significant target for developing vaccines and therapeutics against SARS-CoV-2 [12,13].…”

Section: Drug Targets Of Covid-19mentioning

confidence: 99%

“…Thus, it can be regarded as a viral suppressor of RNA silencing. The N protein is potentially a target for vaccine development because it induces severe immune responses during infection [12].…”

Section: Nucleocapsid (N) Proteinmentioning

confidence: 99%

“…Compared with other coronaviruses, the N protein from SARS-CoV-2 displays different charge distributions in the N-terminal loop, the RNA protruding tip, the bottom of the N-NTD core, and the N-CTD β-strand face. Hence, the variations in RNA binding to the N protein may further guide inhibitor optimization [12].…”

Section: Nucleocapsid (N) Proteinmentioning

confidence: 99%

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A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

Khataniar

Pathak

Rajkhowa

et al. 2022

COVID

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Drug repurposing is a more inexpensive and shorter approach than the traditional drug discovery and development process. The concept of identifying a potent molecule from a library of pre-existing molecules or an already approved drug has become a go-to tactic to accelerate the identification of drugs that can prevent COVID-19. This seemingly uncontrollable disease is caused by SARS-CoV-2. It is a novel virus of the Betacoronavirus genus, exhibiting similarities to the previously reported SAR-CoV genome structure and viral pathogenesis. The emergence of SARS-CoV-2 and the rapid outbreak of COVID-19 have resulted in a global pandemic. Researchers are hard-pressed to develop new drugs for total containment of the disease, thus making the cost-effective drug repurposing a much more feasible approach. Therefore, the current review attempts to collate both the experimental and computational drug repurposing strategies that have been utilized against significant drug targets of SARS-CoV-2. Along with the strategies, the available druggable targets shall also be discussed. However, the occurrence of frequent recombination of the viral genome and time-bound primary analysis, resulting in insignificant data, are two major challenges that drug repurposing still faces.

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Section: Drug Targets Of Covid-19mentioning

confidence: 99%

Section: Nucleocapsid (N) Proteinmentioning

confidence: 99%

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A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

Khataniar

Pathak

Rajkhowa

et al. 2022

COVID

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“…This coronavirus is made of sixteen non-structural proteins and four structural proteins. The non-structural proteins are involved mainly in virus replication [ 1 , 2 ]. The structural proteins, including the membrane (M), nucleocapsid (N), envelope (E) and spike (S) proteins, are implied in the assembly and infection of the virus [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-SARS-CoV-2 Omicron Antibodies Isolated from a SARS-CoV-2 Delta Semi-Immune Phage Display Library

et al. 2022

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This report describes the discovery and characterization of antibodies with potential broad SARS-CoV-2 neutralization profiles. The antibodies were obtained from a phage display library built with the VH repertoire of a convalescent COVID-19 patient who was infected with SARS-CoV-2 B.1.617.2 (Delta). The patient received a single dose of Ad5-nCoV vaccine (Convidecia™, CanSino Biologics Inc.) one month before developing COVID-19 symptoms. Four synthetic VL libraries were used as counterparts of the immune VH repertoire. After three rounds of panning with SARS-CoV-2 receptor-binding domain wildtype (RBD-WT) 34 unique scFvs, were identified, with 27 cross-reactive for the RBD-WT and RBD Delta (RBD-DT), and seven specifics for the RBD-WT. The cross-reactive scFvs were more diverse than the RBD-WT specific ones, being encoded by several IGHV genes from the IGHV1 and IGHV3 families combined with short HCDR3s. Six cross-reactive scFvs and one RBD-WT specific scFv were converted to human IgG1 (hIgG1). Out of the seven antibodies, six blocked the RBD-WT binding to angiotensin converting enzyme 2 (ACE2), suggesting these antibodies may neutralize the SARS-CoV-2 infection. Importantly, one of the antibodies also recognized the RBD from the B.1.1.529 (Omicron) isolate, implying that the VH repertoire of the convalescent patient would protect against SARS-CoV-2 Wildtype, Delta, and Omicron. From a practical viewpoint, the triple cross-reactive antibody provides the substrate for developing therapeutic antibodies with a broad SARS-CoV-2 neutralization profile.

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“…Among them, the replicase gene (ORF 1ab) encodes for the two overlapping polyproteins pp1a and pp1ab, which are cleaved by the main protease (M pro , also referred to as 3CL pro ) ( Fig. 1 ) ( Ullrich and Nitsche, 2020 ; Yang and Rao, 2021 ). This is a key step in the process of virus replication, transcription, and maturation ( Du et al, 2004 ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of RevX solution extract as a potential inhibitor of the main protease of SARS-CoV-2—In vitro study and molecular docking

Chou

Liu

Giang

et al. 2022

Heliyon

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Structural biology of SARS-CoV-2 and implications for therapeutic development

Cited by 345 publications

References 160 publications

A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

Anti-SARS-CoV-2 Omicron Antibodies Isolated from a SARS-CoV-2 Delta Semi-Immune Phage Display Library

Evaluation of RevX solution extract as a potential inhibitor of the main protease of SARS-CoV-2—In vitro study and molecular docking

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